FBrf0090846 96321106 8755038 1996 11 22 1996 11 22 2000 12 18

0016-6758 32 5 1996 May [Effect of genetic background on mutation frequency of insertional alleles of the lozenge in Drosophila melanogaster] 641-8 We studied the effect of genetic background on mutation frequency of an unstable lz75V allele of the lozenge gene (lz; 1-27.7) isolated from natural populations of Drosophila melanogaster and its mutant derivatives lzB abd lzsl. Genetic composition of the X chromosome containing unstable alleles (X75V chromosome) was shown to affect their mutability. The region of the chromosome proximal to lozenge contains factors required for high mutability of lz75V and lzB. Substitution of a distal part of the X chromosome from a laboratory strain for a homologous part of the X75V chromosome also resulted in stabilizing lz75V, but caused an increase in mutation frequency of lzB. Association between instability of lz75V and the presence of P element with the locus was revealed by in situ hybridization. Studying effects of regulatory elements from a pi 2 P strain showed that the P cytotype is associated with a twofold to threefold decrease in mutation frequency of lzB and lzsl, but P-M hybrid dysgenesis is associated with its slight increase. Regulation of instability of the lozenge gene within the X75V chromosome was assumed to involve three levels: (1) character and topography of a mobile element inserted into the locus, (2) regulatory factors of other X-chromosomal regions, and (3) cytoplasmic factors. The results obtained are discussed in terms of regulation of transposition of mobile genetic elements. Voloshina M A MA Golubovskiĭ M D MD Pavlova M B MB Beliaeva E S ES rus Journal Article Vliianie geneticheskogo fona na chastotu mutirovaniia insertsionnykh allelĭ gena lozenge u Drosophila melanogaster.

RUSSIA Genetika 0047354 0 DNA Transposable Elements IM Alleles Animal Chromosomes Cytoplasm physiology DNA Transposable Elements Drosophila melanogaster genetics English Abstract Gene Expression Regulation physiology Genes, Insect Mutagenesis, Insertional physiology FBrf0109184 99307078 10375505 1999 08 19 1999 08 19 2003 03 28

0950-1991 126 14 1999 Jun Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors. 3149-57 The selection of Drosophila melanogaster sense organ precursors (SOPs) for sensory bristles is a progressive process: each neural equivalence group is transiently defined by the expression of proneural genes (proneural cluster), and neural fate is refined to single cells by Notch-Delta lateral inhibitory signalling between the cells. Unlike sensory bristles, SOPs of chordotonal (stretch receptor) sense organs are tightly clustered. Here we show that for one large adult chordotonal SOP array, clustering results from the progressive accumulation of a large number of SOPs from a persistent proneural cluster. This is achieved by a novel interplay of inductive epidermal growth factor-receptor (EGFR) and competitive Notch signals. EGFR acts in opposition to Notch signalling in two ways: it promotes continuous SOP recruitment despite lateral inhibition, and it attenuates the effect of lateral inhibition on the proneural cluster equivalence group, thus maintaining the persistent proneural cluster. SOP recruitment is reiterative because the inductive signal comes from previously recruited SOPs. Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3JR, UK. zur Lage P P Jarman A P AP eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Membrane Proteins 0 Rho protein, Drosophila 0 ato protein 0 notch protein 0 rho-2 protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal DNA-Binding Proteins genetics metabolism Drosophila genetics growth & development Extremities growth & development Gene Expression Regulation, Developmental Larva Membrane Proteins genetics metabolism Neurons metabolism Receptor, Epidermal Growth Factor genetics metabolism Sense Organs growth & development innervation metabolism Signal Transduction Support, Non-U.S. Gov't FBrf0099019 98033250 9367427 1997 12 11 1997 12 11 2000 12 18

0950-1991 124 19 1997 Oct Control of cell fate and polarity in the adult abdominal segments of Drosophila by optomotor-blind. 3715-26 In an accompanying report (Kopp, A., Muskavitch, M. A. T. and Duncan, I. (1997) Development 124, 3703-3714), we show that Hh protein secreted by posterior compartment cells patterns the posterior portion of the anterior compartment in adult abdominal segments. Here we show that this function of hh is mediated by optomotor-blind (omb). omb- mutants mimic the effects of loss-of-function alleles of hh: structures from the posterior of the anterior compartment are lost, and often this region develops as a mirror image of the anterior portion. Structures from the anterior part of the posterior compartment are also lost. In the pupa, omb expression in abdominal histoblasts is highest at or near the compartment boundary, and decreases in a shallow gradient toward the anterior. This gradient is due to activation of omb by Hh secreted by posterior compartment cells. In contrast to imaginal discs, this Hh signaling is not mediated by dpp or wg. We describe several gain-of-function alleles that cause ectopic expression of omb in the anterior of the segment. Most of these cause the anterior region to develop with posterior characteristics without affecting polarity. However, an allele that drives high level ubiquitous expression of omb (QdFab) causes the anterior tergite to develop as a mirror-image duplication of the posterior tergite, a pattern opposite to that seen in omb- mutants. Ubiquitous expression of hh causes similar double-posterior patterning. We find that omb- alleles suppress this effect of ectopic hh expression and that posterior patterning becomes independent of hh in the QdFab mutant. These observations indicate that omb is the primary target of hh signaling in the adult abdomen. However, it is clear that other targets exist. One of these is likely Scruffy, a novel gene that we describe, which acts in parallel to omb. To explain the effects of omb alleles, we propose that both anterior and posterior compartments in the abdomen are polarized by underlying symmetric gradients of unknown origin. We suggest that omb has two functions. First, it specifies the development of appropriate structures both anterior and posterior to the compartment boundary. Second, it causes cells to reverse their interpretation of polarity specified by the underlying symmetric gradients. Department of Biology, Washington University, St Louis, MO 63130, USA. Kopp A A Duncan I I eng GM32318 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Nerve Tissue Proteins 146635-31-6 omb protein, Drosophila IM Abdomen Alleles Animal Body Patterning Cell Lineage genetics Cell Polarity genetics DNA-Binding Proteins biosynthesis genetics physiology Drosophila melanogaster cytology genetics physiology Genes, Dominant Genes, Insect Mutation Nerve Tissue Proteins biosynthesis genetics physiology Phenotype Pupa Support, U.S. Gov't, P.H.S. FBrf0059082 93287994 8510653 1993 07 15 1993 07 15 2000 12 18

0026-8925 239 1-2 1993 May Genetic analysis of the X-chromosomal region 1E-2A of Drosophila melanogaster. 257-68 Reversion mutagenesis of three single P elements located in the cytogenetic interval 1E-2A at the tip of the X chromosome of Drosophila melanogaster was used to recover new deletions in this chromosomal region. The deletions obtained include small aberrations within region 2A and larger lesions extending from 2A into 1E and 1B. All three screens also yielded terminal deficiencies. The new deficiencies, together with previously characterized rearrangements, were analyzed for their complementation behaviour with the maternal effect locus fs(1) Nasrat and lethal loci in the region. These analyses provide an overall genetic map of the interval 1E-2A. In addition, the smaller deletions were physically mapped within cloned genomic DNA of the 2A region. Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Germany. Degelmann A A eng Journal Article

GERMANY Mol Gen Genet 0125036 IM Animal Chromosome Mapping Drosophila melanogaster embryology genetics Female Genes, Lethal Genetic Complementation Test In Situ Hybridization Male Mutagenesis Phenotype Restriction Mapping Support, Non-U.S. Gov't Transformation, Genetic X Chromosome FBrf0073171 94254814 8196601 1994 06 24 1994 06 24 2002 04 19

0270-7306 14 6 1994 Jun Dorsal, a Drosophila Rel-like protein, is phosphorylated upon activation of the transmembrane protein Toll. 3559-68 The nuclear import of dorsal, a Drosophila Rel homolog, is directed by a spatially restricted extracellular ligand in blastoderm embryos. We have demonstrated both that dorsal is an embryonic phosphoprotein and that its phosphorylation state is regulated by an intracellular signaling pathway initiated by the transmembrane receptor Toll. Immunoblot analysis of cytoplasm from precisely staged embryos revealed that the phosphorylation state of dorsal is altered during the time period that Toll is activated. Moreover, mutations that constitutively activate Toll stimulated dorsal phosphorylation, while mutations that block Toll activation reduced the level of dorsal phosphorylation. We further demonstrated that signal-dependent dorsal phosphorylation is modulated by three intracellular proteins, pelle, tube, and cactus. Using double-mutant embryos, we then explored the nature of the kinase activity responsible for dorsal phosphorylation. We found that free dorsal is a substrate for a signal-independent kinase activity. In addition, our results imply that dorsal is a substrate for a Toll-dependent kinase. These results are consistent with the hypothesis that phosphorylation of Rel-related proteins may be required for the proper nuclear localization and transcriptional activity of these proteins. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038. Gillespie S K SK Wasserman S A SA eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Insect Hormones 0 Membrane Glycoproteins 0 Nuclear Proteins 0 Phosphoproteins 0 Receptors, Cell Surface 0 dorsal protein, Drosophila 1114-81-4 Phosphothreonine 118929-01-4 Toll protein, Drosophila 17885-08-4 Phosphoserine IM Animal Blastoderm metabolism Cell Membrane metabolism Cell Nucleus metabolism Drosophila melanogaster embryology genetics metabolism Embryo, Nonmammalian metabolism Insect Hormones metabolism Membrane Glycoproteins metabolism Nuclear Proteins biosynthesis isolation & purification metabolism Phosphoproteins biosynthesis isolation & purification metabolism Phosphorylation Phosphoserine analysis Phosphothreonine analysis Protein Processing, Post-Translational Receptors, Cell Surface metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0139607 21479118 11595182 2001 10 11 2001 12 04 2003 06 16

0092-8674 107 1 2001 Oct 5 Guidance of cell migration by the Drosophila PDGF/VEGF receptor. 17-26 Directed cell migrations are important for development, but the signaling pathways and mechanisms responsible for guiding cell migration in vivo are poorly understood. Migration of border cells during Drosophila oogenesis is a simple and attractive model system in which to address these questions. We demonstrate that PVR, a receptor tyrosine kinase related to mammalian PDGF and VEGF receptors, acts in border cells to guide them to the oocyte. The oocyte is the source of a ligand for PVR, PDGF/VEGF factor 1 (PVF1). Intriguingly, the guidance function of PVR is largely redundant with that of EGFR. We present evidence implicating Rac and the Rac activator Mbc/DOCK180/CED-5 as mediators of the guidance signal. European Molecular Biology Laboratory, Developmental Biology Programme, 69117 Heidelberg, Germany. Duchek P P Somogyi K K Jékely G G Beccari S S Rørth P P eng Journal Article

United States Cell 0413066 0 Actins 0 Egg Proteins 0 Insect Proteins 0 Ligands 0 PDGF-VEGF factor 1 0 Receptors, Growth Factor 0 myoblast city protein, Drosophila EC 2.7.1.112 PDGF-VEGF receptor, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.112 Receptors, Platelet-Derived Growth Factor EC 2.7.1.112 Receptors, Vascular Endothelial Growth Factor EC 3.6.1.- rac GTP-Binding Proteins IM Actins metabolism Amino Acid Sequence Animal Cell Movement physiology Cytoskeleton metabolism Drosophila melanogaster cytology physiology Egg Proteins chemistry genetics metabolism Female Human Immunoblotting Insect Proteins chemistry genetics metabolism Ligands Microscopy, Fluorescence Molecular Sequence Data Oocytes cytology physiology Oogenesis physiology Ovary metabolism Receptor Protein-Tyrosine Kinases metabolism Receptor, Epidermal Growth Factor metabolism Receptors, Growth Factor metabolism Receptors, Platelet-Derived Growth Factor metabolism Receptors, Vascular Endothelial Growth Factor Sequence Alignment Signal Transduction physiology rac GTP-Binding Proteins metabolism FBrf0054663 91172174 1900919 1991 04 22 1991 04 22 2000 12 18

0270-7306 11 4 1991 Apr Repression of hsp70 heat shock gene transcription by the suppressor of hairy-wing protein of Drosophila melanogaster. 1894-900 The suppressor of hairy-wing [su(Hw)] locus of Drosophila melanogaster encodes a zinc finger protein that binds a repeated motif in the gypsy retroposon. Mutations of su(Hw) suppress the phenotypes associated with mutations caused by gypsy insertions. To examine the mechanisms by which su(Hw) alters gene expression, a fragment of gypsy containing multiple su(Hw) protein-binding sites was inserted into various locations in the well-characterized Drosophila hsp70 heat shock gene promoter. We found no evidence for activation of basal hsp70 transcription by su(Hw) protein in cultured Drosophila cells but observed that it can repress heat shock-induced transcription. Repression occurred only when su(Hw) protein-binding sites were positioned between binding sites for proteins required for heat shock transcription. We propose that su(Hw) protein interferes nonspecifically with protein-protein interactions required for heat shock transcription, perhaps sterically, or by altering the ability of DNA to bend or twist. Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021. Holdridge C C Dorsett D D eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Heat-Shock Proteins 0 Insect Hormones 0 Transcription Factors 127385-83-5 hairy protein, insect IM hsp70 Alleles Amino Acid Sequence Animal Binding Sites Blotting, Northern Cell Line Drosophila melanogaster genetics Gene Expression Regulation Genes Heat-Shock Proteins genetics Insect Hormones genetics Molecular Sequence Data Mutation Phenotype Support, Non-U.S. Gov't Suppression, Genetic Transcription Factors genetics Transcription, Genetic Zinc Fingers genetics FBrf0106478 99147028 10022880 1999 03 25 1999 03 25 2001 11 02

0270-7306 19 3 1999 Mar Control of growth and differentiation by Drosophila RasGAP, a homolog of p120 Ras-GTPase-activating protein. 1928-37 Mammalian Ras GTPase-activating protein (GAP), p120 Ras-GAP, has been implicated as both a downregulator and effector of Ras proteins, but its precise role in Ras-mediated signal transduction pathways is unclear. To begin a genetic analysis of the role of p120 Ras-GAP we identified a homolog from the fruit fly Drosophila melanogaster through its ability to complement the sterility of a Schizosaccharomyces pombe (fission yeast) gap1 mutant strain. Like its mammalian homolog, Drosophila RasGAP stimulated the intrinsic GTPase activity of normal mammalian H-Ras but not that of the oncogenic Val12 mutant. RasGAP was tyrosine phosphorylated in embryos and its Src homology 2 (SH2) domains could bind in vitro to a small number of tyrosine-phosphorylated proteins expressed at various developmental stages. Ectopic expression of RasGAP in the wing imaginal disc reduced the size of the adult wing by up to 45% and suppressed ectopic wing vein formation caused by expression of activated forms of Breathless and Heartless, two Drosophila receptor tyrosine kinases of the fibroblast growth factor receptor family. The in vivo effects of RasGAP overexpression required intact SH2 domains, indicating that intracellular localization of RasGAP through SH2-phosphotyrosine interactions is important for its activity. These results show that RasGAP can function as an inhibitor of signaling pathways mediated by Ras and receptor tyrosine kinases in vivo. Genetic interactions, however, suggested a Ras-independent role for RasGAP in the regulation of growth. The system described here should enable genetic screens to be performed to identify regulators and effectors of p120 Ras-GAP. Cancer Research Campaign Center for Cell and Molecular Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom. Feldmann P P Eicher E N EN Leevers S J SJ Hafen E E Hughes D A DA eng GENBANK AJ012609 Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA, Complementary 0 GTPase-Activating Proteins 0 Proteins 0 ras GTPase-Activating Proteins EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 3.6.1.- GTP Phosphohydrolases EC 3.6.1.- ras Proteins IM Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA, Complementary Down-Regulation Drosophila melanogaster growth & development GTP Phosphohydrolases physiology GTPase-Activating Proteins Gene Expression Molecular Sequence Data Proteins genetics physiology Receptor Protein-Tyrosine Kinases metabolism Schizosaccharomyces Signal Transduction Support, Non-U.S. Gov't Wing ras GTPase-Activating Proteins ras Proteins genetics physiology FBrf0107294 99026067 9806926 1999 03 18 1999 03 18 2003 03 28

0950-1991 125 23 1998 Dec Regulation of EGF receptor signaling establishes pattern across the developing Drosophila retina. 4777-90 Developing epithelia use a variety of patterning mechanisms to place individual cells into their correct positions. However, the means by which pattern elements are established are poorly understood. Here, we report evidence that regulation of Drosophila EGF receptor (DER) activity plays a central role in propagating the evenly spaced array of ommatidia across the developing Drosophila retina. DER activity is essential for establishing the first ommatidial cell fate, the R8 photoreceptor neuron. R8s in turn appear to signal through Rhomboid and Vein to create a patterned array of 'proneural clusters' which contain high levels of phosphorylated ERKA and the bHLH protein Atonal. Finally, secretion by the proneural clusters of Argos represses DER activity in less mature regions to create a new pattern of R8s. Propagation of this process anteriorly results in a retina with a precise array of maturing ommatidia. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Campus Box 8103, St. Louis, Mo 63110, USA. Spencer S A SA Powell P A PA Miller D T DT Cagan R L RL eng NIH-1R01EY10717 EY NEI NO1-HD-2-3144 HD NICHD Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Membrane Proteins 0 Rho protein, Drosophila 0 Transcription Factors 0 basic helix-loop-helix protein EC2 0 rho-2 protein, Drosophila 182299-68-9 vein protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Body Patterning physiology DNA-Binding Proteins metabolism Drosophila melanogaster embryology genetics radiation effects Embryo, Nonmammalian physiology Gamma Rays Gene Expression Regulation, Developmental Genes, ras Helix-Loop-Helix Motifs Insect Proteins metabolism Membrane Proteins metabolism Mitosis Mutagenesis Phosphorylation Photoreceptors cytology embryology Pigment Epithelium of Eye cytology embryology Receptor, Epidermal Growth Factor genetics physiology Recombination, Genetic Retina cytology embryology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors metabolism FBrf0151439 22144535 12134163 2002 07 31 2002 09 11 2003 06 16

1465-7392 4 8 2002 Aug Kinesin I-dependent cortical exclusion restricts pole plasm to the oocyte posterior. 592-8 Microtubules and the plus-end-directed microtubule motor Kinesin I are required for the selective accumulation of oskar mRNA at the posterior cortex of the Drosophila melanogaster oocyte, which is essential to posterior patterning and pole plasm assembly. We present evidence that microtubule minus ends associate with the entire cortex, and that Kinesin and microtubules are not required for oskar mRNA association with the posterior pole, but prevent ectopic localization of this transcript and the pole plasm proteins Oskar and Vasa to other cortical regions. Cortical binding of oskar mRNA seems to be dependent on the actin cytoskeleton. We conclude that most of the actin-rich oocyte cortex can support pole plasm assembly, and propose that Kinesin restricts pole plasm formation to the posterior by moving oskar mRNA away from microtubule-rich lateral and anterior cortical regions. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Cha Byeong-Jik BJ Serbus Laura R LR Koppetsch Birgit S BS Theurkauf William E WE eng Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Molecular Motors 0 RNA, Messenger 0 oskar protein, Drosophila EC 3.6.1.- Kinesin IM Animal Cell Polarity Drosophila Proteins genetics Drosophila melanogaster cytology genetics metabolism Female In Situ Hybridization, Fluorescence Kinesin chemistry genetics metabolism Microtubules metabolism Models, Biological Molecular Motors chemistry genetics metabolism Mutation Oocytes metabolism ultrastructure RNA, Messenger genetics metabolism Support, Non-U.S. Gov't FBrf0059077 93241168 8479437 1993 05 26 1993 05 26 2000 12 18

0026-8925 238 1-2 1993 Apr The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. 33-7 The Drosophila Tumorous-lethal (Tum-l) mutation acts as an activated oncogene, causing hematopoietic neoplasms, overproliferation, and premature differentiation. Tum-l is a dominant mutation in the hopscotch (hop) locus, which is required for cell division and for proper embryonic segmentation. The Tum-l temperature-sensitive period for melanotic tumor formation includes most of larval and pupal development. Department of Biological Sciences, University of Southern Mississippi, Hattiesburg 39406. Hanratty W P WP Dearolf C R CR eng CA24488 CA NCI Journal Article

GERMANY Mol Gen Genet 0125036 IM Tum-1 hop Animal Crosses, Genetic Drosophila melanogaster genetics Female Genes, Dominant Genes, Lethal Genetic Complementation Test Male Mutation Oncogenes Recombination, Genetic Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Temperature Time Factors FBrf0083948 96155609 8574581 1996 03 12 1996 03 12 2003 06 16

0960-9822 5 11 1995 Nov 1 Pattern formation. Gurken meets torpedo for the first time. 1252-4 Intercellular communication between oocyte and follicle cells, mediated by the gurken-torpedo/DER signalling pathway, has a crucial role in determining both anterior-posterior and dorsal-ventral polarity in Drosophila. Department of Molecular Biology, Princeton University, New Jersey 08544, USA. Gavis E R ER eng Journal Article Review Review, Tutorial

ENGLAND Curr Biol 9107782 0 Insect Hormones 0 Receptors, Invertebrate Peptide 0 epidermal growth factor receptor homolog, Drosophila 0 gurken protein, Drosophila 76057-06-2 Transforming Growth Factors EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Cell Communication Cell Polarity Drosophila melanogaster embryology Female Insect Hormones metabolism Oocytes physiology Ovarian Follicle physiology Receptor, Epidermal Growth Factor metabolism Receptors, Invertebrate Peptide metabolism Transforming Growth Factors metabolism 14 FBrf0074608 94291191 8020091 1994 08 04 1994 08 04 2000 12 18

0092-8674 77 7 1994 Jul 1 Cell cycle progression in the developing Drosophila eye: roughex encodes a novel protein required for the establishment of G1. 1003-14 The onset of pattern formation in the developing Drosophila eye is marked by the simultaneous synchronization of all cells in the G1 phase of the cell cycle. These cells will then either commit to another round of cell division or differentiate into neurons. Although cell cycle synchronization occurs in roughex (rux) mutants, cells circumvent G1 and all cells enter S phase, including cells that would normally differentiate. This leads to defects in early steps of pattern formation and cell fate determination. rux is suppressed by mutations in genes that promote cell cycle progression (i.e., cyclin A and string) and enhanced by mutations in genes that promote differentiation (i.e., Ras1 and Star). rux encodes a novel protein of 335 amino acids. We propose that rux functions as a negative regulator of G1 progression in the developing eye. Department of Biological Chemistry, University of California, Los Angeles 90024. Thomas B J BJ Gunning D A DA Cho J J Zipursky L L eng GENBANK U19583 Journal Article

UNITED STATES Cell 0413066 0 Cyclins 0 DNA, Complementary 0 Eye Proteins 0 Insect Hormones 0 roughex protein 0 string protein, Drosophila IM cycA rux stg Amino Acid Sequence Animal Base Sequence Cell Cycle Cyclins physiology DNA, Complementary genetics Drosophila melanogaster cytology genetics Eye growth & development Eye Proteins genetics Genes, Structural, Insect Genes, Suppressor Genes, ras Insect Hormones genetics Molecular Sequence Data Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0052657 90231408 2109831 1990 05 25 1990 05 25 2000 12 18

0028-0836 344 6268 1990 Apr 19 Sex determination compared in Drosophila and Caenorhabditis. 721-8 Fruitflies and nematodes show many similarities in the general organization of the gene networks that control sexual dimorphism and dosage compensation. In contrast, the underlying molecular mechanisms appear to be very different in these two species. Developmental processes such as sex determination need not be strongly conserved in evolution. MRC Laboratory of Molecular Biology, Cambridge, UK. Hodgkin J J eng Journal Article Review Review Literature

ENGLAND Nature 0410462 IM Animal Caenorhabditis genetics Comparative Study Dosage Compensation (Genetics) Drosophila melanogaster genetics Female Genes, Regulator Germ Cells Male Phenotype Sex Determination (Analysis) Support, Non-U.S. Gov't X Chromosome 61 FBrf0128423 20307680 10849071 2000 09 01 2000 09 01 2000 12 18

0018-067X 84 ( Pt 4) 2000 Apr Sexual isolation of genetically differentiated sympatric populations of Drosophila melanogaster in Brazzaville, Congo: the first step towards speciation? 468-75 Two sympatric populations of Drosophila melanogaster were collected in the Brazzaville area in Congo, one from the suburban countryside and the other from a brewery located in the city. They were compared for several genetically determined traits including morphology, allozymes, microsatellites, cuticular hydrocarbons, and sexual behaviour. The two populations were similar to other African populations for morphological traits, but differed significantly from each other for all other characters. The countryside population resembled other African populations, whereas the urban population was consistently similar to European populations. Mating choice experiments showed incipient reproductive separation between the populations. In agreement with the hypothesis that D. melanogaster originated in Africa and spread to the rest of the world by invading human-modified habitats, we suggest that man-adapted fruit fly populations have returned 'back to Africa', and remained partially isolated from older native stocks. Laboratoire Populations, Génétique et Evolution, CNRS, 91198 Gif/Yvette Cedex, France. capy@pge.cnrs-gif.fr Capy P P Veuille M M Paillette M M Jallon J M JM Vouidibio J J David J R JR eng Journal Article

ENGLAND Heredity 0373007 IM Animal Congo Copulation Drosophila melanogaster classification genetics Ecosystem Genetics, Population Geography Sex Behavior, Animal classification Species Specificity Variation (Genetics) FBrf0058562 93170637 8382175 1993 03 23 1993 03 23 2000 12 18

0016-6731 133 2 1993 Feb Genetic instability in Drosophila melanogaster mediated by hobo transposable elements. 315-34 Eight independent recessive lethal mutations that occurred on derivatives of an unstable X chromosome (Uc) in Drosophila melanogaster were analyzed by a combination of genetic and molecular techniques. Seven of the mutations were localized to complementation groups in polytene chromosome bands 6E; 7A. In situ hybridization and genomic Southern analysis established that hobo transposable elements were associated with all seven of the mutations. Six mutations involved deletions of DNA, some of which were large enough to be seen cytologically, and in each case, a hobo element was inserted at the junction of the deletion's breakpoints. A seventh mutation was associated with a small inversion between 6F and 7A-B and a hobo element was inserted at one of its breakpoints. One of the mutant chromosomes had an active hobo-mediated instability, manifested by the recurrent production of mutations of the carmine (cm) locus in bands 6E5-6. This instability persisted for many generations in several sublines of an inbred stock. Two levels of instability, high and basal, were distinguished. Sublines with high instability had two hobo elements in the 6E-F region and produced cm mutations by deleting the segment between the two hobos; a single hobo element remained at the junction of the deletion breakpoints. Sublines with low instability had only one hobo element in the 6E-F region, but they also produced deletion mutations of cm. Both types of sublines also acquired hobo-mediated inversions on the X chromosome. Collectively, these results suggest that interactions between hobo elements are responsible for the instability of Uc. It is proposed that interactions between widely separated elements produce gross rearrangements that restructure the chromosome and that interactions between nearby elements cause regional instabilities manifested by the recurrence of specific mutations. These regional instabilities may arise when a copy of hobo transposes a short distance, creating a pair of hobos that can interact to produce small rearrangements. Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108-1095. Sheen F F Lim J K JK Simmons M J MJ eng ES01960 ES NIEHS GM31106 GM NIGMS GM40263 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements IM cm Animal Blotting, Southern Chromosome Mapping DNA Transposable Elements genetics Drosophila melanogaster genetics Genes, Lethal Genes, Recessive Genetic Complementation Test Inversion (Genetics) Sequence Deletion Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome FBrf0152005 22253746 12368260 2002 10 07 2002 11 05

0890-9369 16 19 2002 Oct 1 Fragile X-related protein and VIG associate with the RNA interference machinery. 2491-6 RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease. Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA. Caudy Amy A AA Myers Mike M Hannon Gregory J GJ Hammond Scott M SM eng R01-GM62534 GM NIGMS Journal Article

United States Genes Dev 8711660 0 AGO2 protein, Drosophila 0 Drosophila Proteins 0 FMR1 protein, Drosophila 0 Insect Proteins 0 MicroRNAs 0 RNA, Double-Stranded 0 RNA, Small Interfering 0 RNA-Binding Proteins 0 RNA-Induced Silencing Complex 0 VIG protein, Drosophila IM Amino Acid Sequence Animal Cell Line Drosophila Proteins genetics isolation & purification metabolism Drosophila melanogaster Gene Silencing Insect Proteins genetics isolation & purification metabolism MicroRNAs metabolism Molecular Sequence Data RNA, Double-Stranded metabolism RNA, Small Interfering metabolism RNA-Binding Proteins genetics isolation & purification metabolism RNA-Induced Silencing Complex isolation & purification metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0055547 92208942 1339308 1992 05 01 1992 05 01 2000 12 18

0092-8674 69 1 1992 Apr 3 chickadee encodes a profilin required for intercellular cytoplasm transport during Drosophila oogenesis. 173-84 The entire cytoplasmic contents of 15 highly polyploid nurse cells are transported rapidly to the oocyte near the end of Drosophila oogenesis. chickadee is one of a small group of genes whose mutant phenotype includes a disruption of this nurse cell cytoplasm transport. We have cloned the chickadee gene and found that cDNA clones encode a protein 40% identical to yeast and Acanthamoeba profilin. The nurse cells from chickadee egg chambers that lack ovary-specific profilin fail to synthesize cytoplasmic actin networks correctly. In addition, the nurse cell nuclei in chickadee egg chambers become displaced and often partially stretched through the channels leading into the oocyte, blocking the flow of cytoplasm. We suggest that the newly synthesized cytoplasmic actin networks are responsible for maintaining nuclear position in the nurse cells. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510. Cooley L L Verheyen E E Ayers K K eng GENBANK M84163 M84182 M84528 M84529 S72766 S72767 S72768 S72769 S72771 X63098 GM43301 GM NIGMS T32 HD07149 HD NICHD Journal Article

UNITED STATES Cell 0413066 0 Contractile Proteins 0 Microfilament Proteins 0 profilin IM chic Amino Acid Sequence Animal Base Sequence Biological Transport, Active genetics Blotting, Southern Contractile Proteins genetics Cytoplasm metabolism Drosophila melanogaster genetics Female Male Microfilament Proteins genetics Molecular Sequence Data Oogenesis genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0155680 22419253 12530954 2003 01 17 2003 03 14 2003 09 15

1534-5807 4 1 2003 Jan Epithelial polarity in flies: more than just crumbs. 1-3 The plasma membrane of polarized epithelial cells is composed of different domains, which are associated with specific protein complexes. Recent studies in Drosophila shed new light on the functional interactions of these protein complexes during epithelial differentiation in embryogenesis. Institut für Genetik, Heinrich-Heine Universität Düsseldorf, Universitätsstrasse 1, D-40225, Düsseldorf, Germany. Müller H-Arno J HA eng Journal Article

United States Dev Cell 101120028 0 Drosophila Proteins 0 Macromolecular Systems 0 Membrane Proteins 0 Scribble protein, Drosophila 0 crb protein, Drosophila IM Dev Cell. 2003 Feb;4(2):285 Animal Cell Membrane chemistry metabolism Cell Polarity Drosophila Proteins metabolism Drosophila melanogaster cytology embryology metabolism Epithelial Cells cytology metabolism Macromolecular Systems Membrane Proteins metabolism Morphogenesis FBrf0043925 86298406 3091259 1986 10 09 1986 10 09 2000 12 18

0092-8674 46 5 1986 Aug 29 Local function of the Notch gene for embryonic ectodermal pathway choice in Drosophila. 773-83 Mutations at the Notch locus affect the fate of cells in the neurogenic region of the Drosophila embryo so that epidermal precursors become neuroblasts. We have analyzed the cellular requirements for wild-type Notch gene function by means of genetic mosaics, using a cuticle marker to distinguish hypodermal cell genotype. Cells that were genotypically Notch never gave rise to hypoderm within the neurogenic region of mosaic embryos. Mosaic dividing lines within the neurogenic region juxtapose N+ hypoderm with regions of neural hypertrophy. This autonomous action of Notch in hypodermal cells is consistent with a local function of the protein during neurogenesis. Comparison of clone distribution in Notch mosaics and controls suggests that islands of wild-type hypodermal cells fail to differentiate cuticle. Hoppe P E PE Greenspan R J RJ eng GM31104 GM NIGMS T32GM07312 GM NIGMS Journal Article

UNITED STATES Cell 0413066 IM Animal Drosophila melanogaster embryology genetics Ectoderm physiology Epidermis embryology Genes Larva Mosaicism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0158840 22482237 12593977 2003 02 20 2003 04 18 2003 05 21

0959-4388 13 1 2003 Feb Genetic control of Drosophila nerve cord development. 8-15 The Drosophila ventral nerve cord has been a central model system for studying the molecular genetic mechanisms that control CNS development. Studies show that the generation of neural diversity is a multistep process initiated by the patterning and segmentation of the neuroectoderm. These events act together with the process of lateral inhibition to generate precursor cells (neuroblasts) with specific identities, distinguished by the expression of unique combinations of regulatory genes. The expression of these genes in a given neuroblast restricts the fate of its progeny, by activating specific combinations of downstream genes. These genes in turn specify the identity of any given postmitotic cell, which is evident by its cellular morphology and choice of neurotransmitter. Department of Genetics, Washington University School of Medicine, 4566 Scott Avenue, St Louis, MO 63110, USA. jskeath@genetics.wustl.edu Skeath James B JB Thor Stefan S eng Journal Article Review Review, Tutorial

England Curr Opin Neurobiol 9111376 IM S Animal Body Patterning genetics Cell Differentiation genetics Cell Lineage genetics Central Nervous System cytology embryology physiology Drosophila melanogaster cytology embryology physiology Ganglia, Invertebrate cytology embryology physiology Gene Expression Regulation, Developmental genetics Models, Animal Neurons cytology physiology Stem Cells cytology physiology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. 64 NASA Discipline Evolutionary Biology Non-NASA Center Skeath J B JB Washington U Sch Med, St Louis, MO FBrf0083130 96028301 7552175 1995 11 03 1995 11 03 2000 12 18

0960-9822 5 6 1995 Jun 1 Secretion of the amino-terminal fragment of the hedgehog protein is necessary and sufficient for hedgehog signalling in Drosophila. 643-50 BACKGROUND: The Drosophila segment polarity gene hedgehog encodes a member of a family of secreted proteins that are involved in a variety of patterning processes, in both vertebrates and invertebrates. Some of these processes depend upon short-range or contact-dependent interactions, whereas others seem to involve long-range signalling. Two different models have been proposed to account for the execution of these contrasting processes by the same proteins: one postulates that Hedgehog acts exclusively over short distances, its long-range influences being effected through regulation of other signalling factors; the second postulates that different aspects of Hedgehog activity are mediated by distinct forms of the protein that are generated by autoproteolysis. RESULTS: We have investigated these models by mutating the hedgehog coding region such that only the amino-terminal or carboxy-terminal half of the protein is secreted. Deletion of the carboxy-terminal portion has little effect on the signalling activity of the protein, whereas abolishing the secretion of the amino-terminal half leads to a complete loss of signalling. In addition, we find that increases in the level of expression within the normal hedgehog transcriptional domain of either the wild-type protein or the carboxy-terminal-deleted form expand the range of activity to a limited extent, but have only minor effects on cell identity. CONCLUSIONS: In Drosophila, all of the signalling activity of Hedgehog resides in the amino-terminal portion of the protein, the secretion of which is essential for its function. The range of Hedgehog is limited by the close association of the amino-terminal peptide with the cell surface but can be extended by elevating the level of its expression. Molecular Embryology Laboratory, Imperial Cancer Research Fund, London, UK. Fietz M J MJ Jacinto A A Taylor A M AM Alexandre C C Ingham P W PW eng Journal Article

ENGLAND Curr Biol 9107782 0 Insect Hormones 0 Peptide Fragments 0 Proteins 0 Recombinant Proteins 0 dpp protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM dpp hh Amino Acid Sequence Animal Base Sequence Drosophila melanogaster embryology genetics physiology Gene Expression Regulation Insect Hormones physiology Larva Molecular Sequence Data Morphogenesis genetics Peptide Fragments physiology Proteins chemistry physiology Recombinant Proteins metabolism Signal Transduction Support, Non-U.S. Gov't Transcription, Genetic Wing embryology growth & development FBrf0088548 96245435 8814781 1996 10 10 1996 10 10 2000 12 18

0965-1748 26 4 1996 Apr Biochemistry of insect learning: lessons from bees and flies. 327-35 Recent advances in the study of learning in insects are examined with an emphasis on two of the most powerful model systems, the honeybee (Apis mellifera) and the fruit fly (Drosophila melanogaster). The honeybee exhibits easily manipulated feeding behavior coupled with extremely high mnemonic fidelity. The size of the honeybee brain has allowed for electrophysiological analysis of the neural correlates of behavior, sometimes with single cell resolution, as well as identification of critical brain regions. Drosophila has proved to be invaluable in the genetic dissection of learning. Through analysis of learning and memory mutants the biochemistry of critical steps has been elucidated and the temporal phases of memory in the fly have been described. Two regions of brain neurophil are essential for olfactory learning in these species: the antennal lobes and the mushroom bodies. In spite of similarities, temporal, and possibly biochemical aspects of learning differ markedly between these organisms. Department of Cell Biology and Neurology, Baylor College of Medicine, Houston, TX 77030, USA. Meller V H VH Davis R L RL eng Journal Article Review Review, Tutorial

ENGLAND Insect Biochem Mol Biol 9207282 0 Neurotransmitters IM Animal Bees physiology Behavior, Animal Drosophila melanogaster physiology Learning physiology Memory physiology Neurotransmitters physiology 81 FBrf0039213 84085448 6418585 1984 02 14 1984 02 14 2000 12 18

0012-1606 100 2 1983 Dec Clonal analysis of the tissue specificity of recessive female-sterile mutations of Drosophila melanogaster using a dominant female-sterile mutation Fs(1)K1237. 365-73 Using the newly isolated, germ line-dependent dominant female-sterile mutation Fs(1)K1237, we have characterized the germ line or somatic line dependence of 25 X-linked recessive female-sterile mutations. Since Fs(1)K1237/+ females fail to lay eggs, only germ line cells which lose Fs(1)K1237 as a result of X-ray-induced mitotic recombination are capable of producing eggs. Such recombination events will render genes on the homologous chromosome homozygous. If this chromosome carries a recessive female-sterile mutation, the fertility will be restored only if the altered function is not required in the germ line. Using this test, we have classified 25 recessive female-sterile mutations: 12 affect germ line function, 12 affect somatic line function, and one gave an ambiguous result for which an explanation is proposed. For a few of the somatic line-dependent mutants, we found that some eggs derived from germ line clones showed the same phenotype as eggs laid by females homozygous for the recessive female-sterile mutation. These results are discussed in terms of a coincident production of clones in the follicle cells. Perrimon N N Gans M M eng Journal Article

UNITED STATES Dev Biol 0372762 IM Animal Chromosome Mapping Clone Cells cytology Drosophila melanogaster cytology genetics Female Genes, Recessive Genitalia embryology Infertility, Female genetics pathology Linkage (Genetics) Mutation Oogenesis Support, Non-U.S. Gov't X Chromosome FBrf0037601 83103095 6817923 1983 03 24 1983 03 24 2000 12 18

0092-8674 29 3 1982 Jul Cuticle protein genes of Drosophila: structure, organization and evolution of four clustered genes. 1027-40 Most of a 9 kb region of the Drosophila genome containing genes for several cuticle proteins has been sequenced. Five cuticle-gene-like sequences have been identified and mapped. Amino acid sequences of four of the five major third instar cuticle proteins have been determined. These four sequences are identical with those predicted from the sequences of four of the five genes. Two cuticle genes are transcribed in one direction and two in the opposite direction. The fifth cuticle-like gene is judged to be a pseudogene because several features of its structure and the absence of detectable transcripts suggest it is nonfunctional. Sequence comparisons indicate that it arose by an unequal crossing-over event involving two closely related and adjacent cuticle genes. Each of the four cuticle genes contains a signal peptide coding sequence interrupted by a short intervening sequence (about 60 bp) at a conserved site. Conserved sequences occur in the 5' mRNA untranslated region, in the adjacent 35 bp of upstream flanking sequence and at -200 bp from the mRNA start position in each of the cuticle genes. We discuss the structure, organization and evolution of these cuticle genes as a model small gene family. Snyder M M Hunkapiller M M Yuen D D Silvert D D Fristrom J J Davidson N N eng GENBANK J01080 J01081 Journal Article

UNITED STATES Cell 0413066 0 Proteins IM Amino Acid Sequence Animal Base Sequence Drosophila melanogaster genetics Evolution Gene Expression Regulation Genes, Structural Linkage (Genetics) Proteins genetics Translation, Genetic FBrf0056208 93012920 1398052 1992 11 03 1992 11 03 2000 12 18

0016-6731 132 1 1992 Sep Differentiation of a male-specific muscle in Drosophila melanogaster does not require the sex-determining genes doublesex or intersex. 179-91 A pair of muscles span the fifth abdominal segment of male but not female Drosophila melanogaster adults. To establish whether genes involved in the development of other sexually dimorphic tissues controlled the differentiation of sex-specific muscles, flies mutant for five known sex-determining genes were examined for the occurrence of male-specific abdominal muscles. Female flies mutant for alleles of Sex-lethal, defective in sex determination, or null alleles of transformer or transformer-2 are converted into phenotypic males that formed male-specific abdominal muscles. Both male and female flies, when mutant for null alleles of doublesex, develop as nearly identical intersexes in other somatic characteristics. Male doublesex flies produced the male-specific muscles, whereas female doublesex flies lacked them. Female flies, even when they inappropriately expressed the male-specific form of doublesex mRNA, failed to produce the male-specific muscles. Therefore, the wild-type products of the genes Sex-lethal, transformer and transformer-2 act to prevent the differentiation of male-specific muscles in female flies. However, there is no role for the genes doublesex or intersex in either the generation of the male-specific muscles in males or their suppression in females. Zoology Department, University of Washington, Seattle 98195. Taylor B J BJ eng 1F32NS08618 NS NINDS Journal Article

UNITED STATES Genetics 0374636 IM Sxl ix sxl tra tra-2 Animal Drosophila melanogaster genetics Female Male Muscles cytology Mutation Phenotype Sex Characteristics Sex Differentiation genetics Support, U.S. Gov't, P.H.S. FBrf0098304 97459689 9315649 1997 10 23 1997 10 23 2001 11 28

0270-7306 17 10 1997 Oct Drosophila melanogaster deficient in protein kinase A manifests behavior-specific arrhythmia but normal clock function. 5915-22 Drosophila melanogaster bearing mutations in the DCO gene, which encodes the major catalytic subunit of cAMP-dependent protein kinase (PKA), displays arrhythmic locomotor activity strongly suggesting a role for PKA in the circadian timing system. This arrhythmicity might result from a requirement for PKA activity in photic resetting pathways, the timekeeping mechanism itself, or downstream effector pathways controlling overt behavioral rhythms. To address these possibilities, we examined the protein and mRNA products from the clock gene period (per) in PKA-deficient flies. The per protein (PER) and mRNA products undergo daily cycles in the heads and bodies of DCO mutants that are indistinguishable from those observed in control wild-type flies. These results indicate that PKA deficiencies affect the proper functioning of elements downstream of the Drosophila timekeeping mechanism. The requirement for PKA in the manifestation of rhythmic activity was preferentially greater in the absence of environmental cycles. However, PKA does not appear to play a universal role in output functions because the clock-controlled eclosion rhythm is normal in DCO mutants. Our results suggest that PKA plays a critical role in the flow of temporal information from circadian pacemaker cells to selective behaviors. Biochemistry Graduate Program, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA. Majercak J J Kalderon D D Edery I I eng NS34958 NS NINDS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Nuclear Proteins 0 PER protein, Drosophila 0 RNA, Messenger EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Behavior, Animal physiology Biological Clocks genetics Circadian Rhythm genetics Cyclic AMP-Dependent Protein Kinases physiology Drosophila melanogaster enzymology genetics physiology Homozygote Larva Male Motor Activity genetics Mutation Nuclear Proteins genetics RNA, Messenger metabolism Support, U.S. Gov't, P.H.S. FBrf0086502 96197128 8626022 1996 06 25 1996 06 25 2000 12 18

0012-1606 174 1 1996 Feb 25 inscuteable, a neural precursor gene of Drosophila, encodes a candidate for a cytoskeleton adaptor protein. 65-81 In Drosophila, neural precursor genes are expressed in neural progenitor cells as the neuroblasts and sense organ mother cells. These genes are thought to control the fate and/or behavior of neural progenitor cells once their fate decision has been made. We have isolated and characterized a novel neural precursor gene, inscuteable, whose expression is coincident with sites of cell shape changes or cell and tissue movement in the embryo, e.g., neuroblasts, trachea, Malphigian tubules, and in pupal wing epithelia. The Inscuteable protein is localized to the apical submembranous surface of neuroblasts and other cell types and shows certain features common to a family of putative cytoskeletal associated proteins. The inscuteable mutant phenotype, together with these other observations, suggests a possible role for the protein in cytoskeleton organization. Institut für Entwicklungsbiologie, Universität zu Köln, Cologne, Germany. Kraut R R Campos-Ortega J A JA eng GENBANK X83111 Journal Article

UNITED STATES Dev Biol 0372762 0 Cytoskeletal Proteins 0 Nerve Tissue Proteins 0 RNA, Messenger 0 inscuteable protein IM Amino Acid Sequence Animal Ankyrin Repeat Cell Adhesion Chromosome Mapping Cytoskeletal Proteins chemistry genetics Drosophila melanogaster genetics Gene Expression Regulation, Developmental Genes, Structural, Insect Molecular Sequence Data Nerve Tissue Proteins chemistry genetics Neurons cytology RNA, Messenger genetics Support, Non-U.S. Gov't Transcription, Genetic FBrf0082675 95348061 7622453 1995 08 25 1995 08 25 2000 12 18

0021-9258 270 28 1995 Jul 14 Characterization of a Stat-like DNA binding activity in Drosophila melanogaster. 16510-3 The cytokine signaling pathways that activate the Janus family of tyrosine kinases (Jaks) and the "signal transducers and activators of transcription" (Stats) have been well characterized in mammalian systems. Work shown here provides evidence that an analogous signaling pathway exists in Drosophila melanogaster. Because many of the ligand-receptor pairs in Drosophila have not been fully characterized, it was necessary to bypass the receptor stimulation event that normally triggers intracellular Jak/Stat activation. This was done by treating Drosophila Schneider 2 cells with vanadate/peroxide, which has been shown to closely mimic some signaling events triggered by interferon gamma, including the activation of Jak1, Jak2, and the Stat1 alpha protein. Evidence presented here demonstrates that vanadate/peroxide can induce a gamma response region binding complex in Drosophila Schneider 2 cells. This complex contains two phosphoproteins of 100 and 150 kDa, respectively, and shares many features with the vanadate/peroxide-stimulated binding complex in the mammalian system. Southern blot analysis of genomic DNA using the src homology domain 2 (SH2) of Stat1 alpha confirms the presence of a related gene in the Drosophila genome. Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland 20892, USA. Sweitzer S M SM Calvo S S Kraus M H MH Finbloom D S DS Larner A C AC eng Journal Article

UNITED STATES J Biol Chem 2985121R 0 DNA-Binding Proteins 0 Trans-Activators 0 Vanadates 55520-40-6 Tyrosine IM Animal Base Sequence Blotting, Southern DNA-Binding Proteins analysis Drosophila melanogaster chemistry genetics Human Molecular Sequence Data Phosphorylation Promoter Regions (Genetics) Support, Non-U.S. Gov't Trans-Activators analysis Tyrosine metabolism Vanadates pharmacology FBrf0055783 92297166 1605861 1992 07 21 1992 07 21 2002 11 01

1044-5498 11 5 1992 Jun Molecular analysis of a cytochrome P450 gene of family 4 on the Drosophila X chromosome. 397-404 A member of the cytochrome P450 superfamily has been identified within region 2D of the Drosophila X chromosome. The sequence of this gene shows strongest homology with P450 family 4 genes, and has thus been named CYP4D1 in accordance with convention. This P450 gene is expressed throughout Drosophila development, with the highest levels of transcript accumulation occurring during late larval stages. A fragment of Drosophila genomic DNA including the CYP4D1 gene has been reintroduced into the germ line by P-element-mediated transformation. This transduced fragment does not rescue any of the lethal mutations that have been identified in this genetically well-characterized region of the Drosophila genome. Section of Genetics and Development, Cornell University, Ithaca, NY 14853-2703. Gandhi R R Varak E E Goldberg M L ML eng GENBANK L08493 L08494 L08495 L08496 L08497 S38220 S38221 S72771 X65482 X67645 Journal Article

UNITED STATES DNA Cell Biol 9004522 0 RNA, Messenger 9035-51-2 Cytochrome P-450 Enzyme System IM CYP4D1 Amino Acid Sequence Animal Base Sequence Chromosome Mapping Comparative Study Cytochrome P-450 Enzyme System genetics Drosophila melanogaster genetics Gene Expression Genes, Structural Genetic Complementation Test Molecular Sequence Data Multigene Family RNA, Messenger genetics Restriction Mapping Sequence Alignment FBrf0128654 20313087 10854336 2000 07 17 2000 07 17 2003 02 03

1465-7392 2 6 2000 Jun Drosophila p53: meeting the Grim Reaper. E100-2 The recent discovery of a Drosophila orthologue of the p53 tumour suppressor promises new insights into the complex function, regulation and evolution of one of the most intensely studied human disease proteins. Steller H H eng News

ENGLAND Nat Cell Biol 100890575 0 Insect Proteins 0 Neuropeptides 0 Peptides 0 Protein p53 0 grim protein, Drosophila 0 reaper peptide, Drosophila IM Animal Apoptosis radiation effects Cell Cycle radiation effects Drosophila melanogaster cytology genetics radiation effects Human Insect Proteins genetics metabolism Neuropeptides genetics metabolism Peptides genetics metabolism Protein p53 genetics metabolism FBrf0044150 87031226 3095163 1986 12 11 1986 12 11 2000 12 18

0012-1606 118 1 1986 Nov l(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila. 28-41 The maternal and zygotic effect phenotypes of mutations at the l(1)hopscotch (l(1)hop) locus are described. l(1)hop is located in 10B6-8 on the salivary gland chromosome map and 17 alleles have been characterized. A complex complementation pattern is observed among the 17 alleles. The lethal phase of null alleles of l(1)hop occurs at the larval-pupal interface associated with a small disc phenotype. Embryos produced from homozygous l(1)hop germline clones show segment specific defects. The extent of these defects depends upon both the strength of the allele and the paternal contribution. In the most extreme case embryos exhibit defects associated with five segments T2, T3, A4, A5, and A8. In the less extreme phenotype defects are only associated with A5. Thus, activity of l(1)hop+ is required both for the maintenance and continued cell division of diploid imaginal precursors and for the establishment of the full array of segments. Perrimon N N Mahowald A P AP eng HD-17608 HD NICHD Journal Article

UNITED STATES Dev Biol 0372762 IM Abdomen growth & development Animal Chromosome Mapping Dosage Compensation (Genetics) Drosophila melanogaster embryology genetics growth & development Genes, Lethal Genetic Complementation Test Infertility genetics Larva Morphogenesis Mutation Phenotype Pupa Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Thorax growth & development FBrf0111986 20014925 10545463 1999 12 17 1999 12 17 2001 11 02

0016-6731 153 3 1999 Nov The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions. 1333-56 In the studies reported here, we have examined the properties of the Mcp element from the Drosophila melanogaster bithorax complex (BX-C). We have found that sequences from the Mcp region of BX-C have properties characteristic of Polycomb response elements (PREs), and that they silence adjacent reporters by a mechanism that requires trans-interactions between two copies of the transgene. However, Mcp trans-regulatory interactions have several novel features. In contrast to classical transvection, homolog pairing does not seem to be required. Thus, trans-regulatory interactions can be observed not only between Mcp transgenes inserted at the same site, but also between Mcp transgenes inserted at distant sites on the same chromosomal arm, or even on different arms. Trans-regulation can even be observed between transgenes inserted on different chromosomes. A small 800-bp Mcp sequence is sufficient to mediate these long-distance trans-regulatory interactions. This small fragment has little silencing activity on its own and must be combined with other Polycomb-Group-responsive elements to function as a "pairing-sensitive" silencer. Finally, this pairing element can also mediate long-distance interactions between enhancers and promoters, activating mini-white expression. Department of Molecular Biology, Princeton University, Princeton, New Jersey 08540, USA. Muller M M Hagstrom K K Gyurkovics H H Pirrotta V V Schedl P P eng Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 fushi tarazu protein 0 ultrabithorax protein 134549-01-2 Polycomb protein, insect IM Animal Animals, Genetically Modified DNA-Binding Proteins genetics Drosophila melanogaster genetics Gene Expression Regulation Homeodomain Proteins genetics Insect Proteins genetics Models, Genetic Regulatory Sequences, Nucleic Acid Restriction Mapping Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0134684 21109805 11167131 2001 02 22 2001 06 14

1357-2725 33 1 2001 Jan Transcription of Dfos is stimulated by brain tumours of l(2)gl-deficient larvae of Drosophila melanogaster. 45-51 Mutations in the tumour suppressor gene l(2)gl cause formation of brain and imaginal disc tumours. The product of this gene was suggested to be a part of an intercellular communication system, regulating cell growth and differentiation. Oncogenic activation of many signalling pathways, involved in similar processes, result in increased activity of the AP-1 family of transcription factors. In this paper we explored the interaction between the cancer mutation l(2)gl and the level of transcription of the AP-1 proteins. We report that in brain tumours from l(2)gl-deficient larvae, transcription of the Drosophila melanogaster c-fos homologue was stimulated but that of the c-jun homologue was unchanged. Our results provide further evidence that the protein l(2)gl is a component of a signalling pathway, a nuclear target of which is the AP-1 family of transcription factors. Department of Genetics, Faculty of Biology, University of Sofia, 8 Dragan Tsankov Str., 1421 Sofia, Bulgaria. Nedelcheva M M Topouzova T T Genova G G eng Journal Article

England Int J Biochem Cell Biol 9508482 0 Plasmids 0 Proto-Oncogene Proteins c-jun 0 Transcription Factor AP-1 IM Animal Brain metabolism Brain Neoplasms genetics Cell Nucleus metabolism Drosophila melanogaster embryology genetics Genes, fos genetics In Situ Hybridization In Situ Hybridization, Fluorescence Mutation Plasmids metabolism Proto-Oncogene Proteins c-jun metabolism Signal Transduction Transcription Factor AP-1 metabolism Transcription, Genetic FBrf0057556 92390350 1518806 1992 10 07 1992 10 07 2000 12 18

0027-8424 89 17 1992 Sep 1 In vivo self-association of the Drosophila rel-protein dorsal. 7861-5 The Drosophila morphogen dorsal, KBF1, NF-kappa B, and the proto-oncogene c-rel belong to the rel family of transcription factors whose function is regulated post-translationally by selective nuclear import. In the early Drosophila embryo, dorsal protein is proposed to be retained in the cytoplasm through its interaction with cactus protein. The maternal dorsal group genes constitute a signal transduction pathway, which results in targeting cytoplasmic dorsal protein into the nuclei of the syncytial blastoderm embryo, in a ventral-to-dorsal gradient. The asymmetric transcriptional regulation of zygotic genes along the dorsoventral axis by the dorsal morphogen gradient establishes embryonic dorsoventral polarity. In the lymphocytes, the functional equivalent of cactus is I kappa B, which appears to retain NF-kappa B in the cytoplasm. This retention is relieved by extracellular signals in tissue culture. NF-kappa B and rel proteins each are known to function as oligomeric complexes. Here we present genetic and biochemical evidence for the existence and functional importance of an oligomeric dorsal complex in vivo. Department of Molecular Biology, Princeton University, NJ 08544. Govind S S Whalen A M AM Steward R R eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA-Binding Proteins 0 Macromolecular Systems 0 Nuclear Proteins 0 Recombinant Fusion Proteins 0 Transcription Factors 0 dorsal protein, Drosophila IM dl Animal DNA-Binding Proteins chemistry Drosophila melanogaster chemistry Macromolecular Systems Nuclear Proteins chemistry Recombinant Fusion Proteins genetics metabolism Structure-Activity Relationship Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors chemistry FBrf0073904 94257532 8199052 1994 07 05 1994 07 05 2001 11 02

0925-4773 45 2 1994 Feb Production of dominant female sterility in Drosophila melanogaster by insertion of the ovoD1 allele on autosomes: use of transformed strains to generate germline mosaics. 155-62 We have cloned a 7 kb genomic fragment containing the dominant female-sterile mutation ovoD1. This fragment confers to transgenic females a sterility phenotype, the severity of which depends both on the genetic background and the ratio of ovoD1 product to ovo+ product. Females containing two copies of the ovoD1 transgene, or those containing one recessive null allele at the ovo locus, are about as sterile as ovoD1 females. Twenty transformed strains were obtained and five of them were tested and shown to be excellent tools for identifying a germline clone of cells sustaining mitotic recombination on the autosomes. One of the tested strains carries an insert on chromosome 4, which enabled us to show that mitotic recombination on that chromosome is not a rare event: it is in fact frequent enough for the maternal effects of the zygotic lethal mutations cubitus interruptus Dominant (ciD) and l(4)29 to be studied. Centre de Génétique Moléculaire du C.N.R.S., Gif sur Yvette, France. Mével-Ninio M M Guénal I I Limbourg-Bouchon B B eng Journal Article

IRELAND Mech Dev 9101218 IM ci<up>D</up> l(4)29 ovo<up>D1</up> Alleles Animal Animals, Genetically Modified Chromosomes Drosophila melanogaster genetics Female Genes, Dominant Infertility, Female genetics Mosaicism genetics Phenotype Recombination, Genetic Support, Non-U.S. Gov't Transformation, Genetic FBrf0089583 96365467 8769644 1996 10 03 1996 10 03 2002 11 08

0890-9369 10 16 1996 Aug 15 Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. 2003-13 Members of the Hedgehog (Hh) family of secreted proteins have been identified recently as key signaling molecules that regulate a variety of inductive interactions central to the development of both Drosophila and vertebrates. Despite their widespread importance, the way in which Hh signals are transduced inside the cell remains poorly understood. The best candidate for a transcription factor that mediates Hh signaling in Drosophila is the product of the cubitus interruptus (ci) gene, a zinc finger protein that exhibits significant homology to protein products of the vertebrate GLI gene family. Here, we show that elevated levels of Ci are sufficient to activate patched (ptc) and other hh target genes, even in the absence of hh activity. We also show that Ci can function as a transcriptional activator in yeast and demonstrate that the zinc finger domain of the protein is sufficient for its target specificity. Finally, we identify sequences in the promoter region of the ptc gene, a primary target of Hh signaling, that are identical to the consensus-binding sequence of the GLI protein and are required for reporter gene expression in response to Hh activity. Taken together, our results strongly support the role for Ci as the transcriptional activator that mediates hh signaling. Molecular Embryology Laboratory, Imperial Cancer Research Fund, London, United Kingdom. Alexandre C C Jacinto A A Ingham P W PW eng Journal Article

UNITED STATES Genes Dev 8711660 0 DNA-Binding Proteins 0 Insect Hormones 0 Membrane Proteins 0 Proteins 0 RNA, Messenger 0 Repressor Proteins 0 cubitus interruptus protein 0 patched protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Base Sequence DNA-Binding Proteins physiology Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Structural, Insect Insect Hormones genetics Membrane Proteins genetics Molecular Sequence Data Promoter Regions (Genetics) Proteins genetics RNA, Messenger genetics Repressor Proteins physiology Signal Transduction Support, Non-U.S. Gov't Trans-Activation (Genetics) Transcription, Genetic Zinc Fingers FBrf0058508 93273227 8099053 1993 06 29 1993 06 29 2000 12 18

0378-1119 127 2 1993 May 30 A novel homeobox nkch4 gene from the Drosophila 93E region. 165-71 We have cloned a Drosophilia melanogaster homeobox gene that maps to bands 93D9-E2 on the right arm of the third chromosome, in the proximal region of the NK-homeobox gene cluster. Like NK-1 and nine other known homeobox genes, nkch4 (NK-cluster homeobox 4) contains an intron between the homeodomain codons for Glu44 and Val45. The nkch4 homeodomain sequence is most related to that of the human HOX11 (tcl3) T-cell oncogene (57% homology), but differs from all other homeobox genes at several conserved residues in the third helix of the homeodomain, known to be important for DNA recognition. Low levels of nkch4 transcripts were detected during late stages of embryogenesis as well as in third instar larvae and pupae. In late embryos nkch4 is expressed in the developing CNS. Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France. Jagla K K Georgel P P Bellard F F Dretzen G G Bellard M M eng GENBANK Z11704 Journal Article

NETHERLANDS Gene 7706761 0 Oligodeoxyribonucleotides IM nkch4 rp49 Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Molecular Comparative Study Drosophila melanogaster genetics Embryo, Nonmammalian physiology Gene Library Genes, Homeobox Introns Larva Molecular Sequence Data Multigene Family Oligodeoxyribonucleotides Polymerase Chain Reaction Pupa Restriction Mapping Sequence Homology, Amino Acid Support, Non-U.S. Gov't Transcription, Genetic FBrf0098343 97420753 9275195 1997 10 01 1997 10 01 2000 12 18

0027-8424 94 18 1997 Sep 2 A screen for fast evolving genes from Drosophila. 9746-50 In an attempt to quantify the rates of protein sequence divergence in Drosophila, we have devised a screen to differentiate between slow and fast evolving genes. We find that over one-third of randomly drawn cDNAs from a Drosophila melanogaster library do not cross-hybridize with Drosophila virilis DNA, indicating that they evolve with a very high rate. To determine the evolutionary characteristics of such protein sequences, we sequenced their homologs from a more closely related species (Drosophila yakuba). The amino acid substitution rates among these cDNAs are among the fastest known and several are only about 2-fold lower than the corresponding values for silent substitutions. An analysis of within-species polymorphisms for one of these sequences reveals an exceptionally high number of polymorphic amino acid positions, indicating that the protein is not under strong negative selection. We conclude that the Drosophila genome harbors a substantial proportion of genes with a very high divergence rate. Zoologisches Institut der Universität München, Luisenstrasse 14, 80333 Munich, Germany. Schmid K J KJ Tautz D D eng GENBANK AF005843 AF005844 AF005845 AF005846 AF005847 AF005848 AF005849 AF005850 AF005851 AF005852 AF005853 AF005854 AF005855 AF005856 AF005857 AF005858 AF005859 AF005860 AF005861 AF005862 AF005863 AF005864 Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 IM Animal Base Sequence Drosophila genetics Evolution, Molecular Genes, Insect Molecular Sequence Data Sequence Analysis, DNA Support, Non-U.S. Gov't FBrf0112091 20042304 10572059 2000 01 21 2000 01 21 2002 04 19

0950-1991 126 24 1999 Dec mirror controls planar polarity and equator formation through repression of fringe expression and through control of cell affinities. 5857-66 The Drosophila eye is divided into dorsal and ventral mirror image fields that are separated by a sharp boundary known as the equator. We have previously demonstrated that Mirror, a homeodomain-containing putative transcription factor with a dorsal-specific expression pattern in the eye, induces the formation of the equator at the boundary between mirror-expressing and non-expressing cells. Here, we provide evidence that suggests mirror regulates equator formation by two mechanisms. First, mirror defines the location of the equator by creating a boundary of fringe expression at the mid-point of the eye. We show that mirror creates this boundary by repressing fringe expression in the dorsal half of the eye. Significantly, a boundary of mirror expression cannot induce the formation of an equator unless a boundary of fringe expression is formed simultaneously. Second, mirror acts to sharpen the equator by reducing the mixing of dorsal and ventral cells at the equator. In support of this model, we show that clones of cells lacking mirror function tend not to mix with surrounding mirror-expressing cells. The tendency of mirror-expressing and non-expressing cells to avoid mixing with each other is not determined by their differences in fringe expression. Thus mirror acts to regulate equator formation by both physically separating the dorsal cells from ventral cells, and restricting the formation of a fng expression boundary to the border where the dorsal and ventral cells meet. Department of Biological Sciences, Stanford University, Stanford, CA, USA. Yang C H CH Simon M A MA McNeill H H eng 2R01EY09845 EY NEI Journal Article

ENGLAND Development 8701744 0 Eye Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 mirror protein, Drosophila EC 2.4.- fringe protein IM Animal Body Patterning Cell Adhesion Cell Polarity Drosophila melanogaster embryology genetics Eye Proteins genetics physiology Gene Expression Regulation, Developmental Homeodomain Proteins genetics physiology Insect Proteins biosynthesis genetics Photoreceptors, Invertebrate embryology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0055054 91149910 1900130 1991 04 02 1991 04 02 2001 11 02

0036-8075 251 4997 1991 Mar 1 Molecular nature of the Drosophila sex determination signal and its link to neurogenesis. 1071-4 In 1921 it was discovered that the sexual fate of Drosophila is determined by the ratio of X chromosomes to sets of autosomes. Only recently has it been found that the X chromosome to autosome (X:A) ratio is communicated in part by the dose of sisterless-b (sis-b), an X-linked genetic element located within the achaete-scute complex of genes involved in neurogenesis. In this report, the molecular nature of the primary sex determination signal and its relation to these proneural genes was determined by analysis of sis-b+ germline transformants. The sis-b+ function is confered by protein T4, a member of the helix-loop-helix family of transcription factors. Although T4 is shared by sis-b and scute-alpha, the regulatory regions of sis-b, which control T4 expression in sex determination, are both separable from and simpler than those of scute-alpha, which control T4 expression in neurogenesis. Dose-sensitive cooperative interactions in the assembly or binding of sis-dependent transcription factors may directly determine the activity of the female-specific promoter of Sex-lethal, the master regulator of sexual development. In this model there is no need to invoke the existence of analogous autosomal negative regulators of Sex-lethal. Department of Molecular and Cell Biology, University of California, Berkeley 94720. Erickson J W JW Cline T W TW eng GM 23468 GM NIGMS Journal Article

UNITED STATES Science 0404511 IM Sxl sis-a sis-b Animal Animals, Genetically Modified DNA Mutational Analysis Dosage Compensation (Genetics) Drosophila melanogaster genetics Female Genes, Lethal Genes, Structural Male Nervous System Physiology Restriction Mapping Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic X Chromosome physiology FBrf0042914 86059507 3934169 1986 01 22 1986 01 22 2000 12 18

0021-9258 260 30 1985 Dec 25 Acquisition of insulin-dependent protein tyrosine kinase activity during Drosophila embryogenesis. 16072-5 We have previously reported (Petruzzelli, L., Herrera, R., Garcia, R., and Rosen, O. M. (1985) Cancer Cells 3, 115-121) that adult Drosophila melanogaster contain a specific, high-affinity insulin-binding protein. Insulin-dependent protein tyrosine kinase activity has now been identified in Drosophila. Activity first appears at 6-12 h of embryogenesis, increases during the 12-18-h period and falls to low levels in the adult. 125I-insulin was cross-linked specifically and with high affinity to a protein (Mr = 135,000) throughout embryogenesis and in the adult. However, during the 6-12- and 12-18-h periods of embryogenesis when insulin-dependent protein tyrosine kinase activity is expressed, another protein (Mr = 100,000) becomes cross-linked to 125I-insulin. Crosslinking to both proteins was competitively inhibited by the addition of 100 nM insulin. We conclude that the insulin-binding and insulin-dependent protein tyrosine kinase activities of the mammalian insulin receptor are conserved in Drosophila. However, the insulin-dependent protein tyrosine kinase activity of the receptor is detected only during specific times in embryogenesis. Petruzzelli L L Herrera R R Garcia-Arenas R R Rosen O M OM eng 5R01 GM 34555 GM NIGMS 5T32 GM 07288 GM NIGMS 7R01 AM 35158 AM NIADDK Journal Article

UNITED STATES J Biol Chem 2985121R 0 Amino Acids 0 Histones 0 Phosphoproteins 0 insulin, iodo- 11061-68-0 Insulin EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Insulin IM Amino Acids analysis Animal Drosophila melanogaster embryology enzymology Embryo, Nonmammalian enzymology physiology Histones isolation & purification Insulin analogs & derivatives metabolism pharmacology Kinetics Molecular Weight Phosphoproteins isolation & purification Protein-Tyrosine Kinase isolation & purification metabolism Receptor, Insulin isolation & purification metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0049495 90060504 2511049 1990 01 10 1990 01 10 2000 12 18

0012-1606 136 2 1989 Dec Monoclonal antibody probes discriminate early and late mutant defects in development of the Drosophila retina. 411-29 Many mutations in Drosophila melanogaster affect the morphology of the adult compound eye. However, the times at which the phenotypes first become manifest in development are, in most cases, unknown; they can occur at any of a series of stages. Among mutants in which eyes appear externally similar, the developmental stage of onset of each defect may be quite different. Pattern formation in the compound eye begins during the late third larval instar in the eye imaginal disc, when a wave of morphogenesis crosses the disc from posterior to anterior. As this wave crosses the disc, there appears in its wake an array of photoreceptor neuron clusters and accessory cells that will comprise the adult ommatidia. Eye discs from 20 abnormal-eye mutants were analyzed using monoclonal antibodies that highlight various aspects of the developing array, to observe the stage at which each anomaly becomes evident. Some mutations apparently affect precursor cells, others the setting up of the pattern, others maintenance of the pattern, and still others later morphogenetic events. Division of Biology, California Institute of Technology, Pasadena 91125. Renfranz P J PJ Benzer S S eng 1 T32GM07616 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 0 Antibodies, Monoclonal IM Animal Antibodies, Monoclonal immunology Cell Differentiation Drosophila melanogaster genetics growth & development Eye growth & development Immunologic Techniques Larva Mutation Phenotype Photoreceptors cytology Pigment Epithelium of Eye growth & development Retina growth & development immunology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0088362 96281662 8681799 1996 08 22 1996 08 22 2003 06 16

0950-1991 122 7 1996 Jul E(z): a polycomb group gene or a trithorax group gene? 2189-97 The products of the Polycomb group of genes are cooperatively involved in repressing expression of homeotic selector genes outside of their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of Polycomb group genes results in the ectopic expression of both Antennapedia Complex and Bithorax Complex genes. The products of the trithorax group of genes are cooperatively involved in maintaining active expression of homeotic selector genes within their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of trithorax group genes results in reduced expression of both Antennapedia Complex and Bithorax Complex genes. Although Enhancer of zeste has been classified as a member of the Polycomb group, in this paper we show that Enhancer of zeste can also be classified as a member of the trithorax group. The requirement for Enhancer of zeste activity as either a trithorax group or Polycomb group gene depends on the homeotic selector gene locus as well as on spatial and temporal cues. Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA. LaJeunesse D D Shearn A A eng GM53058 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Hormones 0 Nucleoproteins 0 Sex combs reduced protein, Drosophila 0 trithorax gene product 0 zeste protein 146888-72-4 polyhomeotic protein, Drosophila EC 3.2.1.23 beta-Galactosidase IM Alleles Animal Central Nervous System embryology DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian chemistry Female Gene Expression Regulation, Developmental genetics Genes, Homeobox Genes, Insect Genes, Regulator Immunohistochemistry Insect Hormones genetics Male Nucleoproteins genetics Phenotype Support, U.S. Gov't, P.H.S. Temperature Transcription, Genetic Wing embryology beta-Galactosidase analysis FBrf0084048 96109607 8647397 1996 07 23 1996 07 23 2003 06 16

0016-6731 141 2 1995 Oct Molecular analysis of scabrous mutant alleles from Drosophila melanogaster indicates a secreted protein with two functional domains. 607-17 Mutations at the scabrous locus (sca) affect cell-cell signaling during neural development. Twenty-one mutant alleles of scabrous have been analyzed. Many synthesize no sca protein. In others, a defective protein is arrested intracellularly. Two mutants in which protein is not arrested must affect sca protein function outside the cell. Both affect the fibrinogen related domain (FReD), a 200-amino acid segment conserved in fibrinogen, tenascins, and other proteins. In fibrinogen, this region is involved in protein interactions and is altered in human mutations affecting blood clotting. In sca(UM2), an invariant Asp residue is replaced by Asn. In sca(MSKF) allele has dominant negative properties, indicating that the truncated amino-terminal portion interferes with the function of so me other gene product. These mutations show that the conserved FReD is essential for wild-type sca function, but suggest that the amino-terminal domain also interacts with other proteins, but other neural mutations were without effect. Models for the role of a two-domain protein in neural development are discussed. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. Hu X X Lee E C EC Baker N E NE eng GM-47892 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 Proteins 0 Recombinant Proteins 133925-66-3 scabrous protein, Drosophila 62-50-0 Ethyl Methanesulfonate IM Alleles Amino Acid Sequence Animal Base Sequence Cloning, Molecular Comparative Study DNA Transposable Elements Drosophila melanogaster genetics Ethyl Methanesulfonate pharmacology Gene Expression Genes, Insect drug effects genetics Genotype Immunohistochemistry Molecular Sequence Data Mutagenesis Mutagenesis, Insertional Proteins biosynthesis genetics Recombinant Proteins biosynthesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X-Rays FBrf0030136 77186254 405273 1977 07 29 1977 07 29 2000 12 18

0016-6731 85 2 1977 Feb Developmental genetics of the Drosophila egg. I. Identification of 59 sex-linked cistrons with maternal effects on embryonic development. 259-72 Sex-linked mutations to recessive female sterility were induced, sorted for egg-laying, mapped within broad regions and grouped by complementation tests into cistrons. The mutations have also been partially characterized for their temperature sensitivity and pleiotropic effects. Altogether 59 cistrons have been identified, including five ellelic with previously known loci: cin, fs(1)N, mk, sn, and r. All of the genes make maternal contributions to developing embryos. In some instances mutant defects are recognized in the egg envelopes; in the remainder the defects are presumably in the egg cytoplasm. For mutations in twenty-two genes, including cin, mk, and r alleles, the lethality of the maternal effect is reversed and the embryo is "rescued" by the action of a wild-type, paternal allele. The mutant strains are potentially important material for the study of developing egg envelopes and for furthering the analysis of causation in embryogenesis and its origins in oogenesis. Mohler J D JD eng Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Chromosome Mapping Drosophila melanogaster embryology Extrachromosomal Inheritance Female Genes, Lethal Genetic Code Genetic Complementation Test Infertility, Female genetics Linkage (Genetics) Mutation Oogenesis Operon Ovum ultrastructure Sex Chromosomes FBrf0049331 89168437 2493993 1989 05 09 1989 05 09 2000 12 18

0092-8674 56 6 1989 Mar 24 The maternal ventralizing locus torpedo is allelic to faint little ball, an embryonic lethal, and encodes the Drosophila EGF receptor homolog. 1085-92 The torpedo gene of Drosophila melanogaster is involved in the establishment of the dorsoventral pattern of eggshell and embryo. We have isolated new alleles of torpedo and have found that torpedo is allelic to the zygotic embryonic lethal faint little ball. We have shown that torpedo resides in subdivision 57F on the second chromosome--at the same location as the Drosophila homolog of the EGF receptor (DER). Using a cosmid that contains most of the DER coding region as a hybridization probe, we have shown that a cytologically small deficiency that eliminates torpedo activity also removes the DER gene, and that an inversion that was isolated as a strong torpedo allele breaks the coding region of the DER gene. We conclude that torpedo is the DER gene. Biology Department, Princeton University, New Jersey 08544-1003. Price J V JV Clifford R J RJ Schüpbach T T eng GM40558-01 GM NIGMS Journal Article

UNITED STATES Cell 0413066 0 epidermal growth factor receptor homolog, Drosophila 9007-49-2 DNA EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Alleles Animal Blotting, Southern Chromosome Mapping DNA analysis Drosophila melanogaster genetics Female Genes, Lethal Male Nucleic Acid Hybridization Phenotype Receptor, Epidermal Growth Factor genetics Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0055087 91227907 1902987 1991 06 11 1991 06 11 2000 12 18

0036-8075 252 5007 1991 May 10 Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. 833-6 Sex-specific alternative processing of doublesex (dsx) precursor messenger RNA (pre-mRNA) regulates somatic sexual differentiation in Drosophila melanogaster. Cotransfection analyses in which the dsx gene and the female-specific transformer (tra) and transformer-2 (tra-2) complementary DNAs were expressed in Drosophila Kc cells revealed that female-specific splicing of the dsx transcript was positively regulated by the products of the tra and tra-2 genes. Furthermore, analyses of mutant constructs of dsx showed that a portion of the female-specific exon sequence was required for regulation of dsx pre-messenger RNA splicing. Department of Biophysics, Faculty of Science, Kyoto University, Japan. Hoshijima K K Inoue K K Higuchi I I Sakamoto H H Shimura Y Y eng Journal Article

UNITED STATES Science 0404511 0 RNA, Messenger IM dsx tra tra-2 Animal Base Sequence Chromosome Mapping Drosophila melanogaster genetics Gene Expression Regulation Genes, Regulator physiology Genes, Structural physiology Molecular Sequence Data RNA Splicing RNA, Messenger biosynthesis Repetitive Sequences, Nucleic Acid Sex Differentiation physiology Support, Non-U.S. Gov't Transfection FBrf0089823 97032932 8878680 1997 01 28 1997 01 28 2000 12 18

0016-6731 144 1 1996 Sep Differentiation of Muller's chromosomal elements D and E in the obscura group of Drosophila. 139-46 Twenty-two markers located on Muller's elements D or E have been mapped by in situ hybridization in six species of the obscura group of Drosophila and in D. melanogaster. The obscura species can be grouped into a Palearctic cluster (D. subobscura, D. madeirensis and D. guanche) and a Nearctic one (D. pseudoobscura, D. persimilis and D. miranda). Eleven of the probes contain known genes: E74, Acp70A, Est5, hsp28/23, hsp83, emc, hsp70, Xdh, Acph-1, Cec and rp49. The remaining probes are recombinant phages isolated from a D. subobscura genomic library. All these markers hybridize to the putative homologous chromosome or chromosomal arm of elements D and E. Thus, these elements have conserved their genic content during species divergence. Chromosomal homologies proposed previously for each element among the species of the same cluster have been compared with the present results. The distribution of markers within each element has changed considerably as inferred from pairwise comparisons of obscura species included in the two different clusters. Only chromosomal segments defined by closely linked markers have been conserved: one such segment has been detected in element D and three in element E between D subobscura and D. pseudoobscura. Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain. carme@porthos.bio.ub.es Segarra C C Ribó G G Aguadé M M eng Journal Article

UNITED STATES Genetics 0374636 0 Genetic Markers IM Animal Drosophila genetics Drosophila melanogaster genetics Genes, Insect Genetic Markers Support, Non-U.S. Gov't FBrf0134767 21137219 11238934 2001 03 12 2001 04 19 2002 11 01

0270-7306 21 6 2001 Mar Switch in 3' splice site recognition between exon definition and splicing catalysis is important for sex-lethal autoregulation. 1986-96 Maintenance of female sexual identity in Drosophila melanogaster involves an autoregulatory loop in which the protein Sex-lethal (SXL) promotes skipping of exon 3 from its own pre-mRNA. We have used transient transfection of Drosophila Schneider cells to analyze the role of exon 3 splice sites in regulation. Our results indicate that exon 3 repression requires competition between the 5' splice sites of exons 2 and 3 but is independent of their relative strength. Two 3' splice site AG's precede exon 3. We report here that, while the distal site plays a critical role in defining the exon, the proximal site is preferentially used for the actual splicing reaction, arguing for a switch in 3' splice site recognition between exon definition and splicing catalysis. Remarkably, the presence of the two 3' splice sites is important for the efficient regulation by SXL, suggesting that SXL interferes with molecular events occurring between initial splice site communication across the exon and the splice site pairing that leads to intron removal. Gene Expression Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany. Penalva L O LO Lallena M J MJ Valcárcel J J eng Journal Article

United States Mol Cell Biol 8109087 0 Adenine Nucleotides 0 Insect Hormones 0 RNA Splice Sites 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Adenine Nucleotides Alternative Splicing Animal Base Sequence Catalysis Cells, Cultured Drosophila genetics Exons Insect Hormones genetics metabolism Molecular Sequence Data Mutation RNA Splice Sites RNA-Binding Proteins genetics metabolism Support, Non-U.S. Gov't FBrf0137221 21384948 11493541 2001 08 08 2001 09 13 2003 06 16

0950-1991 128 12 2001 Jun The Drosophila tumor suppressor gene lethal(2)giant larvae is required for the emission of the Decapentaplegic signal. 2209-20 The Drosophila tumor suppressor gene lethal(2) giant larvae (lgl) encodes a cytoskeletal protein required for the change in shape and polarity acquisition of epithelial cells, and also for asymmetric division of neuroblasts. We show here that lgl participates in the emission of Decapentaplegic (Dpp), a member of the transforming growth factor beta (TGFbeta) family, in various developmental processes. During embryogenesis, lgl is required for the dpp-dependent transcriptional activation of zipper (zip), which encodes the non-muscle myosin heavy chain (NMHC), in the dorsalmost ectodermal cells - the leading edge cells. The embryonic expression of known targets of the dpp signaling pathway, such as labial or tinman was abolished or strongly reduced in lgl mutants. lgl mutant cuticles exhibited phenotypes resembling those observed in mutated partners of the dpp signaling pathway. In addition, lgl was required downstream of dpp and upstream of its receptor Thickveins (Tkv) for the dorsoventral patterning of the ectoderm. During larval development, the expression of spalt, a dpp target, was abolished in mutant wing discs, while it was restored by a constitutively activated form of Tkv (Tkv(Q253D)). Taking into account that the activation of dpp expression was unaffected in the mutant, this suggests that lgl function is not required downstream of the Dpp receptor. Finally, the function of lgl responsible for the activation of Spalt expression appeared to be required only in the cells that produce Dpp, and lgl mutant somatic clones behaved non autonomously. We therefore position the activity of lgl in the cells that produce Dpp, and not in those that respond to the Dpp signal. These results are consistent with a same role for lgl in exocytosis and secretion as that proposed for its yeast ortholog sro7/77 and lgl might function in parallel or independently of its well-documented role in the control of epithelial cell polarity. Laboratoire de Génétique et de Physiologie du Développement, UMR 6545 CNRS-Université, IBDM CNRS-INSERM-Université de la Méditerranée, Campus de Luminy, 13288 Marseille cedex 09, France. Arquier N N Perrin L L Manfruelli P P Sémériva M M eng Journal Article

England Development 8701744 0 Cytoskeletal Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 Membrane Proteins 0 Myosin Heavy Chains 0 Transcription Factors 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 0 lethal (2) giant larvae protein, Drosophila 0 sal protein 0 zipper protein, Drosophila IM Animal Cytoskeletal Proteins genetics metabolism physiology Drosophila melanogaster embryology genetics metabolism Female Genes, Tumor Suppressor Homeodomain Proteins genetics metabolism Insect Proteins genetics metabolism physiology Male Membrane Proteins genetics metabolism Myosin Heavy Chains genetics metabolism Signal Transduction Support, Non-U.S. Gov't Trans-Activation (Genetics) Transcription Factors genetics metabolism Transcription, Genetic Transforming Growth Factor beta genetics metabolism FBrf0111349 99403009 10471715 1999 10 28 1999 10 28 2002 11 01

0016-6731 153 1 1999 Sep Roles of the C terminus of Armadillo in Wingless signaling in Drosophila. 319-32 Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions and both transduce Wingless (Wg)/Wnt intercellular signals. The current model for Wingless signaling proposes that Armadillo binds the DNA-binding protein dTCF, forming a bipartite transcription factor that activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as a transcriptional activation domain. In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential. We reexamined the function of Armadillo's C terminus in Wingless signaling. We found that C-terminally truncated mutant Armadillo has a deficit in Wg-signaling activity, even when corrected for reduced protein levels. However, we also found that Armadillo proteins lacking all or part of the C terminus retain some signaling ability if overexpressed, and that mutants lacking different portions of the C-terminal domain differ in their level of signaling ability. Finally, we found that the C terminus plays a role in Armadillo protein stability in response to Wingless signal and that the C-terminal domain can physically interact with the Arm repeat region. These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion. Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA. Cox R T RT Pai L M LM Kirkpatrick C C Stein J J Peifer M M eng 5T32 GM-07092 GM NIGMS GM-47857 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Proto-Oncogene Proteins 0 armadillo protein, Drosophila 117758-26-6 wingless protein, Drosophila IM Amino Acid Sequence Animal Binding Sites Cell Membrane metabolism Crosses, Genetic Cytoplasm genetics metabolism Drosophila melanogaster embryology genetics metabolism Extrachromosomal Inheritance Female Genetic Complementation Test Insect Proteins chemistry genetics metabolism Male Models, Biological Molecular Sequence Data Phenotype Proto-Oncogene Proteins metabolism Repetitive Sequences, Amino Acid genetics Sequence Deletion Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0052549 90258833 1692955 1990 06 25 1990 06 25 2000 12 18

0270-7306 10 6 1990 Jun Structure and expression of the Drosophila melanogaster gene for the U1 small nuclear ribonucleoprotein particle 70K protein. 2492-502 A genomic clone encoding the Drosophila U1 small nuclear ribonucleoprotein particle 70K protein was isolated by hybridization with a human U1 small nuclear ribonucleoprotein particle 70K protein cDNA. Southern blot and in situ hybridizations showed that this U1 70K gene is unique in the Drosophila genome, residing at cytological position 27D1,2. Polyadenylated transcripts of 1.9 and 3.1 kilobases were observed. While the 1.9-kilobase mRNA is always more abundant, the ratio of these two transcripts is developmentally regulated. Analysis of cDNA and genomic sequences indicated that these two RNAs encode an identical protein with a predicted molecular weight of 52,879. Comparison of the U1 70K proteins predicted from Drosophila, human, and Xenopus cDNAs revealed 68% amino acid identity in the most amino-terminal 214 amino acids, which include a sequence motif common to many proteins which bind RNA. The carboxy-terminal half is less well conserved but is highly charged and contains distinctive arginine-rich regions in all three species. These arginine-rich regions contain stretches of arginine-serine dipeptides like those found in transformer, transformer-2, and suppressor-of-white-apricot proteins, all of which have been identified as regulators of mRNA splicing in Drosophila melanogaster. Department of Biological Sciences, Columbia University, New York, New York 10027. Mancebo R R Lo P C PC Mount S M SM eng GENBANK M31162 GM 37991 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Oligonucleotide Probes 0 RNA, Messenger 0 Ribonucleoproteins 0 Ribonucleoproteins, Small Nuclear 24937-83-5 Poly A 63231-63-0 RNA 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Blotting, Northern Blotting, Southern Cloning, Molecular Comparative Study DNA genetics Drosophila melanogaster genetics Gene Expression Gene Library Genes, Structural Human Molecular Sequence Data Molecular Weight Oligonucleotide Probes Poly A genetics RNA genetics RNA, Messenger Ribonucleoproteins genetics Ribonucleoproteins, Small Nuclear Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Xenopus FBrf0105786 99088040 9869644 1999 01 22 1999 01 22 2003 08 29

0890-9369 12 24 1998 Dec 15 Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm. 3910-22 Mesodermal progenitors arise in the Drosophila embryo from discrete clusters of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-function and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of unique combinations of intercellular signals. Initially, the intersection between the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two receptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor receptor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By monitoring the expression of the diphosphorylated form of mitogen-associated protein kinase (MAPK), we found that these RTKs are activated in small clusters of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localized RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreover, DER and Htl are differentially involved in the specification of particular progenitors. We conclude that distinct cellular identity codes are generated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in the progressive determination of embryonic mesodermal cells. Centro de Biologia Molecular 'Severo Ochoa', Universidad Autónoma, 28049 Madrid, Spain. Carmena A A Gisselbrecht S S Harrison J J Jiménez F F Michelson A M AM eng Journal Article

UNITED STATES Genes Dev 8711660 0 ESPD protein, E coli 0 Homeodomain Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Receptors, Fibroblast Growth Factor 0 Receptors, Invertebrate Peptide 0 Transcription Factors 0 dpp protein, Drosophila 0 epidermal growth factor receptor homolog, Drosophila 0 lethal of scute protein, Drosophila 108911-13-3 even-skipped protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.112 heartless protein, Drosophila EC 2.7.1.112 htl protein, Drosophila EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 3.6.1.- Proto-Oncogene Protein p21(ras) IM Animal Body Patterning Ca(2+)-Calmodulin Dependent Protein Kinase metabolism Cell Differentiation Drosophila melanogaster cytology embryology genetics Embryonic Induction Epistasis, Genetic Gene Expression Regulation, Developmental Homeodomain Proteins genetics Insect Proteins genetics Mesoderm cytology metabolism Models, Biological Muscles cytology Proto-Oncogene Protein p21(ras) physiology Proto-Oncogene Proteins genetics Receptor, Epidermal Growth Factor physiology Receptors, Fibroblast Growth Factor physiology Receptors, Invertebrate Peptide physiology Signal Transduction Stem Cells cytology Support, Non-U.S. Gov't Transcription Factors genetics FBrf0129826 20469352 11014813 2000 10 25 2000 11 30

0016-6731 156 2 2000 Oct A screen for new trithorax group genes identified little imaginal discs, the Drosophila melanogaster homologue of human retinoblastoma binding protein 2. 645-63 The proteins encoded by two groups of conserved genes, the Polycomb and trithorax groups, have been proposed to maintain, at the level of chromatin structure, the expression pattern of homeotic genes during Drosophila development. To identify new members of the trithorax group, we screened a collection of deficiencies for intergenic noncomplementation with a mutation in ash1, a trithorax group gene. Five of the noncomplementing deletions uncover genes previously classified as members of the Polycomb group. This evidence suggests that there are actually three groups of genes that maintain the expression pattern of homeotic genes during Drosophila development. The products of the third group appear to be required to maintain chromatin in both transcriptionally inactive and active states. Six of the noncomplementing deficiencies uncover previously unidentified trithorax group genes. One of these deficiencies removes 25D2-3 to 26B2-5. Within this region, there are two, allelic, lethal P-insertion mutations that identify one of these new trithorax group genes. The gene has been called little imaginal discs based on the phenotype of mutant larvae. The protein encoded by the little imaginal discs gene is the Drosophila homologue of human retinoblastoma binding protein 2. Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA. Gildea J J JJ Lopez R R Shearn A A eng GM53058 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Carrier Proteins 0 Chromatin 0 Insect Proteins 0 Repressor Proteins 0 Retinoblastoma Protein 134549-01-2 Polycomb protein, insect 139532-75-5 retinoblastoma binding protein 2 IM Animal Carrier Proteins genetics Chromatin genetics Crosses, Genetic Drosophila melanogaster anatomy & histology genetics growth & development Female Genes, Homeobox Genes, Lethal Genotype Human Insect Proteins genetics Male Repressor Proteins genetics Retinoblastoma Protein metabolism Support, U.S. Gov't, P.H.S. Suppression, Genetic Thorax Transcription, Genetic FBrf0055486 95194373 1365904 1995 04 10 1995 04 10 2000 12 18

0265-9247 14 8 1992 Aug How do germ cells choose their sex? Drosophila as a paradigm. 513-8 Sex determination in the germ line may either rely on cell-autonomous genetic information, or it may be imposed during development by inductive somatic signals. In Drosophila, both mechanisms contribute to ensure that germ cells are oogenic when differentiating in females and spermatogenic when differentiating in males. Some of the genes that are involved in germ line sex determination have been identified. In other species, including vertebrates, inductive signals are commonly used to determine the sex of germ cells. Zoological Institute, University of Zurich, Switzerland. Steinmann-Zwicky M M eng Journal Article Review Review, Tutorial

ENGLAND Bioessays 8510851 IM Sxl da dsx fl(2)d fs(l)1621 ix liz ovo sis-a sis-b snf tra tra-2 Animal Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian cytology Embryonic Induction Female Gene Expression Regulation, Developmental Genotype Germ Cells physiology Insects physiology Male Mammals physiology Sex Determination (Analysis) Species Specificity Support, Non-U.S. Gov't X Chromosome Y Chromosome 40 FBrf0149190 22075719 12079765 2002 06 24 2002 08 14

0166-2236 25 7 2002 Jul Interactive nervous system development: control of cell survival in Drosophila. 365-70 The non-autonomous control of cell survival has long been thought to be a mechanism of adjusting cell populations in the vertebrate nervous system, enabling connectivity and myelination to produce a functional brain. Despite cellular evidence that analogous mechanisms occur in invertebrates, scepticism has long reigned over whether they operate in model organisms such as Drosophila. This has led to speculation that there are inherent differences between the development and evolution of simple brains and the brains of vertebrates. The great paradox has, until recently, been the absence of molecular evidence of trophic factors in Drosophila. Recent data have finally shown that EGFR (epidermal-growth-factor receptor) ligands function in the Drosophila CNS to maintain glial survival. Trophic interactions are, thus, a general mechanism of nervous system development. Neurodevelopment Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK. a.hidalgo@gen.cam.ac.uk Hidalgo Alicia A eng Journal Article Review Review, Tutorial

England Trends Neurosci 7808616 0 Nerve Growth Factors EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Body Patterning physiology Cell Communication physiology Cell Differentiation physiology Cell Survival physiology Drosophila melanogaster cytology embryology metabolism Nerve Growth Factors genetics metabolism Nervous System cytology embryology metabolism Neuroglia cytology metabolism Neurons cytology metabolism Receptor, Epidermal Growth Factor genetics metabolism Support, Non-U.S. Gov't 80 FBrf0091008 97138160 8985186 1997 01 23 1997 01 23 2002 11 01

0890-9369 10 24 1996 Dec 15 Segmentation and specification of the Drosophila mesoderm. 3183-94 Patterning of the developing mesoderm establishes primordia of the visceral, somatic, and cardiac tissues at defined anteroposterior and dorsoventral positions in each segment. Here we examine the mechanisms that locate and determine these primordia. We focus on the regulation of two mesodermal genes: bagpipe (bap), which defines the anlagen of the visceral musculature of the midgut, and serpent (srp), which marks the anlagen of the fat body. These two genes are activated in specific groups of mesodermal cells in the anterior portions of each parasegment. Other genes mark the anlagen of the cardiac and somatic mesoderm and these are expressed mainly in cells derived from posterior portions of each parasegment. Thus the parasegments appear to be subdivided, at least with respect to these genes, a subdivision that depends on pair-rule genes such as even-skipped (eve). We show with genetic mosaics that eve acts autonomously within the mesoderm. We also show that hedgehog (hh) and wingless (wg) mediate pair-rule gene functions in the mesoderm, probably partly by acting within the mesoderm and partly by inductive signaling from the ectoderm. hh is required for the normal activation of bap and srp in anterior portions of each parasegment, whereas wg is required to suppress bap and srp expression in posterior portions. Hence, hh and wg play opposing roles in mesoderm segmentation. Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA. Azpiazu N N Lawrence P A PA Vincent J P JP Frasch M M eng HD30832 HD NICHD Journal Article

UNITED STATES Genes Dev 8711660 0 Insect Proteins 0 Proteins 0 Proto-Oncogene Proteins 0 armadillo protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Drosophila melanogaster embryology Gastrula Gene Expression Regulation, Developmental Genes, Homeobox Insect Proteins physiology Mesoderm cytology Morphogenesis Proteins physiology Proto-Oncogene Proteins physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0102840 98250680 9584093 1998 07 07 1998 07 07 2000 12 18

0016-6731 149 1 1998 May Mapping of Drosophila mutations using site-specific male recombination. 157-63 Although recombination does not usually occur in the male Drosophila germline, site-specific recombination can be induced at the ends of P elements. This finding suggested that male recombination could be used to map Drosophila mutations. In this article, we describe the general method and its application to the mapping of two EMS-induced female-sterile mutations, grauzone and cortex. Within two months, the grauzone gene was mapped relative to seven different P-element insertion sites, and cortex was mapped relative to 23 different P-elements. The results allowed us to map grauzone to a region of about 50 kb, and cortex distal to the chromosomal region 33E. These experiments demonstrate that P-element-induced site-specific male recombination is an efficient and general method to map Drosophila autosomal mutations. Department of Pharmacology, Institute for Cell and Developmental Biology, University at Stony Brook, Stony Brook, New York 11794-8651, USA. Chen B B Chu T T Harms E E Gergen J P JP Strickland S S eng GM-51584 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements IM Animal Chromosome Mapping DNA Transposable Elements genetics Drosophila melanogaster genetics Male Meiosis genetics Mutation Recombination, Genetic Support, U.S. Gov't, P.H.S. FBrf0093549 97302964 9159395 1997 06 12 1997 06 12 2001 11 02

0890-9369 11 9 1997 May 1 Requirement for Drosophila 14-3-3 zeta in Raf-dependent photoreceptor development. 1140-7 Based on biochemical and functional data obtained with tissue culture cells and yeast, 14-3-3 proteins have been implicated in a number of different signal transduction processes, in particular in the signal-dependent activation of protein kinases. We performed a functional analysis of 14-3-3 in a multicellular organism, initiated by the cloning of a 14-3-3 zeta homolog of Drosophila melanogaster, termed D14-3-3 zeta. D14-3-3 zeta transcripts are strongly enriched in the developing central nervous system. In addition, they are predominantly expressed in the region posterior to the morphogenetic furrow of the eye imaginal disc where cells differentiate as photoreceptors. In these cells D14-3-3 zeta is localized apically. Both the expression pattern and the subcellular localization are consistent with the proposed function of 14-3-3 proteins in Ras/Raf/MAPK signaling. D14-3-3 zeta mutant analysis combined with rescue experiments involving gain-of-function alleles of Raf and Ras indicate that D14-3-3 zeta is an essential component of the Raf/Ras signaling pathway and necessary for photoreceptor differentiation. It acts upstream of Raf and downstream of Ras. European Molecular Biology Laboratory, Heidelberg, Germany. Kockel L L Vorbrüggen G G Jäckle H H Mlodzik M M Bohmann D D eng GENBANK Y12573 Journal Article

UNITED STATES Genes Dev 8711660 0 14-3-3 protein 0 DNA, Complementary 0 Proteins 0 Proto-Oncogene Proteins EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Alleles Amino Acid Sequence Animal Animals, Genetically Modified Base Sequence Cloning, Molecular DNA, Complementary genetics Drosophila genetics growth & development physiology Gene Expression Regulation, Developmental Genes, Insect Genes, ras Molecular Sequence Data Mutation Photoreceptors, Invertebrate growth & development physiology Protein-Serine-Threonine Kinases genetics physiology Proteins genetics physiology Proto-Oncogene Proteins genetics physiology Proto-Oncogene Proteins c-raf Signal Transduction Support, Non-U.S. Gov't FBrf0088926 96262192 8676882 1996 08 12 1996 08 12 2000 12 18

0026-8925 251 3 1996 Jun 12 A newly identified Minute locus, M(2)32D, encodes the ribosomal protein L9 in Drosophila melanogaster. 381-7 A gene encoding a ubiquitously expressed mRNA in Drosophila melanogaster was isolated and identified as the gene for ribosomal protein L9 (rpL9) by its extensive sequence homology to the corresponding gene from rat. The rpL9 gene is localized in polytene region 32D where two independent P element insertions flanking the locus are available. Remobilization of either P element generated lines with a typical Minute phenotype, e.g. thin and short bristles, prolonged development, and female semisterility in heterozygotes as well as homozygous lethality. All these characteristics can be rescued when a 3.9 kb restriction fragment containing the rpL9 gene is reintroduced by P element-mediated germline transformation. This result confirms that M(2)32D codes for ribosomal protein L9. Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Germany. Schmidt A A Hollmann M M Schäfer U U eng GENBANK X94613 Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA Transposable Elements 0 RNA, Messenger 0 Ribosomal Proteins 0 ribosomal protein L9 IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Molecular methods DNA Transposable Elements Drosophila melanogaster genetics Female Genes, Structural, Insect genetics Genotype Molecular Sequence Data Phenotype RNA, Messenger analysis Rats Ribosomal Proteins genetics Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't Transformation, Genetic FBrf0082581 95311995 7791801 1995 07 27 1995 07 27 2000 12 18

0270-7306 15 7 1995 Jul The decapentaplegic core promoter region plays an integral role in the spatial control of transcription. 3960-8 The Drosophila melanogaster decapentaplegic (dpp) gene encodes a transforming growth factor beta-related cell signaling molecule that plays a critical role in dorsal/ventral pattern formation. The dpp expression pattern in the Drosophila embryo is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, phases II and III, in which dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III), depend on multiple independent elements in the dpp 5'-flanking region. Several aspects of the normal dpp expression pattern appear to depend on the unique properties of the dpp core promoter. For example, this core promoter (extending from -22 to +6) is able to direct a phase II expression pattern in the absence of additional upstream or downstream regulatory elements. In addition, a ventral-specific enhancer in the dpp 5'-flanking region that binds the Dorsal factor activates the heterologous hsp70 core promoter but not the dpp core promoter. Thus, the dpp core promoter region may contribute to spatially regulated transcription both by interacting directly with spatially restricted activators and by modifying the activity of proteins bound to enhancer elements. Department of Chemistry and Biochemistry, University of California, Los Angeles 90095-1569, USA. Schwyter D H DH Huang J D JD Dubnicoff T T Courey A J AJ eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA-Binding Proteins 0 Insect Hormones 0 Transcription Factors 0 dpp protein, Drosophila IM Animal Base Sequence Blastoderm DNA Mutational Analysis DNA-Binding Proteins metabolism Drosophila embryology genetics Embryonic Induction Enhancer Elements (Genetics) genetics Gene Expression Regulation Insect Hormones genetics Molecular Sequence Data Promoter Regions (Genetics) genetics Protein Binding Sequence Deletion Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Transcription, Genetic FBrf0085625 96084708 8526885 1996 01 25 1996 01 25 2000 12 18

0265-9247 17 11 1995 Nov The anterior-posterior and dorsal-ventral axes have a common origin in Drosophila melanogaster. 920-2 The mechanisms governing anterior-posterior and dorsal-ventral polarity in Drosophila melanogaster had previously been considered as independent processes. However, two papers(1,2) now reveal that both axes are initiated during oogenesis by the same pathway, and also clearly demonstrate that one is dependent on the other. Waksman Institute, Piscataway, New Jersey 08855-0759, USA. Munn K K Steward R R eng Journal Article Review Review, Tutorial

ENGLAND Bioessays 8510851 IM Animal Cell Polarity Drosophila melanogaster cytology embryology genetics Female Oogenesis Signal Transduction 22 FBrf0108102 99160564 10049923 1999 05 06 1999 05 06 2002 11 01

0016-6731 151 3 1999 Mar Genetic analysis of viable Hsp90 alleles reveals a critical role in Drosophila spermatogenesis. 1065-79 The Hsp90 chaperone protein maintains the activities of a remarkable variety of signal transducers, but its most critical functions in the context of the whole organism are unknown. Point mutations of Hsp83 (the Drosophila Hsp90 gene) obtained in two different screens are lethal as homozygotes. We report that eight transheterozygous mutant combinations produce viable adults. All exhibit the same developmental defects: sterile males and sterile or weakly fertile females. We also report that scratch, a previously identified male-sterile mutation, is an allele of Hsp82 with a P-element insertion in the intron that reduces expression. Thus, it is a simple reduction in Hsp90 function, rather than possible altered functions in the point mutants, that leads to male sterility. As shown by light and electron microscopy, all stages of spermatogenesis involving microtubule function are affected, from early mitotic divisions to later stages of sperm maturation, individualization, and motility. Aberrant microtubules are prominent in yeast cells carrying mutations in HSP82 (the yeast Hsp90 gene), confirming that Hsp90 function is connected to microtubule dynamics and that this connection is highly conserved. A small fraction of Hsp90 copurifies with taxol-stabilized microtubule proteins in Drosophila embryo extracts, but Hsp90 does not remain associated with microtubules through repeated temperature-induced assembly and disassembly reactions. If the spermatogenesis phenotypes are due to defects in microtubule dynamics, we suggest these are indirect, reflecting a role for Hsp90 in maintaining critical signal transduction pathways and microtubule effectors, rather than a direct role in the assembly and disassembly of microtubules themselves. Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA. Yue L L Karr T L TL Nathan D F DF Swift H H Srinivasan S S Lindquist S S eng Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Heat-Shock Proteins 0 Heat-Shock Proteins 70 0 Heat-Shock Proteins 90 0 TATA-Box Binding Protein 0 Transcription Factors 0 Tubulin 0 heat-shock protein 83 IM Alleles Animal Crosses, Genetic DNA-Binding Proteins immunology Drosophila melanogaster genetics physiology Female Fertility genetics Fluorescent Antibody Technique Genes, Insect Heat-Shock Proteins genetics Heat-Shock Proteins 70 genetics Heat-Shock Proteins 90 genetics physiology Male Meiosis Microtubules genetics physiology Models, Biological Phenotype Point Mutation Spermatids ultrastructure Spermatocytes ultrastructure Spermatogenesis genetics physiology Spermatozoa ultrastructure Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. TATA-Box Binding Protein Temperature Testis cytology ultrastructure Transcription Factors immunology Tubulin genetics immunology Yeasts genetics FBrf0056153 92380469 1511868 1992 09 29 1992 09 29 2000 12 18

0016-6723 59 3 1992 Jun The segmentation gene runt is needed to activate Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila. 189-98 In Drosophila, sex is determined by the relative number of X chromosomes to autosomal sets (X:A ratio). The amount of products from several X-linked genes, called sisterless elements, is used to indicate to Sex-lethal the relative number of X chromosomes present in the cell. In response to the X:A signal, Sex-lethal is activated in females but remains inactive in males, being responsible for the control of both sex determination and dosage compensation. Here we find that the X-linked segmentation gene runt plays a role in this process. Reduced function of runt results in female-specific lethality and sexual transformation of XX animals that are heterozygous for Sxl or sis loss-of-function mutations. These interactions are suppressed by SxlM1, a mutation that constitutively expresses female Sex-lethal functions, and occur at the time when the X:A signal determines Sex-lethal activity. Moreover, the presence of a loss-of-function runt mutation masculinizes triploid intersexes. On the other hand, runt duplications cause a reduction in male viability by ectopic activation of Sex-lethal. We conclude that runt is needed for the initial step of Sex-lethal activation, but does not have a major role as an X-counting element. Centro de Investigaciones Biologicas, Madrid, Spain. Torres M M Sánchez L L eng Journal Article

ENGLAND Genet Res 0370741 IM Sex-lethal runt Animal Dosage Compensation (Genetics) Drosophila melanogaster genetics Female Gene Expression Regulation physiology Male Sex Determination (Analysis) Support, Non-U.S. Gov't FBrf0128619 20279982 10818133 2000 06 15 2000 06 15 2001 05 18

1529-2401 20 11 2000 Jun 1 Role of cAMP cascade in synaptic stability and plasticity: ultrastructural and physiological analyses of individual synaptic boutons in Drosophila memory mutants. 3980-92 Mutations of the genes rutabaga (rut) and dunce (dnc) affect the synthesis and degradation of cAMP, respectively, and disrupt learning in Drosophila. Combined ultrastructural analysis and focal electrophysiological recording in the larval neuromuscular junction revealed a loss of stability and fine tuning of synaptic structure and function in both mutants. Increased ratios of docked/undocked vesicles and poorly defined synaptic specializations characterized dnc synapses. In contrast, rut boutons possessed fewer, although larger, synapses with lower proportions of docked vesicles. At reduced Ca(2+) levels, decreased quantal content coupled with an increase in failure rate was seen in rut boutons and reduced pair-pulse facilitation were found in both rut and dnc mutants. At physiological Ca(2+) levels, strong enhancement, instead of depression, in evoked release was observed in some dnc and rut boutons during 10 Hz tetanus. Furthermore, increased variability of synaptic transmission, including fluctuation and asynchronicity of evoked release, paralleled an increase in synapse size variation in both dnc and rut boutons, which might impose problems for effective signal processing in the nervous system. Pharmacological and genetic studies indicated broader ranges of physiological alteration by dnc and rut mutations than either the acute effects of cAMP analogs or the available mutations that affect cAMP-dependent protein kinase (PKA) activity. This is consistent with previous reports of more severe learning defects in dnc and rut mutations than these PKA mutants and allows identification of the phenotypes involving long-term developmental regulation and those conferred by PKA. Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52240, USA. Renger J J JJ Ueda A A Atwood H L HL Govind C K CK Wu C F CF eng Journal Article

UNITED STATES J Neurosci 8102140 60-92-4 Cyclic AMP IM Alleles Animal Axons physiology ultrastructure Cell Count Cyclic AMP physiology Drosophila melanogaster Electric Stimulation Larva Memory physiology Microscopy, Electron Muscles innervation Mutation genetics Neuromuscular Junction physiology ultrastructure Neuronal Plasticity physiology Phenotype Presynaptic Terminals physiology ultrastructure Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Synapses physiology ultrastructure FBrf0141064 21149363 11253649 2001 03 19 2001 03 29

1471-0056 1 2 2000 Nov Sticking together and sorting things out: adhesion as a force in development. 100-8 During development it is not sufficient for cells to differentiate properly--they must also become physically grouped into appropriate structures, to form skin on the outside, and blood and muscle on the inside. How does this three-dimensional patterning occur? One classic explanation for this resolution of cells and tissues into distinct three-dimensional structures has been that as cells differentiate, they develop differential adhesive properties, and that these affinity differences allow cells to sort out from one another. This classic hypothesis is being investigated with increasing intensity, as recent work on the Drosophila wing and the vertebrate brain has shown that signalling between tissues is essential for the establishment of differential affinities. Developmental Patterning Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. h.mcneill@icrf.icnet.uk McNeill H H eng Journal Article Review Review, Academic

England Nat Rev Genet 100962779 0 Cadherins IM Animal Body Patterning Cadherins physiology Cell Adhesion Cell Differentiation Drosophila melanogaster Female Morphogenesis Oocytes physiology Signal Transduction Vertebrates 73 FBrf0059278 93317612 8327474 1993 08 06 1993 08 06 2000 12 18

0027-8424 90 13 1993 Jul 1 Drosophila transforming growth factor beta superfamily proteins induce endochondral bone formation in mammals. 6004-8 Both decapentaplegic (dpp) protein and 60A protein have been implicated in pattern formation during Drosophila melanogaster embryogenesis. Within the C-terminal domain, dpp and 60A are similar to human bone morphogenetic protein 2 (75% identity) and human osteogenic protein 1 (70% identity), respectively. Both recombinant human bone morphogenetic protein 2 and recombinant human osteogenic protein 1 have been shown to induce bone formation in vivo and to restore large diaphyseal segmental defects in various animal models. We examined whether the Drosophila proteins, dpp and 60A, have the capacity to induce bone formation in mammals by using the rat subcutaneous bone induction model. Highly purified recombinant dpp and 60A induced the formation of cartilage, bone, and bone marrow in mammals, as determined by histological observations and by measurements of the specific activity of alkaline phosphatase and calcium content of the implants, thereby demonstrating that related proteins from phylogenetically distant species are capable of inducing bone formation in mammals when placed in sites where progenitor cells are available. Creative BioMolecules, Inc., Hopkinton, MA 01748. Sampath T K TK Rashka K E KE Doctor J S JS Tucker R F RF Hoffmann F M FM eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Bone Morphogenetic Proteins 0 Insect Hormones 0 Proteins 0 Recombinant Proteins 0 Transforming Growth Factor beta 0 bone morphogenetic protein 7 0 dpp protein, Drosophila IM Amino Acid Sequence Animal Bone Development drug effects Bone Morphogenetic Proteins Human Insect Hormones pharmacology Molecular Sequence Data Proteins pharmacology Rats Recombinant Proteins pharmacology Transforming Growth Factor beta pharmacology FBrf0134754 21143055 11230529 2001 03 14 2001 06 14

0737-4038 18 3 2001 Mar Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. 279-90 Surveys of molecular variation in Drosophila melanogaster and Drosophila simulans have suggested that diversity outside of Africa is a subset of that within Africa. It has been argued that reduced levels of diversity in non-African populations reflect a population bottleneck, adaptation to temperate climates, or both. Here, I summarize the available single-nucleotide polymorphism data for both species. A simple "out of Africa" bottleneck scenario is consistent with geographic patterns for loci on the X chromosome but not with loci on the autosomes. Interestingly, there is a trend toward lower nucleotide diversity on the X chromosome relative to autosomes in non-African populations of D. melanogaster, but the opposite trend is seen in African populations. In African populations, autosomal inversion polymorphisms in D. melanogaster may contribute to reduced autosome diversity relative to the X chromosome. To elucidate the role that selection might play in shaping patterns of variability, I present a summary of within- and between-species patterns of synonymous and replacement variation in both species. Overall, D. melanogaster autosomes harbor an excess of amino acid replacement polymorphisms relative to D. simulans. Interestingly, range expansion from Africa appears to have had little effect on synonymous-to-replacement polymorphism ratios. Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, Scotland. peter.andolfatto@ed.ac.uk Andolfatto P P eng Journal Article

United States Mol Biol Evol 8501455 0 Nucleotides IM Animal Drosophila genetics Evolution Inversion (Genetics) Linkage (Genetics) Nucleotides genetics Polymorphism (Genetics) Species Specificity Support, Non-U.S. Gov't Variation (Genetics) X Chromosome FBrf0151275 22153224 12163402 2002 08 06 2002 09 23 2002 11 01

0950-1991 129 17 2002 Sep Interaction between EGFR signaling and DE-cadherin during nervous system morphogenesis. 3983-94 Dynamically regulated cell adhesion plays an important role during animal morphogenesis. Here we use the formation of the visual system in Drosophila embryos as a model system to investigate the function of the Drosophila classic cadherin, DE-cadherin, which is encoded by the shotgun (shg) gene. The visual system is derived from the optic placode which normally invaginates from the surface ectoderm of the embryo and gives rise to two separate structures, the larval eye (Bolwig's organ) and the optic lobe. The optic placode dissociates and undergoes apoptotic cell death in the absence of DE-cadherin, whereas overexpression of DE-cadherin results in the failure of optic placode cells to invaginate and of Bolwig's organ precursors to separate from the placode. These findings indicate that dynamically regulated levels of DE-cadherin are essential for normal optic placode development. It was shown previously that overexpression of DE-cadherin can disrupt Wingless signaling through titration of Armadillo out of the cytoplasm to the membrane. However, the observed defects are likely the consequence of altered DE-cadherin mediated adhesion rather than a result of compromising Wingless signaling, as overexpression of a DE-cadherin-alpha-catenin fusion protein, which lacks Armadillo binding sites, causes similar defects as DE-cadherin overexpression. We further studied the genetic interaction between DE-cadherin and the Drosophila EGF receptor homolog, EGFR. If EGFR function is eliminated, optic placode defects resemble those following DE-cadherin overexpression, which suggests that loss of EGFR results in an increased adhesion of optic placode cells. An interaction between EGFR and DE-cadherin is further supported by the finding that expression of a constitutively active EGFR enhances the phenotype of a weak shg mutation, whereas a mutation in rhomboid (rho) (an activator of the EGFR ligand Spitz) partially suppresses the shg mutant phenotype. Finally, EGFR can be co-immunoprecipitated with anti-DE-cadherin and anti-Armadillo antibodies from embryonic protein extracts. We propose that EGFR signaling plays a role in morphogenesis by modulating cell adhesion. Department of Molecular Cell and Developmental Biology, University of California Los Angeles, 90095, USA. Dumstrei Karin K Wang Fay F Shy Diana D Tepass Ulrich U Hartenstein Volker V eng NS 29367 NS NINDS Journal Article

England Development 8701744 0 Cadherins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 armadillo protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Apoptosis physiology Cadherins physiology Drosophila melanogaster Ectoderm metabolism Eye embryology Ganglia, Invertebrate embryology metabolism Insect Proteins metabolism Morphogenesis physiology Nervous System embryology Proto-Oncogene Proteins metabolism Receptor, Epidermal Growth Factor physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0047306 88042799 3118464 1987 12 03 1987 12 03 2000 12 18

0036-8075 238 4827 1987 Oct 30 Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. 692-4 The Drosophila gene, dorsal, is a maternal effect locus that is essential for the establishment of dorsal-ventral polarity in the developing embryo. The dorsal protein was predicted from the complementary DNA sequence; it is almost 50 percent identical, over an extensive region, to the protein encoded by the avian oncogene v-rel, its cellular homolog, c-rel, and a human c-rel fragment. The oncogene v-rel is highly oncogenic in avian lymphoid, spleen, and bone marrow cells. Department of Biology, Princeton University, NJ 08544. Steward R R eng GENBANK M23702 Journal Article

UNITED STATES Science 0404511 0 Proto-Oncogene Proteins 9007-49-2 DNA IM Amino Acid Sequence Animal DNA genetics Drosophila melanogaster embryology genetics Genes, Structural Molecular Sequence Data Morphogenesis Oogenesis Proto-Oncogene Proteins genetics Proto-Oncogenes Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0043895 87002474 3093080 1986 11 07 1986 11 07 2000 12 18

0092-8674 46 7 1986 Sep 26 Alternative 5' exons and tissue-specific expression of the Drosophila EGF receptor homolog transcripts. 1091-101 cDNA clones of the Drosophila epidermal growth factor receptor homolog (DER) gene were isolated and sequenced. The deduced amino acid sequence shows a similar degree of homology to the human epidermal growth factor receptor and to the rat and human neu proteins; the most striking difference is the addition of a third cysteine-rich extracellular domain in DER. The structure of the cDNA indicates the use of alternative 5' exons. Thus, the gene encodes three putative proteins differing at their N termini. The distribution of DER transcripts was analyzed by in situ hybridization. Transcripts are uniformly distributed in embryos, larval transcripts are primarily localized to proliferating tissues of the imaginal discs and brain cortex, and adult transcripts are detected mainly in the brain and ganglia. All three splicing alternatives show similar tissue distribution during development. Schejter E D ED Segal D D Glazer L L Shilo B Z BZ eng GENBANK K03416 K03417 K03418 Journal Article

UNITED STATES Cell 0413066 52-90-4 Cysteine 9007-49-2 DNA EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Age Factors Amino Acid Sequence Animal Base Sequence Cloning, Molecular Comparative Study Cysteine DNA genetics Drosophila melanogaster embryology genetics growth & development Exons Gene Expression Regulation Genes, Structural RNA Splicing Receptor, Epidermal Growth Factor genetics Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Tissue Distribution Transcription, Genetic FBrf0054129 91200601 1901816 1991 05 17 1991 05 17 2000 12 18

0016-6731 127 1 1991 Jan The doublesex locus of Drosophila melanogaster and its flanking regions: a cytogenetic analysis. 125-38 The region of the third chromosome (84D-F) of Drosophila melanogaster that contains the doublesex (dsx) locus has been cytogenetically analyzed. Twenty nine newly induced, and 42 preexisting rearrangements broken in dsx and the regions flanking dsx have been cytologically and genetically characterized. These studies established that the dsx locus is in salivary chromosome band 84E1-2. In addition, these observations provide strong evidence that the dsx locus functions only to regulate sexual differentiation and does not encode a vital function. To obtain new alleles at the dsx locus and to begin to analyze the genes flanking dsx, 59 lethal and visible mutations in a region encompassing dsx were induced. These mutations together with preexisting mutations in the region were deficiency mapped and placed into complementation groups. Among the mutations we isolated, four new mutations affecting sexual differentiation were identified. All proved to be alleles of dsx, suggesting that dsx is the only gene in this region involved in regulating sexual differentiation. All but one of the new dsx alleles have equivalent effects in males and females. The exception, dsxEFH55, strongly affects female sexual differentiation, but only weakly affects male sexual differentiation. The interactions of dsxEFH55 with mutations in other genes affecting sexual differentiation are described. These results are discussed in terms of the recent molecular findings that the dsx locus encodes sex-specific proteins that share in common their amino termini but have different carboxyl termini. The 72 mutations in this region that do not affect sexual differentiation identify 25 complementation groups. A translocation, T(2;3)Es that is associated with a lethal allele in one of these complementation groups is also broken at the engrailed (en) locus on the second chromosome and has a dominant phenotype that may be due to the expression of en in the anterior portion of the abdominal tergites where en is not normally expressed. The essential genes found in the 84D-F region are not evenly distributed throughout this region; most strikingly the 84D1-11 region appears to be devoid of essential genes. It is suggested that the lack of essential genes in this region is due to the region (1) containing genes with nonessential functions and (2) being duplicated, possibly both internally and elsewhere in the genome. Biology Department, University of California, San Diego 92093. Baker B S BS Hoff G G Kaufman T C TC Wolfner M F MF Hazelrigg T T eng Journal Article

UNITED STATES Genetics 0374636 IM dsx Alleles Animal Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics radiation effects Female Gene Rearrangement Genes, Lethal Genes, Regulator Genetic Complementation Test Male Mutagenesis Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0086696 96194044 8631263 1996 07 02 1996 07 02 2002 11 01

0950-1991 122 3 1996 Mar decapentaplegic, a target gene of the wingless signalling pathway in the Drosophila midgut. 849-58 dishevelled, shaggy/zeste-white 3 and armadillo are required for transmission of the wingless signal in the Drosophila epidermis. We show that these genes act in the same epistatic order in the embryonic midgut to transmit the wingless signal. In addition to mediating transcriptional stimulation of the homeotic genes Ultrabithorax and labial, they are also required for transcriptional repression of labial by high wingless levels. Efficient labial expression thus only occurs within a window of intermediate wingless pathway activity. Finally, the shaggy/zeste-white 3 mutants revealed that wingless signalling can stimulate decapentaplegic transcription in the absence of Ultrabithorax, identifying decapentaplegic as a target gene of wingless. As decapentaplegic itself is required for wingless expression in the midgut, this represents a positive feed-back loop between two cell groups signalling to each other to stimulate each other's signal production. MRC Laboratory of Molecular Biology, Cambridge, UK. Yu X X Hoppler S S Eresh S S Bienz M M eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Dsh protein 0 Homeodomain Proteins 0 Insect Hormones 0 Proteins 0 Proto-Oncogene Proteins 0 RNA, Messenger 0 armadillo protein, Drosophila 0 dpp protein, Drosophila 0 ultrabithorax protein 117758-26-6 wingless protein, Drosophila 125388-07-0 lab protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 shaggy kinase, Drosophila IM Animal DNA-Binding Proteins physiology Drosophila melanogaster embryology Embryonic Induction Endoderm cytology Epistasis, Genetic Gene Expression Regulation, Developmental Homeodomain Proteins physiology Insect Hormones physiology Intestines embryology Morphogenesis Protein-Serine-Threonine Kinases physiology Proteins physiology Proto-Oncogene Proteins physiology RNA, Messenger genetics Signal Transduction FBrf0046290 88112828 3123323 1988 03 04 1988 03 04 2000 12 18

0890-9369 1 8 1987 Oct The decapentaplegic gene is required for dorsal-ventral patterning of the Drosophila embryo. 868-79 The decapentaplegic gene (dpp), which encodes a growth factor-like protein (Padgett et al. 1987), is implicated in several morphogenetic events in Drosophila melanogaster. We define here a novel embryonic function encoded by dppHin+ alleles of the dpp gene. dppHin null homozygotes die as ventralized embryos. dppHin activity is not required in the maternal germ line since lack of dppHin function during oogenesis has no effect on the zygotic phenotype. Since dppHin null embryos are already abnormal early in gastrulation, the dppHin product is an early-acting, strictly zygotic function involved in establishing the embryonic dorsal-ventral pattern. Several maternally acting dorsalizing genes are thought to be required for the establishment of a dorsal-ventral morphogenetic gradient (Anderson et al. 1985b). We have examined the interactions of dppHin mutations with three of these genes. Embryos null for dppHin and derived from a mother homozygous for a dorsalizing mutation exhibit a lateralized phenotype, indicating that the dorsal-ventral identity of the epidermis in part derives from the direct or indirect regulation of dppHin activity by these genes. Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138-2097. Irish V F VF Gelbart W M WM eng GM 28669 GM NIGMS Journal Article

UNITED STATES Genes Dev 8711660 0 Growth Substances 0 Proteins IM Animal Chromosome Mapping Drosophila melanogaster embryology genetics Embryo, Nonmammalian Female Genes, Lethal Genes, Structural Growth Substances genetics Morphogenesis Mutation Proteins genetics Recombination, Genetic Support, U.S. Gov't, P.H.S. FBrf0093078 97265426 9111363 1997 05 15 1997 05 15 2002 09 23

0270-7306 17 5 1997 May Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2. 2908-19 Sex determination in Drosophila melanogaster is regulated by a cascade of splicing factors which direct the sex-specific expression of gene products needed for male and female differentiation. The splicing factor TRA-2 affects sex-specific splicing of multiple pre-mRNAs involved in sexual differentiation. The tra-2 gene itself expresses a complex set of mRNAs generated through alternative processing that collectively encode three distinct protein isoforms. The expression of these isoforms differs in the soma and germ line. In the male germ line the ratio of two isoforms present is governed by autoregulation of splicing. However, the functional significance of multiple TRA-2 isoforms has remained uncertain. Here we have examined whether the structure, function, and regulation of tra-2 are conserved in Drosophila virilis, a species diverged from D. melanogaster by over 60 million years. We find that the D. virilis homolog of tra-2 produces alternatively spliced RNAs encoding a set of protein isoforms analogous to those found in D. melanogaster. When introduced into the genome of D. melanogaster, this homolog can functionally replace the endogenous tra-2 gene for both normal female sexual differentiation and spermatogenesis. Examination of alternative mRNAs produced in D. virilis testes suggests that germ line-specific autoregulation of tra-2 function is accomplished by a strategy similar to that used in D. melanogaster. The similarity in structure and function of the tra-2 genes in these divergent Drosophila species supports the idea that sexual differentiation in D. melanogaster and D. virilis is accomplished under the control of similar regulatory pathways. Department of Molecular Genetics, M.D. Anderson Cancer Center, University of Texas, Houston 77030, USA. Chandler D D McGuffin M E ME Piskur J J Yao J J Baker B S BS Mattox W W eng GENBANK U72682 CA09299-18 CA NCI CA16672 CA NCI GM 50825 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA-Binding Proteins 0 Insect Hormones 0 RNA, Messenger 0 Ribonucleoproteins 0 doublesex protein, Drosophila 0 transformer-2 protein IM Alternative Splicing Amino Acid Sequence Animal Base Sequence Conserved Sequence DNA-Binding Proteins genetics Drosophila genetics Evolution, Molecular Female Insect Hormones genetics Introns Male Molecular Sequence Data RNA, Messenger metabolism Ribonucleoproteins genetics isolation & purification Sex Determination (Analysis) Spermatogenesis genetics Support, U.S. Gov't, P.H.S. FBrf0055839 93130760 1362380 1993 02 12 1993 02 12 2000 12 18

0950-1991 116 1 1992 Sep Development of the D. melanogaster caudal segments involves suppression of the ventral regions of A8, A9 and A10. 11-20 Whereas the segmental organization of the thorax and anterior abdomen is morphologically delineated in both the Drosophila larva and adult, segments in the head and caudal regions lack such well-defined boundaries. Consequently, the organization of these regions has been difficult to decipher. In this study, transformations caused by the bithorax-complex homeotic mutants 48, M3, Ultraabdominal-1 (Uab1) and tumorous-head-3 (tuh-3), as well as the patterns of engrailed gene expression have been analyzed to investigate the segmental organization of the caudal segments. A special emphasis was placed on sense organs appearing in abdominal segments 8, 9 and 10 (A8-A10): We find that: (1) transformations in the caudal segments obey parasegmental borders; (2) the sense organs on A8, A9, and A10 are probably homologous to the pits and hairs in anterior A1-A7; (3) except for the larval anal tuft and the anterior side of A8, all structures in larval segments A8, A9 and A10 are dorsal/lateral in origin; and (4) dorsalization of embryonic A8 and A9 cells leaves space ventrally for A10, as it follows the contracting ventral nervous system during the embryological process of germ band contraction. Department of Biology, University of Central Florida, Orlando 32816. Kuhn D T DT Sawyer M M Packert G G Turenchalk G G Mack J A JA Sprey T E TE Gustavson E E Kornberg T B TB eng Journal Article

ENGLAND Development 8701744 IM Abdomen embryology Animal Drosophila melanogaster embryology genetics ultrastructure Embryo, Nonmammalian ultrastructure Gene Expression physiology Genes, Homeobox physiology Microscopy, Electron, Scanning Microscopy, Phase-Contrast Morphogenesis genetics Mutation genetics Sense Organs embryology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0043301 85213614 3923338 1985 07 22 1985 07 22 2000 12 18

0027-5107 150 1-2 1985 Jun-Jul Distribution of MR-induced sex-linked recessive lethal mutations in Drosophila melanogaster. 261-75 In the 'doubling-dose' method currently used in genetic risk evaluation, two principle assumptions are made and these are: (1) there is proportionality between spontaneous and induced mutations and (2) the lesions that lead to spontaneous and induced mutations are essentially similar. The studies reported in this paper were directed at examining the validity of these two assumptions in Drosophila. An analysis was made of the distribution of sex-linked recessive lethals induced by MR, one of the well-studied mutator systems in Drosophila. Appropriate genetic complementation tests with 15 defined X-chromosome duplications showed that MR-induced lethals occurred at many sites along the X-chromosome (in contrast to the known locus specificity of MR-induced visible-mutations); some, but not all these sites at which recessive lethals arose in the MR-system are the same as those known to be hot-spots for X-ray-induced lethals. With in situ hybridization we were able to demonstrate that a majority of MR-induced lethals is associated with a particular mobile DNA sequence, the P-element, i.e. they arose as a result of transposition. The differences between the profiles of MR-induced and X-ray-induced recessive lethals, and the nature of MR-induced and X-ray-induced mutations, thus raise questions about the validity of the assumptions involved in the use of the 'doubling-dose' method. Eeken J C JC Sobels F H FH Hyland V V Schalet A P AP eng Journal Article

NETHERLANDS Mutat Res 0400763 IM Animal Chromosome Mapping DNA Repair Drosophila melanogaster genetics Female Genes, Lethal Genes, Recessive Linkage (Genetics) Mutation radiation effects Support, Non-U.S. Gov't X Chromosome physiology ultrastructure X-Rays FBrf0058044 93246066 8482414 1993 06 03 1993 06 03 2001 11 14

0012-1606 157 1 1993 May Segment-polarity mutations cause stripes of defects along a leg segment in Drosophila. 240-50 Various lines of evidence suggest that "segment-polarity" genes, which participate in segmenting the Drosophila embryo, may also play a role in the development of adult structures. Wilkins and Gubb (1991, Dev. Biol. 145, 1-12) have proposed that these genes specify the angular component of the polar coordinate system for each imaginal disc. If true, then segment-polarity mutations should cause abnormal patterning within well-defined sectors of the discs. To test this prediction, a leg segment was used where abnormalities can be precisely identified. The second-leg basitarsus bears eight rows of mechanosensory bristles, plus five chemosensory bristles between specific rows. Abnormalities were sought in the basitarsi of six different segment-polarity mutants and their 15 pairwise compounds. Consistent with the prediction, sectorial defects were indeed found: (1) deletions of specific rows (or chemosensory bristles) or portions thereof and (2) increased bristle number within (or between) specific rows. Both types of abnormalities were associated with changes in the widths of various parts of the circumference, implying that the alterations in bristle patterning may be mediated by regional perturbations of growth. Department of Biological Sciences, Texas Tech University, Lubbock 79409. Held L I LI Jr eng Journal Article

UNITED STATES Dev Biol 0372762 IM S Animal Chromosome Mapping Drosophila melanogaster anatomy & histology embryology genetics Extremities anatomy & histology Mechanoreceptors ultrastructure Models, Genetic Mutation Phenotype Support, Non-U.S. Gov't Wing anatomy & histology FBrf0043314 85086274 3917555 1985 02 15 1985 02 15 2000 12 18

0028-0836 313 5998 1985 Jan 10-18 Genetic organization of Drosophila bithorax complex. 108-13 The Drosophila bithorax complex is subdivided into three major genes: Ultrabithorax+, abdominal-A+ and Abdominal-B+. Each of these genes plays its principal part in a particular anatomical domain of the body, where it is specifically required to determine the correct segmental pattern. Sánchez-Herrero E E Vernós I I Marco R R Morata G G eng Journal Article

ENGLAND Nature 0410462 IM Animal Drosophila melanogaster genetics growth & development Gene Expression Regulation Genes, Regulator Genetic Complementation Test Morphogenesis Mutation Phenotype Support, Non-U.S. Gov't Thorax FBrf0058046 93273084 8500655 1993 06 28 1993 06 28 2000 12 18

0012-1606 157 2 1993 Jun Delta function is required for bristle organ determination and morphogenesis in Drosophila. 484-96 Analyses of Delta (Dl) temperature-sensitive mutants reveal that reductions in Dl function during metamorphosis of Drosophila melanogaster can lead to multiplication or loss of bristle organs on the adult notum, depending on the developmental interval during which such mutants are pulsed at restrictive temperature. Site-dependent macrochaeta multiplication or loss results from pulses 0-21 hr after puparium formation (APF). Microchaeta multiplication results from pulses 7-30 hr APF, while microchaeta loss results from pulses 24-47 hr APF. Supernumerary bristle organs that develop in Dl mutants consist of the normal complement of trichogen, tormogen, neuron, and thecogen cells, and appear to arise due to the specification of super-numerary bristle first-order precursor (pI) cells within proneural groups in the developing notum. Loss of complete bristle organs in Dl mutants is correlated with the differentiation of all four progeny of the pI cell into neurons. We conclude that Dl function is required for cellular interactions central to the correct specification of pI cells within proneural groups, as well as for morphogenesis of the bristle organ itself. Department of Biology, Indiana University, Bloomington 47405. Parks A L AL Muskavitch M A MA eng GM33291 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 IM Dl Dl<up>6B37</up> Dl<up>9P39</up> Dl<up>RF</up> Animal Drosophila melanogaster genetics growth & development ultrastructure Gene Expression Regulation Metamorphosis, Biological genetics Morphogenesis genetics Mutation Support, U.S. Gov't, P.H.S. Time Factors FBrf0131317 20519455 11063696 2000 11 21 2001 01 04 2002 04 19

0016-6731 156 3 2000 Nov A misexpression screen identifies genes that can modulate RAS1 pathway signaling in Drosophila melanogaster. 1219-30 Differentiation of the R7 photoreceptor cell is dependent on the Sevenless receptor tyrosine kinase, which activates the RAS1/mitogen-activated protein kinase signaling cascade. Kinase suppressor of Ras (KSR) functions genetically downstream of RAS1 in this signal transduction cascade. Expression of dominant-negative KSR (KDN) in the developing eye blocks RAS pathway signaling, prevents R7 cell differentiation, and causes a rough eye phenotype. To identify genes that modulate RAS signaling, we screened for genes that alter RAS1/KSR signaling efficiency when misexpressed. In this screen, we recovered three known genes, Lk6, misshapen, and Akap200. We also identified seven previously undescribed genes; one encodes a novel rel domain member of the NFAT family, and six encode novel proteins. These genes may represent new components of the RAS pathway or components of other signaling pathways that can modulate signaling by RAS. We discuss the utility of gain-of-function screens in identifying new components of signaling pathways in Drosophila. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA. Huang A M AM Rubin G M GM eng HG00750 HG NHGRI Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Ras1 protein EC 2.7.1.- KSR-1 protein kinase EC 2.7.1.- misshapen protein EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 3.6.1.- GTP-Binding Proteins IM Amino Acid Sequence Animal Animals, Genetically Modified Crosses, Genetic Drosophila melanogaster genetics physiology Female GTP-Binding Proteins metabolism Gene Expression Regulation Genes, Insect Genotype Insect Proteins chemistry genetics metabolism Male Mitogen-Activated Protein Kinases metabolism Molecular Sequence Data Photoreceptors, Invertebrate physiology Protein Kinases metabolism Protein-Serine-Threonine Kinases genetics Sequence Alignment Sequence Homology, Amino Acid Signal Transduction genetics Support, U.S. Gov't, P.H.S. FBrf0052602 91094783 2125114 1991 02 14 1991 02 14 2000 12 18

0026-8925 224 3 1990 Dec Transcriptional and translational cis-regulatory sequences of the spermatocyte-specific Drosophila janusB gene are located in the 3' exonic region of the overlapping janusA gene. 450-8 The janus locus of Drosophila melanogaster displays a very unusual organization. It comprises two partially overlapping genes, janA and janB, which are transcribed in the same orientation; the start of transcription of janB, the downstream gene, is located in the 3' exonic region of janA. Both genes are expressed during spermatogenesis. Transcription of janB is restricted to this developmental process, whereas janA is ubiquitously transcribed in both the somatic and germinal tissues of males and females. In order to delimit the cis-acting sequences regulating the transcription of janB, the expression of four chimeric janB-lacZ genes was examined in transgenic lines by Northern blot analysis, in situ hybridization and in situ histochemical staining for beta-galactosidase activity. Results showed that the testis-specific expression of the janB gene is mediated by a short DNA sequence (positions -174 to +107) which is located entirely within the last exon of the upstream janA gene. The tissue specificity of the expression of the janB gene is maintained when most of the janA coding and upstream sequences are deleted. Yet the presence in cis of an active janA gene leads to reduced accumulation of the janB-lacZ hybrid mRNA. This supports the hypothesis that janA transcription interferes with the function of the janB cis-regulatory elements. Our results also demonstrate that the 5' untranslated leader of the janB mRNA contains translational cis-acting elements, which completely block the translation of the janB-lacZ transcripts during the premeiotic stages of sperm development. A janB-lacZ construct was used to examine the sexual phenotype of the germline cells of masculinized XX transformer-2 (tra-2) flies. This has enabled us to confirm at the molecular level previous observations that the germline cells of these flies can enter the spermatogenic pathway of differentiation. Institut J. Monod C.N.R.S. Paris, France. Yanicostas C C Lepesant J A JA eng Journal Article

GERMANY Mol Gen Genet 0125036 0 Recombinant Fusion Proteins IM janA janB tra-2 Animal Blotting, Northern Chromosome Mapping Drosophila melanogaster genetics Exons Gene Expression Regulation Genes, Overlapping Male Nucleic Acid Hybridization Promoter Regions (Genetics) Recombinant Fusion Proteins genetics Regulatory Sequences, Nucleic Acid Spermatocytes physiology Spermatogenesis Support, Non-U.S. Gov't Transcription, Genetic Translation, Genetic FBrf0054119 92146932 1723709 1992 03 13 1992 03 13 2000 12 18

0016-6731 129 4 1991 Dec Structure and transcription of the singed locus of Drosophila melanogaster. 1073-84 Developmental and genetic studies of the singed gene of Drosophila melanogaster indicate that the gene has a role in somatic cells during the formation of adult bristles and hairs, and in the female germline during oogenesis. During metamorphosis a single 3.6-kilobase (kb) RNA is made, and this RNA is also present in adults and early embryos. Early embryos and adult females have additional 3.3- and 3.0-kb RNAs. The RNAs differ only in the length of the 3' untranslated region and a single gene product of 57 kilodaltons is predicted. Analysis of RNA from females lacking ovaries suggests that the 3.3- and 3.0-kb RNAs are made only in ovaries. The absence of the 3.3- and 3.0-kb RNAs in pupae and the time course of their appearance in adult females after eclosion suggests that transcription of singed in the ovary is from middle to late stages of oogenesis. Analysis of RNA in embryos from the reciprocal crosses between wild type and singed-3 showed that all three RNAs are maternally inherited with very little zygotic transcription in embryos. The mutation singed-3 appears to separate the two requirements for singed function as it has an extreme effect upon bristle development, but does not obviously affect oogenesis. In singed-3, there is a deletion at the 5' end of the gene, but the coding region is intact. Transcription in singed-3 is from a cryptic promoter in the upstream flanking sequences which is sufficiently active during oogenesis for fertility, but less active than the wild-type promoter during metamorphosis. The role of the single singed gene product may be in the asymmetric organization and/or movement of cytoplasmic components. Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, England. Paterson J J O'Hare K K eng GENBANK X17548 X17549 X17550 Journal Article

UNITED STATES Genetics 0374636 0 Carrier Proteins 0 Insect Hormones 146808-54-0 fascin 63231-63-0 RNA 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Carrier Proteins genetics DNA Drosophila melanogaster genetics growth & development Female Gene Expression Regulation Insect Hormones genetics Male Metamorphosis, Biological genetics Molecular Sequence Data Oogenesis genetics Ovary cytology metabolism Phenotype RNA metabolism Restriction Mapping Support, Non-U.S. Gov't Transcription, Genetic FBrf0052856 90349599 1696724 1990 09 20 1990 09 20 2000 12 18

0027-8424 87 16 1990 Aug Drosophila homolog of the mammalian jun oncogene is expressed during embryonic development and activates transcription in mammalian cells. 6281-5 By means of low-stringency cross-species hybridization to Southern DNA blots, human c-jun sequences were used to identify a unique Drosophila melanogaster locus (Djun). The predicted DJun protein is highly homologous to members of the mammalian Jun family in both the DNA binding and leucine zipper regions. Djun was mapped by in situ hybridization to position 46E of the second chromosome. It encodes a 1.7-kilobase transcript constitutively expressed at all developmental stages. Functionally, Djun in cooperation with mouse c-fos can trans-activate activator protein 1 DNA binding site when introduced into mammalian cells. Taken together, these data suggest that Djun, much like its mammalian homolog, may activate transcription of genes involved in regulation of cell growth, differentiation, and development. Furthermore, the identification of Djun allows one to exploit the genetics of Drosophila to identify genes in signal transduction pathways involving Djun and thus c-jun. Department of Genetics, Harvard Medical School, Boston, MA 02115. Zhang K K Chaillet J R JR Perkins L A LA Halazonetis T D TD Perrimon N N eng GENBANK M36181 Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA-Binding Proteins 0 Plasmids 0 Proto-Oncogene Proteins c-jun 0 Transcription Factors 63231-63-0 RNA EC 2.7.1.112 Protein-Tyrosine Kinase IM Amino Acid Sequence Animal Base Sequence Blotting, Northern Comparative Study DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Human Molecular Sequence Data Multigene Family Plasmids Protein-Tyrosine Kinase genetics Proto-Oncogene Proteins c-jun Proto-Oncogenes RNA genetics isolation & purification Restriction Mapping Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Transcription Factors genetics FBrf0100672 98108044 9443906 1998 04 09 1998 04 09 2001 11 02

0960-9822 8 3 1998 Jan 29 Photoreceptor development: breaking down the barriers. R90-2 One form of the Tramtrack protein (Ttk88) acts as a general inhibitor of photoreceptor differentiation in developing Drosophila eyes. This inhibition is removed by targeting Ttk88 for degradation, which requires two proteins, Phyl and Sina, previously thought to act in the determination of specific photoreceptor subtypes. Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. Dickson B J BJ eng Journal Article Review Review, Tutorial

ENGLAND Curr Biol 9107782 0 Insect Proteins 0 Nuclear Proteins 0 Repressor Proteins 0 Ubiquitins 0 phyllopod protein 0 seven in absentia protein 0 tramtrack protein EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 3.6.1.- ras Proteins IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase physiology Cell Differentiation Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Insect Proteins genetics physiology Models, Biological Morphogenesis Nuclear Proteins genetics physiology Photoreceptors, Invertebrate embryology Repressor Proteins genetics physiology Transcription, Genetic Ubiquitins metabolism Zinc Fingers ras Proteins physiology 16 FBrf0151899 22296808 12408803 2002 10 31 2002 11 22

1534-5807 3 4 2002 Oct A genomic switch at the transition from cell proliferation to terminal differentiation in the Drosophila eye. 511-21 Organogenesis involves cell proliferation followed by complex determination and differentiation events that are intricately controlled in time and space. The instructions for these different steps are, to a large degree, implicit in the gene expression profiles of the cells that partake in organogenesis. Combining fluorescence-activated cell sorting and SAGE, we analyzed genomic expression patterns in the developing eye of Drosophila melanogaster. Genomic activity changes as cells pass from an uncommitted proliferating progenitor state through determination and differentiation steps toward a specialized cell fate. Analysis of the upstream sequences of genes specifically expressed during the proliferation phase of eye development implicates the transcription factor DREF and its inhibitor dMLF in the control of cell growth in this organ. Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA. henri_jasper@urmc.rochester.edu Jasper Heinrich H Benes Vladimir V Atzberger Ann A Sauer Silvia S Ansorge Wilhelm W Bohmann Dirk D eng Journal Article

United States Dev Cell 101120028 0 DREF protein 0 Drosophila Proteins 0 Transcription Factors 0 myelodysplasia myeloid leukemia factor, Drosophila IM Animal Drosophila Proteins genetics Drosophila melanogaster embryology genetics Eye cytology embryology Gene Expression Profiling Gene Expression Regulation, Developmental Organogenesis genetics Support, Non-U.S. Gov't Transcription Factors genetics FBrf0127377 20253103 10790394 2000 07 11 2000 07 11 2000 12 18

0016-6731 155 1 2000 May The Drosophila melanogaster sex determination gene sisA is required in yolk nuclei for midgut formation. 191-202 During sex determination, the sisterlessA (sisA) gene functions as one of four X:A numerator elements that set the alternative male or female regulatory states of the switch gene Sex-lethal. In somatic cells, sisA functions specifically in sex determination, but its expression pattern also hints at a role in the yolk cell, a syncytial structure believed to provide energy and nutrients to the developing embryo. Previous studies of sisA have been limited by the lack of a null allele, leaving open the possibility that sisA has additional functions. Here we report the isolation and molecular characterization of four new sisA alleles including two null mutations. Our findings highlight key aspects of sisA structure-function and reveal important qualitative differences between the effects of sisA and the other strong X:A numerator element, sisterlessB, on Sex-lethal expression. We use genetic, expression, clonal, and phenotypic analyses to demonstrate that sisA has an essential function in the yolk nuclei of both sexes. In the absence of sisA, endoderm migration and midgut formation are blocked, suggesting that the yolk cell may have a direct role in larval gut development. To our knowledge, this is the first report of a requirement for the yolk nuclei in Drosophila development. Department of Biological Sciences, Columbia University, New York, New York 10027, USA. Walker J J JJ Lee K K KK Desai R N RN Erickson J W JW eng Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Transcription Factors 0 sisterless-a protein IM Alleles Amino Acid Sequence Animal Cell Nucleus DNA-Binding Proteins genetics Digestive System embryology Drosophila melanogaster embryology genetics Endoderm physiology Female Genes, Insect Male Molecular Sequence Data Mutagenesis Phenotype Sex Determination (Genetics) Support, Non-U.S. Gov't Temperature Transcription Factors genetics FBrf0134783 21147302 11252751 2001 03 16 2001 04 05

1471-0056 1 3 2000 Dec Using Drosophila as a model insect. 218-26 The fruit fly Drosophila melanogaster has become such a popular model organism for studying human disease that it is often described as a little person with wings. This view has been strengthened with the sequencing of the Drosophila genome and the discovery that 60% of human disease genes have homologues in the fruit fly. In this review, I discuss the approach of using Drosophila not only as a model for metazoans in general but as a model insect in particular. Specifically, I discuss recent work on the use of Drosophila to study the transmission of disease by insect vectors and to investigate insecticide function and development. Whitehead Institute, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. dschneider@wi.mit.edu Schneider D D eng Journal Article

England Nat Rev Genet 100962779 IM Animal Drosophila melanogaster genetics immunology Human Insect Vectors Models, Animal Pest Control, Biological FBrf0103000 98278915 9611245 1998 07 29 1998 07 29 2002 11 01

0305-1048 26 12 1998 Jun 15 Down regulation of extramacrochaetae mRNA by a Drosophila neural RNA binding protein Rbp9 which is homologous to human Hu proteins. 2989-94 Rbp9 is an RNA binding protein expressed mainly in the central nervous system of adult Drosophilamelanogaster. Rbp9 shares a high degree of sequence similarity with human neural proteins referred to as Hu antigens. Hu antigens bind to U-rich mRNA destabilizing elements with a high affinity and, thus, have been implicated as regulators of mRNA stability. Using in vitro RNA binding assays, we found that Rbp9 binds strongly to poly U sequences. We then employed a Selex system to identify a consensus Rbp9 binding site (UUUXUUUU). Information obtained from the Selex results allowed the detection of two repeats of the Rbp9 consensus binding sequence in the 3' untranslated region of extramacrochaetae mRNA. UV crosslinking experiments demonstrated that Rbp9 interactsspecifically with emc mRNA. The requirement of Rbp9 protein in the down regulation of emc mRNA was confirmed by northern (RNA) analysis, which revealed that the level of emc mRNA increased 10-fold in rbp9 mutant flies. Taken together with the in vitro RNA binding results, the genetic evidence obtained strongly supports the hypothesis that Rbp9 functions as a regulator of RNA stability. Laboratory of Molecular Genetics, Center for Basic Research, Samsung Biomedical Research Institute, Ilwon-dong 50, Kangnam-ku, Seoul 135-230, Korea. Park S J SJ Yang E S ES Kim-Ha J J Kim Y J YJ eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 Cross-Linking Reagents 0 DNA-Binding Proteins 0 HuD antigen 0 Nerve Tissue Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 Rbp9 protein, Drosophila 0 Recombinant Fusion Proteins 0 Sxl protein, Drosophila 0 emc protein 27416-86-0 Poly U IM Animal Base Sequence Binding Sites Cloning, Molecular Consensus Sequence Cross-Linking Reagents DNA-Binding Proteins genetics Drosophila melanogaster genetics Gene Expression Regulation genetics Human Molecular Sequence Data Nerve Tissue Proteins genetics metabolism Poly U metabolism RNA, Messenger genetics metabolism RNA-Binding Proteins genetics metabolism Recombinant Fusion Proteins Repetitive Sequences, Nucleic Acid genetics Ultraviolet Rays FBrf0149134 22038348 12021771 2002 06 03 2002 07 29 2003 03 03

1465-7392 4 6 2002 Jun The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. 445-50 Members of the Inhibitor of Apoptosis Protein (IAP) family block activation of the intrinsic cell death machinery by binding to and neutralizing the activity of pro-apoptotic caspases. In Drosophila melanogaster, the pro-apoptotic proteins Reaper (Rpr), Grim and Hid (head involution defective) all induce cell death by antagonizing the anti-apoptotic activity of Drosophila IAP1 (DIAP1), thereby liberating caspases. Here, we show that in vivo, the RING finger of DIAP1 is essential for the regulation of apoptosis induced by Rpr, Hid and Dronc. Furthermore, we show that the RING finger of DIAP1 promotes the ubiquitination of both itself and of Dronc. Disruption of the DIAP1 RING finger does not inhibit its binding to Rpr, Hid or Dronc, but completely abrogates ubiquitination of Dronc. Our data suggest that IAPs suppress apoptosis by binding to and targeting caspases for ubiquitination. The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK. Wilson Rebecca R Goyal Lakshmi L Ditzel Mark M Zachariou Anna A Baker David A DA Agapite Julie J Steller Hermann H Meier Pascal P eng R01GM60124 GM NIGMS Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Neuropeptides 0 Peptides 0 Ubiquitin 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 reaper peptide, Drosophila EC 3.4.22.- Caspases EC 3.4.22.- DRONC caspase EC 6. Ligases EC 6.3.2.19 E3 ubiquitin ligase IM Animal Apoptosis physiology Caspases metabolism Cells, Cultured Drosophila Drosophila Proteins chemistry genetics metabolism Ligases metabolism Mutagenesis physiology Neuropeptides metabolism Peptides metabolism Photoreceptors, Invertebrate cytology enzymology Protein Binding physiology Protein Structure, Tertiary Retina cytology enzymology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Ubiquitin metabolism FBrf0111352 99417960 10488336 1999 10 12 1999 10 12 2003 06 16

1097-2765 4 2 1999 Aug Smaug, a novel RNA-binding protein that operates a translational switch in Drosophila. 209-18 During Drosophila embryogenesis, a gradient of Nanos protein emanating from the posterior pole organizes abdominal segmentation. This gradient arises from translational regulation of nanos mRNA, which is activated in the specialized cytoplasm at the posterior pole of the embryo and repressed elsewhere. Previously, we have defined cis-acting elements in the mRNA that mediate this translational switch. In this report, we identify a factor named Smaug that binds to these elements and represses translation in the bulk cytoplasm. Smaug interacts gentically and biochemically with Oskar, a key component of the pole plasm for activation of nanos mRNA and specification of the germline precursors. These observations suggest that Smaug operates a translational switch that governs the distribution of Nanos protein. Howard Hughes Medical Institute, Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA. Dahanukar A A Walker J A JA Wharton R P RP eng GENBANK AF159852 Journal Article

UNITED STATES Mol Cell 9802571 0 Insect Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 Recombinant Fusion Proteins 142661-95-8 nanos protein, Drosophila IM Abdomen Amino Acid Sequence Animal Animals, Genetically Modified Base Sequence Binding Sites Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Gene Expression Regulation, Developmental Genomic Library Insect Proteins genetics Molecular Sequence Data Morphogenesis Promoter Regions (Genetics) RNA, Messenger genetics metabolism RNA-Binding Proteins chemistry genetics metabolism Recombinant Fusion Proteins biosynthesis Support, Non-U.S. Gov't Translation, Genetic FBrf0083862 96139863 8569740 1996 03 07 1996 03 07 2000 12 18

0300-8177 149-150 1995 Aug-Sep The cyclic AMP system and Drosophila learning. 271-8 The cyclic AMP (cAMP) system plays a critical role in olfactory learning in the fruit fly, Drosophila melanogaster, as evidenced by the following: [1] The dunce gene encodes a form of cAMP phosphodiesterase (PDE). Flies carrying mutations at this gene show reduced PDE activity, high cAMP levels, and deficits in olfactory learning and memory [2]. The rutabaga gene encodes one type of adenylyl cyclase (AC) similar in properties to the Type I AC characterized from vertebrate brain. This enzyme is activated by G-protein and Ca++ and has been postulated to be a molecular coincidence detector, capable of integrating information from two independent sources such as the conditioned stimulus (CS) and the unconditioned stimulus (US) delivered to animals during Pavlovian conditioning. Rutabaga mutant flies are deficient in AC activity and show behavioral defects similar to those exhibited by dunce mutants [3]. Flies carrying mutations in the gene (DC0) that encodes the catalytic subunit of protein kinase A (PKA), the major mediator of cAMP actions, show alterations in learning performance and a loss in PKA activity. All three genes are expressed preferentially in mushroom bodies, neuroanatomical sites that mediate olfactory learning. Interestingly, the PDE and the catalytic subunit of PKA are found primarily in axonal and dendritic compartments of the mushroom body cells, whereas the AC is found primarily in the axonal compartment. The reason for this differential compartmentalization is unclear, although the hypothetical role of AC as coincidence detector would predict that CS and US stimuli are integrated in the axonal compartment. These observations suggest that cAMP is a dominant second messenger utilized by mushroom body cells to modulate their physiology while the animal is learning and consolidating memory. However, many other types of molecules are likely involved in the physiological alterations that occur in these cells during learning, including cell surface proteins, transcription factors, and synaptic proteins. Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA. Davis R L RL Cherry J J Dauwalder B B Han P L PL Skoulakis E E eng Journal Article

NETHERLANDS Mol Cell Biochem 0364456 0 RNA, Messenger 60-92-4 Cyclic AMP EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases EC 3.1.4.17 3',5'-Cyclic-Nucleotide Phosphodiesterase EC 4.6.1.1 Adenylate Cyclase IM 3',5'-Cyclic-Nucleotide Phosphodiesterase genetics Adenylate Cyclase genetics Animal Cyclic AMP physiology Cyclic AMP-Dependent Protein Kinases genetics Drosophila melanogaster physiology Gene Expression Genes, Structural, Insect Learning physiology Memory physiology RNA, Messenger genetics Signal Transduction Smell physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0145131 21669019 11810242 2002 01 25 2002 02 19 2003 01 03

1617-4615 266 4 2001 Dec A genetic analysis of the cytological region 46C-F containing the Drosophila melanogaster homolog of the jun proto-oncogene. 695-700 The cytogenetic region 46C-F on the right arm of Drosophila chromosome 2, which contains the homolog of the human jun proto-oncogene, has been genetically mapped and characterized. This project led to the identification and characterization of a Jra (jun-related antigen) mutation, which has been described in detail elsewhere. Three mutagens, EMS, DEB and gamma-rays, were used to isolate 126 lethal lines for this interval. Complementation analysis of the 126 lethal lines identified 29 lethal complementation groups in the region; nine of which have now been correlated with known genes or phenotypes. The region has been subdivided into ten intervals using various small deletions, seven intervals in 46C/D and three intervals in 46E/F. Sixteen P-element lines have been mapped to this interval and are allelic to eight of our complementation groups. The remaining unidentified complementation groups have been analyzed for critical phase, which is when the first observable defect arises and/or when death occurs. There are twelve embryonic lethal groups and seven larval lethal groups. Three lines show visible abnormalities in gut and tracheal development prior to death. Department of Biology, Molecular and Cellular Biology Program, Arizona State University, Tempe, AZ 85281-1501, USA. e.goldstein@asu.edu Goldstein E S ES Treadway S L SL Stephenson A E AE Gramstad G D GD Keilty A A Kirsch L L Imperial M M Guest S S Hudson S G SG LaBell A A AA O'Day M M Duncan C C Tallman M M Cattelino A A Lim J J eng Journal Article 2001 10 18

Germany Mol Genet Genomics 101093320 IM Animal Chromosome Mapping Chromosomes ultrastructure Drosophila melanogaster genetics Genes, jun genetics Genetic Complementation Test Mutagenesis, Insertional Sequence Deletion Support, Non-U.S. Gov't FBrf0043249 85162980 3920476 1985 05 08 1985 05 08 2000 12 18

0026-8925 198 2 1985 Polyhomeotic: a gene of Drosophila melanogaster required for correct expression of segmental identity. 213-20 A new locus in Drosophila melanogaster that is required for the correct expression of segmental identity has been discovered. The new locus, termed polyhomeotic (ph), is X-linked and maps cytologically to bands 2D2-3. Homozygous ph flies have homeotic transformations similar to those of known dominant gain of function mutants in the Antennapedia and bithorax complexes (ANT-C, BX-C), and in addition show loss of the humerus. ph interacts with three other similar mutations: Polycomb (Pc), Polycomblike (Pcl), and extra sex comb (esc), and acts as a dominant enhancer of Pc. The expression of ph depends on the ANT-C and BX-C dosage. ph has no embryonic phenotype, but temperature shift studies on ph2 show that the ph+ product is required during embryogenesis and larval development. We propose that ph mutants in some way disrupt the normal expression of the ANT-C and BX-C, and, therefore, that ph+ is needed for maintenance of segmental identity. Dura J M JM Brock H W HW Santamaria P P eng Journal Article

GERMANY, WEST Mol Gen Genet 0125036 IM Animal Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Regulator Genes, Structural Morphogenesis Phenotype Support, Non-U.S. Gov't Temperature FBrf0057927 93314432 8325168 1993 08 06 1993 08 06 2000 12 18

0009-5915 102 5 1993 May Chromosomal homologies between Drosophila lebanonensis and D. melanogaster determined by in situ hybridization. 361-8 Twelve biotin-labelled recombinant DNA probes were hybridized to polytene chromosomes of Drosophila melanogaster and D. lebanonensis. Probes were chosen in order to cover the whole chromosomal complement. Six probes correspond to known genes from D. melanogaster (RpII215, H3-H4, MHC, hsp28/23, hsp83, hsp70), four probes are clones isolated from a D. subobscura library (Xdh, lambda DsubS3, lambdaDsubG3, lambdaDsubG4) and the remaining two probes correspond to the Adh gene of D. lebanonensis and to one sequence (262), not yet characterized, from the same species. The chromosomal homologies obtained from the in situ hybridization results allow us to determine that Muller's C and D chromosomal elements are fused in the karyotype of D. lebanonensis and constitute the large metacentric chromosome. Single pericentric inversions in the E and B elements have generated the medium and small metacentric chromosomes, respectively. No great changes are detected in Muller's A element, which remains acrocentric. The changes detected in the karyotypic evolution of D. lebanonensis are frequently observed in Drosophila evolution, as deduced from chromosomal homologies of several Drosophila species. The results are also consistent with Muller's proposal that chromosomal elements have been conserved during the evolution of Drosophila. Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain. Papaceit M M Juan E E eng Journal Article

GERMANY Chromosoma 2985138R 0 DNA Probes EC 1.1.1.1 Alcohol Dehydrogenase IM Alcohol Dehydrogenase genetics Animal Chromosome Banding Chromosomes DNA Probes Drosophila genetics Drosophila melanogaster genetics In Situ Hybridization Karyotyping Salivary Glands cytology Species Specificity FBrf0108091 99182490 10082569 1999 04 20 1999 04 20 2002 11 01

0270-7306 19 4 1999 Apr An N-terminal truncation uncouples the sex-transforming and dosage compensation functions of sex-lethal. 3018-28 In Drosophila melanogaster, Sex-lethal (Sxl) controls autoregulation and sexual differentiation by alternative splicing but regulates dosage compensation by translational repression. To elucidate how Sxl functions in splicing and translational regulation, we have ectopically expressed a full-length Sxl protein (Sx.FL) and a protein lacking the N-terminal 40 amino acids (Sx-N). The Sx.FL protein recapitulates the activity of Sxl gain-of-function mutations, as it is both sex transforming and lethal in males. In contrast, the Sx-N protein unlinks the sex-transforming and male-lethal effects of Sxl. The Sx-N proteins are compromised in splicing functions required for sexual differentiation, displaying only partial autoregulatory activity and almost no sex-transforming activity. On the other hand, the Sx-N protein does retain substantial dosage compensation function and kills males almost as effectively as the Sx.FL protein. In the course of our analysis of the Sx.FL and Sx-N transgenes, we have also uncovered a novel, negative autoregulatory activity, in which Sxl proteins bind to the 3' untranslated region of Sxl mRNAs and decrease Sxl protein expression. This negative autoregulatory activity may be a homeostasis mechanism. Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. jly@phoenix.princeton.edu Yanowitz J L JL Deshpande G G Calhoun G G Schedl P D PD eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 3' Untranslated Regions 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM 3' Untranslated Regions Alternative Splicing Animal Comparative Study Dosage Compensation (Genetics) Drosophila genetics Female Gene Expression Regulation Male Mutation RNA-Binding Proteins genetics Sequence Deletion Sex Differentiation genetics Transgenes Translation, Genetic FBrf0092739 97184492 9032294 1997 03 14 1997 03 14 2002 11 01

0270-7306 17 3 1997 Mar The Sex-lethal early splicing pattern uses a default mechanism dependent on the alternative 5' splice sites. 1674-81 The Sex-lethal (Sxl) early transcripts have a unique 5' exon and a splicing pattern that differs from that of the late transcripts. While the late transcripts are regulated sex specifically by control of exon 3 inclusion, the early transcripts are not. While the late transcripts include exon 3 by default, the early transcripts skip exon 3. Splicing patterns of a reporter gene that mimics the early transcript, and its variants, were analyzed in Drosophila transformants and tissue culture cells. The results demonstrate that the early, in contrast to the late, splicing pattern is not regulated by stage-specific or sex-specific trans-acting factors, and so the pattern appears to arise from some type of intrinsic splice site preference or compatibility. Inclusion or exclusion of exon 3 is determined by the identity of the upstream 5' splice site region as late or early. The important region of the early exon lies within 233 nucleotides of the immediately adjacent intron. Department of Biological Sciences, University of Southern California, Los Angeles 90089-1340, USA. Zhu C C Urano J J Bell L R LR eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 RNA Precursors 0 RNA, Messenger 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Alternative Splicing genetics Animal Base Sequence Drosophila melanogaster genetics Exons genetics Female Genes, Reporter genetics Introns genetics Male Molecular Sequence Data RNA Precursors genetics RNA Splicing genetics RNA, Messenger genetics RNA-Binding Proteins genetics Sequence Deletion Support, Non-U.S. Gov't FBrf0049805 90108691 2514120 1990 02 22 1990 02 22 2000 12 18

0890-9369 3 9 1989 Sep cappuccino and spire: two unique maternal-effect loci required for both the anteroposterior and dorsoventral patterns of the Drosophila embryo. 1437-52 cappuccino and spire are unique Drosophila maternal-effect loci that participate in pattern formation in both the anteroposterior and dorsoventral axes of the early embryo. Mutant females produce embryos lacking pole cells, polar granules, and normal abdominal segmentation. They share these defects with the posterior group of maternal-effect genes. Although embryos are defective in abdominal segmentation, in double mutant combinations with Bicaudal D, abdominal segments can be formed in the anterior half of the egg. This indicates that embryos produced by mutant females contain the 'posterior determinant' required for abdominal segmentation (Nüsslein-Volhard et al. 1987) and suggests that the wild-type gene products are not required for production of the posterior determinant but, rather, for its localization or stabilization. The vasa protein, a component of polar granules, is not localized at the posterior pole of mutant egg chambers or embryos, providing additional support for the hypothesis that localization to or stabilization of substances at the posterior pole of the egg chamber is defective in mutant females. Females mutant for the strongest alleles also produce dorsalized embryos. Phenotypic analysis reveals that these dorsalized embryos also have abdominal segmentation defects. The mutant phenotypes can be ordered in a series of increasing severity. Pole cell formation is most sensitive to loss of functional gene products, followed by abdominal segmentation, whereas normal dorsoventral patterning is the least sensitive to loss of functional gene products. In addition, mutant females contain egg chambers that appear to be dorsalized, resulting in the production of eggs with dorsalized eggshells. Germ-line mosaics indicate that cappuccino and spire are required in the oocyte-nurse cell complex. This suggests that the eggshell phenotype results from altered pattern in the underlying germ cell. Also, we defined the epistatic relationships between several early patterning loci, on the basis of an analysis of the eggs and embryos produced by females doubly mutant for cappuccino or spire and other loci that affect the pattern of both the egg and the embryo. On the basis of our current knowledge of the genes involved in this process, we formulated a working model for the early steps in dorsoventral patterning. Department of Biology, Princeton University, New Jersey 08544. Manseau L J LJ Schüpbach T T eng 5 F32 GM-11404-02 BI-7 GM NIGMS GM-40558-01 GM NIGMS Journal Article

UNITED STATES Genes Dev 8711660 IM Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian anatomy & histology Female Genes Morphogenesis Mutation Oogenesis Ovum ultrastructure Phenotype Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0087684 96202461 8625828 1996 06 21 1996 06 21 2000 12 18

0950-1991 122 5 1996 May Development of the Drosophila tracheal system occurs by a series of morphologically distinct but genetically coupled branching events. 1395-407 The tracheal (respiratory) system of Drosophila melanogaster is a branched network of epithelial tubes that ramifies throughout the body and transports oxygen to the tissues. It forms by a series of sequential branching events in each hemisegment from T2 to A8. Here we present a cellular and initial genetic analysis of the branching process. We show that although branching is sequential it is not iterative. The three levels of branching that we distinguish involve different cellular mechanisms of tube formation. Primary branches are multicellular tubes that arise by cell migration and intercalation; secondary branches are unicellular tubes formed by individual tracheal cells; terminal branches are subcellular tubes formed within long cytoplasmic extensions. Each level of branching is accompanied by expression of a different set of enhancer trap markers. These sets of markers are sequentially activated in progressively restricted domains and ultimately individual tracheal cells that are actively forming new branches. A clonal analysis demonstrates that branching fates are not assigned to tracheal cells until after cell division ceases and branching begins. We further show that the breathless FGF receptor, a tracheal gene required for primary branching, is also required to activate expression of markers involved in secondary branching and that the pointed ETS-domain transcription factor is required for secondary branching and also to activate expression of terminal branch markers. The combined morphological, marker expression and genetic data support a model in which successive branching events are mechanistically and genetically distinct but coupled through the action of a tracheal gene regulatory hierarchy. Department of Biochemistry, Stanford University, CA 94305, USA. Samakovlis C C Hacohen N N Manning G G Sutherland D C DC Guillemin K K Krasnow M A MA eng Journal Article

ENGLAND Development 8701744 0 Antigens, Differentiation IM Animal Antigens, Differentiation Cell Count Cell Lineage Cell Movement Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Morphogenesis Respiratory System cytology embryology FBrf0109147 99282503 10353905 1999 07 08 1999 07 08 2000 12 18

0016-6731 152 2 1999 Jun Genetic analysis of the bone morphogenetic protein-related gene, gbb, identifies multiple requirements during Drosophila development. 629-40 We have isolated mutations in the Drosophila melanogaster gene glass bottom boat (gbb), which encodes a TGF-beta signaling molecule (formerly referred to as 60A) with highest sequence similarity to members of the bone morphogenetic protein (BMP) subgroup including vertebrate BMPs 5-8. Genetic analysis of both null and hypomorphic gbb alleles indicates that the gene is required in many developmental processes, including embryonic midgut morphogenesis, patterning of the larval cuticle, fat body morphology, and development and patterning of the imaginal discs. In the embryonic midgut, we show that gbb is required for the formation of the anterior constriction and for maintenance of the homeotic gene Antennapedia in the visceral mesoderm. In addition, we show a requirement for gbb in the anterior and posterior cells of the underlying endoderm and in the formation and extension of the gastric caecae. gbb is required in all the imaginal discs for proper disc growth and for specification of veins in the wing and of macrochaete in the notum. Significantly, some of these tissues have been shown to also require the Drosophila BMP2/4 homolog decapentaplegic (dpp), while others do not. These results indicate that signaling by both gbb and dpp may contribute to the development of some tissues, while in others, gbb may signal independently of dpp. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA. kristi_wharton@brown.edu Wharton K A KA Cook J M JM Torres-Schumann S S de Castro K K Borod E E Phillips D A DA eng Journal Article

UNITED STATES Genetics 0374636 0 60A protein 0 Bone Morphogenetic Proteins 0 Transforming Growth Factor beta 9007-49-2 DNA IM Alleles Animal Bone Morphogenetic Proteins genetics Chromosome Mapping Chromosomes genetics DNA genetics Drosophila embryology genetics growth & development Embryo, Nonmammalian metabolism Female Gastrointestinal System embryology metabolism Gene Expression Regulation, Developmental Genes, Lethal Genetic Complementation Test Genotype Larva genetics Male Malpighian Tubules embryology metabolism Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transforming Growth Factor beta genetics Wing growth & development metabolism FBrf0039034 84083679 6418476 1984 02 24 1984 02 24 2000 12 18

0009-5915 88 4 1983 Cytogenetic analysis of variegation suppressors and a dominant temperature-sensitive lethal in region 23-26 of chromosome 2L in Drosophila melanogaster. 277-85 Three suppressor loci for position-effect variegation, one dominant temperature-sensitive (DTS), three Minute genes, and two recessive visible mutants (ed, tkv) have been cytogenetically localized by using duplications and deficiencies in regions 23-25 of chromosome arm 2L of Drosophila melanogaster. Two of the suppressor loci studied proved to represent haplo-abnormal genes localized in regions 23A6-23F6 and 24E2-25A1, respectively. The third one is a strong triplo-abnormal suppressor mapping in 25F4-26B9 which affects white variegation in wm4h when present in three doses. The l(2)2DTS mutation, which belongs to a group of noncomplementing dominant temperature-sensitive mutations, is localized in the 25A4-B1 region. Furthermore, two Minute genes have been localized in region 24 that are included in Df(2L)M11 and can be separated employing translocation (Y;2)P8 (24E2-4): M(2)LS2 in 24D3-4-24E2-4, and M(2)z in 24E4-5-24F5-7. A third Minute gene (M(2)S1) is localized in 25C3-8-25C9-D1. The usefulness of the isolated chromosomal rearrangements for further genetic studies of region 23-26 is discussed. Reuter G G Szidonya J J eng Journal Article

GERMANY, WEST Chromosoma 2985138R IM Animal Chromosome Mapping Chromosomes ultrastructure Drosophila melanogaster genetics Genes, Dominant Genes, Lethal Genetic Complementation Test Support, Non-U.S. Gov't Suppression, Genetic FBrf0108441 99246283 10228172 1999 06 28 1999 06 28 2000 12 18

0261-4189 18 9 1999 May 4 Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster. 2610-20 Maternally synthesized RNAs program early embryonic development in many animals. These RNAs are degraded rapidly by the midblastula transition (MBT), allowing genetic control of development to pass to zygotically synthesized transcripts. Here we show that in the early embryo of Drosophila melanogaster, there are two independent RNA degradation pathways, either of which is sufficient for transcript elimination. However, only the concerted action of both pathways leads to elimination of transcripts with the correct timing, at the MBT. The first pathway is maternally encoded, is targeted to specific classes of mRNAs through cis-acting elements in the 3'-untranslated region and is conserved in Xenopus laevis. The second pathway is activated 2 h after fertilization and functions together with the maternal pathway to ensure that transcripts are degraded by the MBT. Program in Developmental Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Bashirullah A A Halsell S R SR Cooperstock R L RL Kloc M M Karaiskakis A A Fisher W W WW Fu W W Hamilton J K JK Etkin L D LD Lipshitz H D HD eng GM50221 GM NIGMS T32GM07616 GM NIGMS Journal Article

ENGLAND EMBO J 8208664 0 3' Untranslated Regions 0 Heat-Shock Proteins 0 RNA, Messenger 0 heat-shock protein 83 IM 3' Untranslated Regions Animal Base Sequence Blastocyst metabolism Drosophila melanogaster embryology metabolism Evolution, Molecular Female Heat-Shock Proteins biosynthesis genetics Molecular Sequence Data Mutation Ovum metabolism RNA, Messenger metabolism Sex Factors Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Time Factors Xenopus Zygote metabolism FBrf0134799 21135093 11242113 2001 03 12 2001 04 12

1061-4036 27 3 2001 Mar Chromatin profiling using targeted DNA adenine methyltransferase. 304-8 Chromatin is the highly complex structure consisting of DNA and hundreds of associated proteins. Most chromatin proteins exert their regulatory and structural functions by binding to specific chromosomal loci. Knowledge of the identity of these in vivo target loci is essential for the understanding of the functions and mechanisms of action of chromatin proteins. We report here large-scale mapping of in vivo binding sites of chromatin proteins, using a novel approach based on a combination of targeted DNA methylation and microarray technology. We show that three distinct chromatin proteins in Drosophila melanogaster cells each associate with specific sets of genes. HP1 binds predominantly to pericentric genes and transposable elements. GAGA factor associates with euchromatic genes that are enriched in (GA)n motifs. A Drosophila homolog of Saccharomyces cerevisiae Sir2p is associated with several active genes and is excluded from heterochromatin. High-resolution, genome-wide maps of target loci of chromatin proteins ('chromatin profiles') provide new insights into chromatin structure and gene regulation. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. steesel@chem.uva.nl van Steensel B B Delrow J J Henikoff S S eng Journal Article

United States Nat Genet 9216904 0 Chromatin EC 2.1.1.- Dam methyltransferase EC 2.1.1.72 Site-Specific DNA-Methyltransferase (Adenine-Specific) IM Nat Genet. 2001 Mar;27(3):240-1 11242099 Animal Binding Sites genetics Cell Line Chromatin genetics metabolism DNA Methylation Drosophila melanogaster genetics metabolism Gene Expression Profiling methods Oligonucleotide Array Sequence Analysis Site-Specific DNA-Methyltransferase (Adenine-Specific) FBrf0077515 95025969 7939712 1994 11 21 1994 11 21 2000 12 18

0036-8075 266 5185 1994 Oct 28 Developmental evolution: insights from studies of insect segmentation. 581-90 Rapid advances have been made in the understanding of the genetic basis of development and pattern formation in a variety of model systems. By examining the extent to which these developmental systems are conserved or altered between different organisms, insight can be gained into the evolutionary events that have generated the diversity of organisms around us. The molecular and genetic basis of early pattern formation in Drosophila melanogaster has been particularly well studied, and comparisons to other insects have revealed conservation of some aspects of development, as well as differences that may explain variations in early patterning events. Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210-3399. Patel N H NH eng Journal Article Review Review, Tutorial

UNITED STATES Science 0404511 IM Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian growth & development Evolution Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Insects embryology genetics Morphogenesis Phylogeny Signal Transduction 57 FBrf0048250 88284312 2840332 1988 08 26 1988 08 26 2000 12 18

0016-6731 119 1 1988 May Molecular analysis of an unstable P element insertion at the singed locus of Drosophila melanogaster: evidence for intracistronic transposition of a P element. 85-94 In a companion study, a number of P element insertions into the singed locus were characterized. Here is reported a detailed analysis of the structure and mutability of another P element insertion at sn, known as sncm. Under conditions which mobilize P elements, sncm mutates at high frequency to both wild-type (sn+) and to a much more extreme allele (snext). Wild-type revertants appear to represent precise or nearly precise excisions of the P element. Certainly two, and most likely all five, of the snext alleles studied result from the insertion of a duplicate copy of this P element into a nearby site in an inverted orientation. We propose a model in which both the sn+ and snext mutational events can be explained by excision of the P element from one chromatid followed by reintegration into the sister chromatid at a nearby site (intracistronic transposition). Finally, it is shown that the snext alleles are themselves unstable and the structure of a resulting chromosome aberration is examined. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461. Hawley R S RS Steuber R A RA Marcus C H CH Sohn R R Baronas D M DM Cameron M L ML Zitron A E AE Chase J W JW eng CA13330 CA NCI GM 11301 GM NIGMS GM 32870 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 9007-49-2 DNA IM Alleles Animal Base Sequence Chromosome Mapping DNA isolation & purification DNA Transposable Elements Drosophila melanogaster genetics Genes, Structural Immunochemistry Microscopy, Electron, Scanning Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0151698 22224856 12239569 2002 09 19 2002 10 21

0028-0836 419 6904 2002 Sep 19 Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. 304-8 Developmental patterning relies on morphogen gradients, which generally involve feedback loops to buffer against perturbations caused by fluctuations in gene dosage and expression. Although many gene components involved in such feedback loops have been identified, how they work together to generate a robust pattern remains unclear. Here we study the network of extracellular proteins that patterns the dorsal region of the Drosophila embryo by establishing a graded activation of the bone morphogenic protein (BMP) pathway. We find that the BMP activation gradient itself is robust to changes in gene dosage. Computational search for networks that support robustness shows that transport of the BMP class ligands (Scw and Dpp) into the dorsal midline by the BMP inhibitor Sog is the key event in this patterning process. The mechanism underlying robustness relies on the ability to store an excess of signalling molecules in a restricted spatial domain where Sog is largely absent. It requires extensive diffusion of the BMP-Sog complexes, coupled with restricted diffusion of the free ligands. We show experimentally that Dpp is widely diffusible in the presence of Sog but tightly localized in its absence, thus validating a central prediction of our theoretical study. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. Eldar Avigdor A Dorfman Ruslan R Weiss Daniel D Ashe Hilary H Shilo Ben-Zion BZ Barkai Naama N eng Journal Article

England Nature 0410462 0 Bone Morphogenetic Proteins 0 Drosophila Proteins 0 Ligands 0 Macromolecular Systems 0 SCW protein, Drosophila 0 TSG protein, Drosophila 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 0 sog protein, Drosophila 144714-21-6 tld protein, Drosophila IM Nature. 2002 Sep 19;419(6904):261-2 12239551 Animal Body Patterning Bone Morphogenetic Proteins antagonists & inhibitors genetics metabolism Diffusion Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics metabolism Embryo, Nonmammalian embryology metabolism Gene Dosage Genotype Ligands Macromolecular Systems Models, Biological Phenotype Support, Non-U.S. Gov't Transforming Growth Factor beta genetics metabolism FBrf0107756 99231493 10217141 1999 06 10 1999 06 10 2002 11 01

0028-0836 398 6728 1999 Apr 15 Structural basis for recognition of the tra mRNA precursor by the Sex-lethal protein. 579-85 The Sex-lethal (Sxl) protein of Drosophila melanogaster regulates alternative splicing of the transformer (tra) messenger RNA precursor by binding to the tra polypyrimidine tract during the sex-determination process. The crystal structure has now been determined at 2.6 A resolution of the complex formed between two tandemly arranged RNA-binding domains of the Sxl protein and a 12-nucleotide, single-stranded RNA derived from the tra polypyrimidine tract. The two RNA-binding domains have their beta-sheet platforms facing each other to form a V-shaped cleft. The RNA is characteristically extended and bound in this cleft, where the UGUUUUUUU sequence is specifically recognized by the protein. This structure offers the first insight, to our knowledge, into how a protein binds specifically to a cognate RNA without any intramolecular base-pairing. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan. Handa N N Nureki O O Kurimoto K K Kim I I Sakamoto H H Shimura Y Y Muto Y Y Yokoyama S S eng PDB 1B7F Journal Article

ENGLAND Nature 0410462 0 Insect Hormones 0 Macromolecular Systems 0 Nuclear Proteins 0 Pyrimidines 0 RNA Precursors 0 RNA, Messenger 0 RNA-Binding Proteins 0 Recombinant Proteins 0 Sxl protein, Drosophila 0 transformer protein, Drosophila IM Amino Acid Sequence Animal Base Pairing Crystallography, X-Ray Drosophila melanogaster Escherichia coli Insect Hormones chemistry metabolism Macromolecular Systems Models, Molecular Molecular Sequence Data Nuclear Proteins chemistry genetics Nucleic Acid Conformation Protein Binding Protein Conformation Protein Structure, Secondary Pyrimidines chemistry RNA Precursors chemistry metabolism RNA, Messenger genetics RNA-Binding Proteins chemistry metabolism Recombinant Proteins chemistry genetics metabolism Sequence Alignment Support, Non-U.S. Gov't FBrf0049898 90060708 2511071 1990 01 05 1990 01 05 2000 12 18

0016-6731 123 2 1989 Oct Gross genetic dissection and interaction of the chromosomal region 95E;96F of Drosophila melanogaster. 371-7 Making use of deficiencies, inversions and translocations, we have genetically dissected the region 95E to 96F of Drosophila melanogaster. We localized cytologically the loci abnormal spindle (asp: 3-85.2: 96A20-25;96B1-10) and M(3)96C2 (96C1;96C5). We have also found several new phenotypes associated with lesions in the 95E to 97B region: (1) Minute(3)96A (M(3)96A) is a haplo-insufficient phenotype of thin and short bristles presented by individuals deficient for the region 95E6-8;96A1-5. (2) abdominal-one reduced (aor) shows two different phenotypes associated with the distal breakpoint of In(3R)Ubx7L (89E;96A1-7). One is the increase of the Ubx phenotype, but its effect requires the presence of lesions in Ubx. The other phenotype is a drastic reduction or disappearance of the first abdominal segment. Both phenotypes might be due to lesions in the same gene. (3) metaphase arrest (mar) is associated with the breakpoint of the T(Y;3)B197 (96B1-10) and produces a phenotype typical of mitotic mutants with arrest of the cell cycle during prometaphase or metaphase. There is another region localized in 97B which interacts with asp: in a background homozygous for asp, three doses of this region enhance the asp phenotype. Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma de Madrid, Spain. González C C Molina I I Casal J J Ripoll P P eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Banding Chromosome Mapping Chromosomes Drosophila melanogaster genetics Female Genes Genotype Inversion (Genetics) Male Metaphase Mitotic Spindle Apparatus metabolism Multigene Family Mutation Phenotype Recombination, Genetic Support, Non-U.S. Gov't Translocation (Genetics) FBrf0054872 91319397 1713660 1991 09 05 1991 09 05 2000 12 18

0950-9232 6 7 1991 Jul D-elg, a member of the Drosophila ets gene family: sequence, expression and evolutionary comparison. 1175-83 We have cloned a cDNA from the Drosophila elg gene, a new member of the ets family of genes. The D-elg gene is located at 97D on chromosome 3R and is expressed as a 2.0kb RNA in the embryos, pupae and adults, with no detectable expression in third instar larvae. D-elg expression is observed in all cells of early stage embryos, prior to transcriptional activation of the zygotic genome, and is maintained throughout embryogenesis with no regional localization. The cDNA encodes a predicted protein of 15.4kD that has an 86 amino acid sequence with 72% similarity to the carboxy terminal region of the Drosophila ets-2 gene. Comparison with all known ets genes allows us to define a minimal region required for assignment to the ets gene family. Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201. Pribyl L J LJ Watson D K DK Schulz R A RA Papas T S TS eng GENBANK S74824 S74828 S74831 S74923 S74924 S74925 S74926 X58481 X59291 X59292 Journal Article

ENGLAND Oncogene 8711562 0 Proto-Oncogene Proteins 0 proto-oncogene protein ets 146312-44-9 D-elg protein 63231-63-0 RNA 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping DNA genetics isolation & purification Drosophila melanogaster embryology genetics growth & development Gene Expression Molecular Sequence Data Nucleic Acid Hybridization Proto-Oncogene Proteins chemistry genetics Pupa metabolism RNA metabolism Support, U.S. Gov't, Non-P.H.S. FBrf0049219 89334794 2502978 1989 08 30 1989 08 30 2000 12 18

0001-8244 19 3 1989 May Courtship behavior of Drosophila genetically or surgically deprived of basiconic sensilla. 371-85 The lack of basiconic antennal sensilla in the mutant lozenge was used to assess the role of these olfactory receptors in the courtship behavior of Drosophila melanogaster. Under normal light conditions, lozenge males courted virgin females much less than wild-type males did. However, when visual courtship stimuli were eliminated by studying behavior under dim red light, the two kinds of males courted individual wild-type virgin females with the same intensity, and the latency to copulation was similar. Also, no difference in courtship vigor was observed if the two kinds of males were paired in red light with a mated female. These data suggest that antennal basiconic sensilla are important for neither the perception of the attraction pheromone(s) of virgin females nor the inhibitory pheromone(s) of mated females. Similar assays with males deprived of maxillary palps make it unlikely that the basiconic-like sensilla on these appendages are needed to perceive the attraction pheromones. However, the unexpectedly high courtship activity of palp-deprived males toward mated females suggests that basiconic-like maxillary sensilla may be receptors of inhibitory female compounds. Stocker R F RF Gendre N N eng Journal Article

UNITED STATES Behav Genet 0251711 0 Sex Attractants IM Animal Chemoreceptors physiology Drosophila melanogaster genetics Female Male Mutation Phenotype Sensory Deprivation physiology Sex Attractants physiology Sex Behavior, Animal physiology Smell physiology Support, Non-U.S. Gov't FBrf0084100 96100378 8555109 1996 02 27 1996 02 27 2000 12 18

0925-4773 53 1 1995 Sep Analysis of the genes involved in organizing the tail segments of the Drosophila melanogaster embryo. 3-13 The metameric organization of the Drosophila melanogaster tail is obscured by developmental events that partially suppress or fuse some of its regions. To better define the developmental origins and segmental identities in the tail of the Drosophila embryo, we documented expression patterns and mutant phenotypes of several genes that play important roles in its morphogenesis. We documented the domains of engrailed (en), Abdominal-B (Abd-B) and caudal (cad) expression in the tail region. The staining pattern of cut (ct) was used to correlate the embryonic sense organs with their respective positions on the larval cuticle. The en patterns in different Bithorax-Complex (BX-C) Abd-B morphogenetic (m) and regulatory (r) mutants demonstrated that Abd-B functions to, among other things, suppress embryonic ventral epidermal structures on the posterior side of A8 to A9. Ventral epidermal structures were not added back into the en pattern in r- or BX-C- mutants, indicating that although the BX-C functions extend through A10, other non-BX-C genes must be required for development of this segment. Department of Biology, University of Central Florida, Orlando 32816, USA. Kuhn D T DT Turenchalk G G Mack J A JA Packert G G Kornberg T B TB eng Journal Article

IRELAND Mech Dev 9101218 0 Molecular Probes IM Animal Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental physiology Genes, Homeobox Genes, Insect Molecular Probes Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Tail embryology FBrf0049404 92096481 2519613 1992 02 06 1992 02 06 2000 12 18

1044-2030 1 1 1989 Nov Regulation of HSP70 synthesis by messenger RNA degradation. 135-49 When Drosophila cells are heat shocked, hsp70 messenger RNA (mRNA) is stable and is translated at high efficiencies. During recovery from heat shock, hsp70 synthesis is repressed and its messenger RNA (mRNA) is degraded in a highly regulated fashion. Dramatic differences in the timing of repression and degradation are observed after heat treatments of different severities. The 3' untranslated region (UTR) of the hsp70 mRNA was sufficient to transfer this regulated degradation to heterologous mRNAs. Altering the translational efficiency of the message or changing its natural translation-termination site did not alter its pattern of regulation, although in some cases it changed the absolute rate of degradation. We have previously shown that hsp70 mRNA is very unstable when it is expressed at normal growth temperatures (from a metallothionein promoter). We report here that the 3' untranslated region of the hsp70 mRNA is responsible for this instability as well. We postulate that a mechanism for degrading hsp70 mRNA pre-exists in Drosophila cells, that it is inactivated by heat shock and that it is the reactivation of this mechanism that is responsible for hsp70 repression during recovery. This degradation system may be the same as that used by other unstable mRNAs. Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637. Petersen R B RB Lindquist S S eng F32 GM11794 GM NIGMS Journal Article

UNITED STATES Cell Regul 9005331 0 Heat-Shock Proteins 0 Plasmids 0 RNA, Messenger IM Animal Cells, Cultured Chromosome Mapping Drosophila melanogaster Gene Expression Heat-Shock Proteins biosynthesis genetics Plasmids RNA, Messenger genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Translation, Genetic FBrf0152273 22329428 12441051 2002 11 20 2002 12 19 2003 05 30

0896-6273 36 4 2002 Nov 14 A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding. 611-22 We demonstrate that Drosophila capulet (capt), a homolog of the adenylyl cyclase-associated protein that binds and regulates actin in yeast, associates with Abl in Drosophila cells, suggesting a functional relationship in vivo. We find a robust and specific genetic interaction between capt and Abl at the midline choice point where the growth cone repellent Slit functions to restrict axon crossing. Genetic interactions between capt and slit support a model where Capt and Abl collaborate as part of the repellent response. Further support for this model is provided by genetic interactions that both capt and Abl display with multiple members of the Roundabout receptor family. These studies identify Capulet as part of an emerging pathway linking guidance signals to regulation of cytoskeletal dynamics and suggest that the Abl pathway mediates signals downstream of multiple Roundabout receptors. Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Wills Zachary Z Emerson Mark M Rusch Jannette J Bikoff Jay J Baum Buzz B Perrimon Norbert N Van Vactor David D eng NS35909 NS NINDS Journal Article

United States Neuron 8809320 0 Cell Cycle Proteins 0 Nerve Tissue Proteins 0 Receptors, Immunologic 0 Slit1 protein 0 adenyl cyclase-associated protein 0 robo2 protein 0 robo3 protein EC 2.7.1.- ARG tyrosine kinase EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal Cell Communication genetics Cell Cycle Proteins genetics metabolism Cell Differentiation genetics Cells, Cultured Chemotaxis genetics Drosophila melanogaster embryology genetics ultrastructure Female Gene Expression Regulation, Developmental genetics Growth Cones metabolism ultrastructure Immunohistochemistry Male Microscopy, Electron, Scanning Mutation genetics Nerve Tissue Proteins genetics metabolism Nervous System embryology metabolism ultrastructure Protein-Tyrosine Kinase genetics metabolism Receptors, Immunologic genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0056157 92331917 1628819 1992 08 18 1992 08 18 2002 11 01

0016-6723 59 2 1992 Apr Mapping and characterization of a 'speciation gene' in Drosophila. 73-80 Almost nothing is known about the identity of the genes causing reproductive isolation between species. As a first step towards molecular isolation of a 'speciation gene', I mapped and partly characterized a gene causing hybrid male sterility in Drosophila. This analysis shows that sterility of D. melanogaster males who carry the 'dot' fourth chromosome from D. simulans is due entirely to a very small region of the D. simulans chromosome (including only about 5 salivary gland bands or approximately 250 kb of DNA). Thus the hybrid sterility effect of the D. simulans fourth chromosome is almost surely due to a single gene of very large effect (here named hms, hybrid male sterile). Hms is zygotically acting, and the D. simulans allele of hms is completely recessive. Furthermore, complementation tests suggest that hms is not an allele of any known locus in D. melanogaster. Center for Population Biology, University of California, Davis 95616. Orr H A HA eng GM 38462 GM NIGMS Journal Article

ENGLAND Genet Res 0370741 IM hms Alleles Animal Chromosome Mapping Chromosomes Drosophila genetics Drosophila melanogaster genetics Evolution Fertility genetics Genes, Recessive Homozygote Hybridization, Genetic genetics Infertility, Male genetics Male Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0068755 94186043 8138156 1994 04 25 1994 04 25 2000 12 18

0016-6731 136 1 1994 Jan Modifications of the notch function by Abruptex mutations in Drosophila melanogaster. 183-94 The function of the Notch gene is required in cell interactions defining alternative cell fates in several developmental processes. The Notch gene encodes a transmembrane protein with 36 epidermal growth factor (EGF)-like repeats in its extracellular domain. This protein functions as a receptor that interacts with other transmembrane proteins, such as Serrate and Delta, which also have EGF repeats in their extracellular domain. The Abruptex mutations of the Notch locus are associated with amino acid substitutions in the EGF repeats 24-29 of the Notch protein. We have studied, in genetic combinations, the modifications of Notch function caused by Abruptex mutations. These mutations lead to phenotypes which are opposite to those caused by Notch deletions. The Abruptex phenotypes are modified by the presence of mutations in other loci, in particular in the genes Serrate and Delta as well as Hairless, and groucho. The results suggest that all Abruptex mutations cause stronger than normal Notch activation by the Delta protein. Some Abruptex alleles also display an insufficiency of N function. Abruptex alleles which produce stronger enhancement of Notch activation also display stronger Notch insufficiency. This insufficiency could be due to reduced ability of Abruptex proteins to interact with Notch ligands and/or to form functional Notch dimers. Centro de Biologia Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain. de Celis J F JF Garcia-Bellido A A eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Hormones 0 Membrane Proteins 0 notch protein 62229-50-9 Epidermal Growth Factor IM Alleles Animal Drosophila melanogaster genetics metabolism physiology Embryo, Nonmammalian physiology Epidermal Growth Factor genetics Female Heterozygote Insect Hormones genetics Male Membrane Proteins genetics Mutation Phenotype Repetitive Sequences, Nucleic Acid Support, Non-U.S. Gov't Wing anatomy & histology growth & development FBrf0156011 22297814 12408844 2002 10 31 2002 11 26

0896-6273 36 3 2002 Oct 24 Unrestricted synaptic growth in spinster-a late endosomal protein implicated in TGF-beta-mediated synaptic growth regulation. 403-16 In a genetic screen for genes that control synapse development, we have identified spinster (spin), which encodes a multipass transmembrane protein. spin mutant synapses reveal a 200% increase in bouton number and a deficit in presynaptic release. We demonstrate that spin is expressed in both nerve and muscle and is required both pre- and postsynaptically for normal synaptic growth. We have localized Spin to a late endosomal compartment and present evidence for altered endosomal/lysosomal function in spin. We also present evidence that synaptic overgrowth in spin is caused by enhanced/misregulated TGF-beta signaling. TGF-beta receptor mutants show dose-dependent suppression of synaptic overgrowth in spin. Furthermore, mutations in Dad, an inhibitory Smad, cause synapse overgrowth. We present a model for synaptic growth control with implications for the etiology of lysosomal storage and neurodegenerative disease. Department of Biochemistry, 513 Parnassus Avenue, HSE 901, University of California, San Francisco, San Francisco, CA 94143, USA. Sweeney Sean T ST Davis Graeme W GW eng 44908-32374 PHS Journal Article

United States Neuron 8809320 0 Drosophila Proteins 0 Membrane Proteins 0 Transforming Growth Factor beta 0 spinster protein, Drosophila IM Neuron. 2002 Oct 24;36(3):335-8 12408836 Animal Cell Compartmentation genetics Cell Differentiation genetics Drosophila Proteins deficiency genetics Drosophila melanogaster cytology growth & development metabolism Endosomes metabolism Female Gene Expression Regulation, Developmental genetics Hela Cells Human Hypertrophy genetics metabolism physiopathology Lysosomes metabolism Male Membrane Proteins deficiency genetics Motor Neurons cytology metabolism Muscle, Skeletal abnormalities growth & development innervation Mutation genetics Nervous System cytology growth & development metabolism Neuromuscular Junction abnormalities growth & development pathology Presynaptic Terminals metabolism pathology ultrastructure Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Synaptic Transmission genetics Transforming Growth Factor beta genetics metabolism FBrf0104795 98384319 9716528 1998 10 30 1998 10 30 2002 10 21

0950-1991 125 18 1998 Sep Interaction between Drosophila EGF receptor and vnd determines three dorsoventral domains of the neuroectoderm. 3625-33 Neurogenesis in Drosophila melanogaster starts by an ordered appearance of neuroblasts arranged in three columns (medial, intermediate and lateral) in each side of the neuroectoderm. Here we show that, in the intermediate column, the receptor tyrosine kinase DER represses expression of proneural genes, achaete and scute, and is required for the formation of neuroblasts. Most of the early function of DER is likely to be mediated by the Ras-MAP kinase signaling pathway, which is activated in the intermediate column, since a loss of a component of this pathway leads to a phenotype identical to that in DER mutants. MAP-kinase activation was also observed in the medial column where esg and proneural gene expression is unaffected by DER. We found that the homeobox gene vnd is required for the expression of esg and scute in the medial column, and show that vnd acts through the negative regulatory region of the esg enhancer that mediates the DER signal, suggesting the role of vnd is to counteract DER-dependent repression. Thus nested expression of vnd and the DER activator rhomboid is crucial to subdivide the neuroectoderm into the three dorsoventral domains. Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. Yagi Y Y Suzuki T T Hayashi S S eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 NK-2 protein 0 Receptors, Invertebrate Peptide 0 Transcription Factors 0 achaete protein, Drosophila 0 epidermal growth factor receptor homolog, Drosophila 0 scute protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase physiology DNA-Binding Proteins biosynthesis genetics Drosophila melanogaster embryology Ectoderm physiology Embryo, Nonmammalian growth & development Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins genetics physiology Nervous System growth & development Phenotype Protein Binding Receptor, Epidermal Growth Factor genetics physiology Receptors, Invertebrate Peptide genetics physiology Signal Transduction Transcription Factors biosynthesis genetics FBrf0087580 96271535 8846898 1996 10 23 1996 10 23 2000 12 18

0016-6731 142 4 1996 Apr Identification and characterization of autosomal genes that interact with glass in the developing Drosophila eye. 1199-213 The glass gene encodes a zinc finger, DNA-binding protein that is required for photoreceptor cell development in Drosophila melanogaster. In the developing compound eye, glass function is regulated at two points: (1) the protein is expressed in all cells' nuclei posterior to the morphogenetic furrow and (2) the ability of the Glass protein to regulate downstream genes is largely limited to the developing photoreceptor cells. We conducted a series of genetic screens for autosomal dominant second-site modifiers of the weal allele glass3, to discover genes with products that may regulate glass function at either of these levels. Seventy-six dominant enhancer mutations were recovered (and no dominant suppressors). Most of these dominant mutations are in essential genes and are associated with recessive lethality. We have assigned these mutations to 23 complementation groups that include multiple alleles of Star and hedgehog as well as single alleles of Delta, roughened eye, glass and hairy. Mutations in 18 of the complementation groups are embryonic lethals, and of these, 13 show abnormal adult retinal phenotypes in homozygous clones, usually with altered numbers of photoreceptor cells in some of the ommatidia. Department of Biological Sciences, University of Southern California, Los Angeles 90089-1340, USA. Ma C C Liu H H Zhou Y Y Moses K K eng 1RO1-EYO-9299 EY NEI Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 glass protein IM Animal Chromosome Mapping DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Genes, Dominant Genes, Insect Genes, Regulator Genetic Complementation Test Male Mutation Photoreceptors, Invertebrate embryology Support, U.S. Gov't, P.H.S. Zinc Fingers genetics FBrf0036522 82211749 6806144 1982 08 26 1982 08 26 2000 12 18

0016-6731 99 3-4 1981 Nov-Dec The distribution of randomly recovered X-ray-induced sex-linked genetic effects in Drosophila melanogaster. 461-80 Cytogenetic analysis of more than 1500 randomly recovered lethal X chromosomes derived from 2000 and 3000 r X-ray exposures of post-meiotic male germ cells has made possible a plot of the distribution in different regions of the X chromosome of: (1) gene mutations associated with cytologically normal chromosomes, (2) mutations associated with chromosomal rearrangement breakpoints, (3) deficiencies, and (4) rearrangement breakpoints whether or not they are associated with mutations. The distribution of point mutations, vital loci and rearrangement breakpoints in different regions of the X chromosome is not proportional to either the number of bands or the relative DNA content. Further, the density of vital loci (those capable of mutating to a lethal allele) is quite different in some regions as compared to others. For example, vital loci in the 3AB region, which has been thoroughly studied by Judd and others, are at least as numerous as bands; whereas, the 3CD region, equally long, has only two vital loci. Other regions densely populated with vital loci include 1B, 1F-2A, 10A, 11A, and 19EF; sparsely populated regions include 6EF and 10B-10E. It seems reasonable to conclude that the recovered X-ray-induced mutants available for analysis do not represent a random sample of those initially induced in the exposed male germ cells. Lefevre G G eng GM-13631 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Aberrations Chromosome Mapping Crosses, Genetic Drosophila melanogaster radiation effects Female Genes, Lethal Genes, Recessive Genetic Complementation Test Linkage (Genetics) Male Mutation Sex Chromosomes radiation effects Support, U.S. Gov't, P.H.S. X Chromosome radiation effects FBrf0152339 22240277 12351791 2002 09 27 2002 10 28 2002 12 10

1095-9203 297 5590 2002 Sep 27 Gene expression during the life cycle of Drosophila melanogaster. 2270-5 Molecular genetic studies of Drosophila melanogaster have led to profound advances in understanding the regulation of development. Here we report gene expression patterns for nearly one-third of all Drosophila genes during a complete time course of development. Mutations that eliminate eye or germline tissue were used to further analyze tissue-specific gene expression programs. These studies define major characteristics of the transcriptional programs that underlie the life cycle, compare development in males and females, and show that large-scale gene expression data collected from whole animals can be used to identify genes expressed in particular tissues and organs or genes involved in specific biological and biochemical processes. Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA. Arbeitman Michelle N MN Furlong Eileen E M EE Imam Farhad F Johnson Eric E Null Brian H BH Baker Bruce S BS Krasnow Mark A MA Scott Matthew P MP Davis Ronald W RW White Kevin P KP eng Journal Article

United States Science 0404511 0 Drosophila Proteins 0 RNA, Messenger IM Science 2002 Nov 8;298(5596):1172 Algorithms Animal Cluster Analysis Drosophila Proteins genetics physiology Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian physiology Female Gene Expression Gene Expression Profiling Gene Expression Regulation, Developmental Genes, Insect Germ Cells physiology Larva genetics Life Cycle Stages genetics Male Oligonucleotide Array Sequence Analysis Organ Specificity Pupa genetics RNA, Messenger genetics metabolism Sex Characteristics Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0134820 21107400 11179818 2001 02 22 2001 06 07

0196-9781 22 2 2001 Feb Neuropeptides and their precursors in the fruitfly, Drosophila melanogaster. 241-54 Neuropeptides form the most diverse class of chemical messenger molecules in metazoan nervous systems. They are usually generated from biosynthetic precursor polypeptides by enzymatic processing and modification. Many different peptides belonging to a number of distinct neuropeptide families have already been characterized from various insect species. The Drosophila Genome Sequencing Project has important implications for the future of neurobiological research. This paper describes the discovery of several new fruitfly neuropeptides by an in silico data mining approach. In addition, the state-of-the-art of Drosophila peptide research is reviewed. Laboratory for Developmental Physiology and Molecular Biology, Zoological Institute, Naamsestraat 59, B-3000 Leuven, Belgium. Jozef.VandenBroeck@bio.kuleuven.ac.be Vanden Broeck J J eng Journal Article

United States Peptides 8008690 0 Insect Proteins 0 Neuropeptides 0 Protein Precursors IM Amino Acid Sequence Animal Drosophila melanogaster genetics metabolism Insect Proteins genetics metabolism Molecular Sequence Data Neuropeptides genetics metabolism Protein Precursors genetics metabolism Support, Non-U.S. Gov't FBrf0134576 21098957 11171395 2001 02 22 2001 04 12 2002 05 20

0950-1991 128 5 2001 Mar Drosophila wing development in the absence of dorsal identity. 703-10 The developing wing disc of Drosophila is divided into distinct lineage-restricted compartments along both the anterior/posterior (A/P) and dorsal/ventral (D/V) axes. At compartment boundaries, morphogenic signals pattern the disc epithelium and direct appropriate outgrowth and differentiation of adult wing structures. The mechanisms by which affinity boundaries are established and maintained, however, are not completely understood. Compartment-specific adhesive differences and inter-compartment signaling have both been implicated in this process. The selector gene apterous (ap) is expressed in dorsal cells of the wing disc and is essential for D/V compartmentalization, wing margin formation, wing outgrowth and dorsal-specific wing structures. To better understand the mechanisms of Ap function and compartment formation, we have rescued aspects of the ap mutant phenotype with genes known to be downstream of Ap. We show that Fringe (Fng), a secreted protein involved in modulation of Notch signaling, is sufficient to rescue D/V compartmentalization, margin formation and wing outgrowth when appropriately expressed in an ap mutant background. When Fng and alphaPS1, a dorsally expressed integrin subunit, are co-expressed, a nearly normal-looking wing is generated. However, these wings are entirely of ventral identity. Our results demonstrate that a number of wing development features, including D/V compartmentalization and wing vein formation, can occur independently of dorsal identity and that inter-compartmental signaling, refined by Fng, plays the crucial role in maintaining the D/V affinity boundary. In addition, it is clear that key functions of the ap selector gene are mediated by only a small number of downstream effectors. The Salk Institute for Biological Studies, PO Box 85800, San Diego, CA 92186, USA. O'Keefe D D DD Thomas J B JB eng Journal Article

England Development 8701744 0 Homeodomain Proteins 0 Insect Proteins 0 Membrane Proteins 0 Trans-Activators 0 Transcription Factors 0 engrail protein, Drosophila 0 notch protein 147756-66-9 apterous protein, Drosophila EC 2.4.- fringe protein IM Animal Body Patterning genetics physiology Cell Differentiation Drosophila melanogaster anatomy & histology genetics growth & development physiology Embryonic Structures anatomy & histology physiology Homeodomain Proteins genetics metabolism Immunohistochemistry Insect Proteins metabolism Membrane Proteins genetics metabolism Phenotype Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism Transcription Factors genetics metabolism Wing anatomy & histology growth & development FBrf0138363 21417218 11526088 2001 08 29 2001 10 11 2002 11 01

0950-1991 128 14 2001 Jul A HOX complex, a repressor element and a 50 bp sequence confer regional specificity to a DPP-responsive enhancer. 2833-45 A central theme during development and homeostasis is the generation of cell type-specific responses to the action of a limited number of extant signaling cascades triggered by extracellular ligands. The molecular mechanisms by which information from such signals are integrated in responding cells in a cell-type specific manner remain poorly understood. We have undertaken a detailed characterization of an enhancer that is regulated by DPP signaling and by the homeotic protein Labial and its partners, Extradenticle and Homothorax. The expression driven by this enhancer (lab550) and numerous deletions and point mutants thereof was studied in wild-type and mutant Drosophila embryos as well as in cultured cells. We find that the lab550 enhancer is composed of two elements, a Homeotic Response Element (HOMRE) and a DPP Response Element (DPPRE) that synergize. None of these two elements can reproduce the expression of lab550, either with regard to expression level or with regard to spatial restriction. The isolated DPPRE of lab550 responds extremely weakly to DPP. Interestingly, we found that the inducibility of this DPPRE is weak because it is tuned down by the action of a repressor element. This repressor element and an additional 50 bp element appear to be crucial for the cooperation of the HOMRE and the DPPRE, and might tightly link the DPP response to the homeotic input. The cooperation between the different elements of the enhancer leads to the segmentally restricted activity of lab550 in the endoderm and provides a mechanism to create specific responses to DPP signaling with the help of a HOX protein complex. Abteilung Zellbiologie, Biozentrum, Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Marty T T Vigano M A MA Ribeiro C C Nussbaumer U U Grieder N C NC Affolter M M eng Journal Article

England Development 8701744 0 DNA, Complementary 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 MAD protein, Drosophila 0 Transcription Factors 0 dpp protein, Drosophila 0 exd protein, Drosophila 0 homothorax protein 125388-07-0 lab protein, Drosophila IM Animal Base Sequence Binding Sites COS Cells Cells, Cultured Cercopithecus aethiops DNA, Complementary DNA-Binding Proteins metabolism Drosophila melanogaster embryology genetics Endoderm Enhancer Elements (Genetics) Gene Expression Genes, Insect Homeodomain Proteins metabolism Insect Proteins metabolism Molecular Sequence Data Response Elements Signal Transduction Support, Non-U.S. Gov't Transcription Factors metabolism FBrf0098376 97460120 9312140 1997 10 22 1997 10 22 2002 11 01

0021-9258 272 40 1997 Oct 3 Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant-negative Zeste-White 3 leads to elevated DE-cadherin in Drosophila clone 8 wing disc cells. 25243-51 Drosophila genetic studies suggest that in the Wingless (Wg) signaling pathway, the segment polarity gene products, Dishevelled (Dsh), Zeste-white 3 (ZW-3), and Armadillo (Arm), work sequentially; wg and dsh negatively regulate zw-3, which in turn down-regulates arm. To biochemically analyze interactions between the Wg pathway and Drosophila E-cadherin (DE-cadherin) which bind to Arm, we overexpressed Dsh, ZW-3, and Arm, in the Drosophila wing disc cell line, clone 8, which responds to Wg signal. Dsh overexpression led to accumulation of Arm primarily in the cytosol and elevation of DE-cadherin at cell junctions. Overexpression of wild-type and dominant-negative forms of ZW-3 decreased and increased Arm levels, respectively, indicating that modulation in zw-3 activity negatively regulates Arm levels. Overexpression of an Arm mutant with an amino-terminal deletion elevated DE-cadherin levels, suggesting that Dsh-induced DE-cadherin elevation is caused by the Arm accumulation induced by Dsh. Moreover, the Dsh-, dominant-negative ZW-3-, and truncated Arm-induced accumulation of DE-cadherin protein was accompanied by a marked increase in the steady-state levels of DE-cadherin mRNA, suggesting that transcription of DE-cadherin is activated by Wg signaling. In addition, overexpression of DE-cadherin elevated Arm levels by stabilizing Arm at cell-cell junctions. Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-Ku, Kyoto, 606 Japan. Yanagawa S i S Lee J S JS Haruna T T Oda H H Uemura T T Takeichi M M Ishimoto A A eng Journal Article

UNITED STATES J Biol Chem 2985121R 0 Cadherins 0 DNA Primers 0 Dsh protein 0 Phosphoproteins 0 Proto-Oncogene Proteins 0 Recombinant Fusion Proteins 0 Recombinant Proteins 117758-26-6 wingless protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 shaggy kinase, Drosophila IM Animal Cadherins biosynthesis Cell Polarity Clone Cells Cloning, Molecular DNA Primers Drosophila melanogaster genetics physiology Genes, Insect Mutagenesis, Site-Directed Phosphoproteins biosynthesis metabolism Protein-Serine-Threonine Kinases biosynthesis metabolism Proto-Oncogene Proteins biosynthesis metabolism Recombinant Fusion Proteins biosynthesis Recombinant Proteins biosynthesis metabolism Signal Transduction Support, Non-U.S. Gov't Transfection Wing FBrf0131272 20519454 11063695 2000 11 21 2001 01 04

0016-6731 156 3 2000 Nov A screen for dominant modifiers of ro(Dom), a mutation that disrupts morphogenetic furrow progression in Drosophila, identifies groucho and hairless as regulators of atonal expression. 1203-17 ro(Dom) is a dominant allele of rough (ro) that results in reduced eye size due to premature arrest in morphogenetic furrow (MF) progression. We found that the ro(Dom) stop-furrow phenotype was sensitive to the dosage of genes known to affect retinal differentiation, in particular members of the hedgehog (hh) signaling cascade. We demonstrate that ro(Dom) interferes with Hh's ability to induce the retina-specific proneural gene atonal (ato) in the MF and that normal eye size can be restored by providing excess Ato protein. We used ro(Dom) as a sensitive genetic background in which to identify mutations that affect hh signal transduction or regulation of ato expression. In addition to mutations in several unknown loci, we recovered multiple alleles of groucho (gro) and Hairless (H). Analysis of their phenotypes in somatic clones suggests that both normally act to restrict neuronal cell fate in the retina, although they control different aspects of ato's complex expression pattern. Department of Anatomy, University of California, San Francisco, California 94143, USA. chanut@itsa.ucsf.edu Chanut F F Luk A A Heberlein U U eng EY11410 EY NEI Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 ato protein 62-50-0 Ethyl Methanesulfonate IM Animal Crosses, Genetic DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology ultrastructure Ethyl Methanesulfonate Female Genes, Dominant Genes, Insect Helix-Loop-Helix Motifs Male Morphogenesis genetics Mutagenesis Phenotype Signal Transduction genetics Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0111527 99408788 10477760 1999 10 14 1999 10 14 2002 11 25

0021-9525 146 5 1999 Sep 6 Apical spectrin is essential for epithelial morphogenesis but not apicobasal polarity in Drosophila. 1075-86 Changes in cell shape and position drive morphogenesis in epithelia and depend on the polarized nature of its constituent cells. The spectrin-based membrane skeleton is thought to be a key player in the establishment and/or maintenance of cell shape and polarity. We report that apical beta(Heavy)-spectrin (beta(H)), a terminal web protein that is also associated with the zonula adherens, is essential for normal epithelial morphogenesis of the Drosophila follicle cell epithelium during oogenesis. Elimination of beta(H) by the karst mutation prevents apical constriction of the follicle cells during mid-oogenesis, and is accompanied by a gross breakup of the zonula adherens. We also report that the integrity of the migratory border cell cluster, a group of anterior follicle cells that delaminates from the follicle epithelium, is disrupted. Elimination of beta(H) prevents the stable recruitment of alpha-spectrin to the apical domain, but does not result in a loss of apicobasal polarity, as would be predicted from current models describing the role of spectrin in the establishment of cell polarity. These results demonstrate a direct role for apical (alphabeta(H))(2)-spectrin in epithelial morphogenesis driven by apical contraction, and suggest that apical and basolateral spectrin do not play identical roles in the generation of apicobasal polarity. Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. Zarnescu D C DC Thomas G H GH eng GM52506 GM NIGMS Journal Article

UNITED STATES J Cell Biol 0375356 0 beta(H)-spectrin, Drosophila 12634-43-4 Spectrin IM Alleles Animal Cell Membrane metabolism Cell Movement Cell Polarity Cytoskeleton metabolism Drosophila melanogaster cytology genetics physiology Epithelium physiology Female Male Morphogenesis Mutation Oogenesis physiology Ovarian Follicle cytology metabolism physiology Phenotype Spectrin genetics metabolism Support, U.S. Gov't, P.H.S. FBrf0064562 94079695 7903039 1994 01 10 1994 01 10 2002 04 19

0264-6021 296 ( Pt 2) 1993 Dec 1 Relocalization of Drosophila dorsal protein can be induced by a rise in cytoplasmic calcium concentration and the expression of constitutively active but not wild-type Toll receptors. 497-503 The generation of dorso-ventral polarity in Drosophila relies on the formation of a nuclear gradient of the rel/nuclear factor kappa B transcription factor dorsal in the pre-cellular syncitial embryo by a process of differential nuclear localization. It is thought that the gradient is formed by activation at ventral positions of the membrane receptor Toll that in turn causes the local dissociation of dorsal from the cytoplasmic anchor protein cactus. Although Toll is related in its cytoplasmic domain to the interleukin-1 receptor little is known about the signal transduction pathways that lead from Toll to the relocalization of dorsal. In this paper we have used immunofluorescence microscopy as a direct assay of dorsal protein nuclear localization in the Drosophila cell line Schneider 2. We find that increased cytoplasmic calcium concentration and the expression of constitutively active Toll receptors can induce the relocalization of dorsal. By contrast, we find that activation of endogenous protein kinase A and expression of wild-type Toll receptors, which activate zen-chloramphenicol acetyltransferase reporter genes in this system, have only a marginal effect on the cellular distribution of the dorsal protein. Treatment of cells with activators of protein kinase C and radical oxygen intermediates, both of which activate nuclear factor kappa B, also has little effect on dorsal protein localization. We propose that different threshold levels of dorsal activation can be established by distinctly regulated signal transduction pathways. Department of Biochemistry, University of Cambridge, U.K. Kubota K K Keith F J FJ Gay N J NJ eng Journal Article

ENGLAND Biochem J 2984726R 0 Androgen-Binding Protein 0 Insect Hormones 0 Membrane Glycoproteins 0 Receptors, Cell Surface 0 Transcription Factors 0 dorsal proteins 118929-01-4 Toll protein, Drosophila 56092-81-0 Ionomycin 60-92-4 Cyclic AMP 66428-89-5 Forskolin 67-42-5 Egtazic Acid 7440-70-2 Calcium EC 2.3.2.13 Transglutaminases EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Androgen-Binding Protein metabolism Animal Calcium metabolism Cell Line Cell Nucleus drug effects metabolism Cyclic AMP metabolism Cyclic AMP-Dependent Protein Kinases metabolism Cytoplasm metabolism Drosophila melanogaster metabolism Egtazic Acid pharmacology Forskolin pharmacology Insect Hormones biosynthesis metabolism Ionomycin pharmacology Membrane Glycoproteins biosynthesis metabolism Receptors, Cell Surface metabolism Signal Transduction Support, Non-U.S. Gov't Transcription Factors metabolism Transfection Transglutaminases metabolism FBrf0149068 22067904 12072176 2002 06 19 2002 08 13

0022-1759 265 1-2 2002 Jul 1 Death to flies: Drosophila as a model system to study programmed cell death. 21-38 Programmed cell death (PCD) is essential for the removal of unwanted cells and is critical for both restricting cell numbers and for tissue patterning during development. Components of the cell death machinery are remarkably conserved through evolution, from worms to mammals. Central to the PCD process is the family of cysteine proteases, known as caspases, which are activated by death-inducing signals. Comparisons between C. elegans and mammalian PCD have shown that there is additional complexity in the regulation of PCD in mammals. The fruitfly, Drosophila melanogaster, is proving an ideal genetically tractable model organism, of intermediary complexity between C. elegans and mammals, in which to study the intricacies of PCD. Here, we review the literature on PCD during Drosophila development, highlighting the methods used in these studies. Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St., Melbourne, Victoria, 8006, Australia. h.richardson@pmci.unimelb.edu.au Richardson Helena H Kumar Sharad S eng Journal Article Review Review, Tutorial

Netherlands J Immunol Methods 1305440 0 Apaf-1 protein 0 Proteins 0 Proto-Oncogene Proteins c-bcl-2 EC 3.4.22.- Caspases IM Animal Apoptosis genetics physiology Caspases physiology Drosophila embryology genetics physiology Models, Animal Proteins physiology Proto-Oncogene Proteins c-bcl-2 physiology Support, Non-U.S. Gov't 118 FBrf0151950 22328947 12441303 2002 11 20 2003 02 04

0950-1991 130 1 2003 Jan Genetic requirements of vestigial in the regulation of Drosophila wing development. 197-208 The gene vestigial has been proposed to act as a master gene because of its supposed capacity to initiate and drive wing development. We show that the ectopic expression of vestigial only induces ectopic outgrowths with wing cuticular differentiation and wing blade gene expression patterns in specific developmental and genetic contexts. In the process of transformation, wingless seems to be an essential but insufficient co-factor of vestigial. vestigial ectopic expression alone or vestigial plus wingless co-expression in clones differentiate 'mixed' cuticular patterns (they contain wing blade trichomes and chaetae characteristic of the endogenous surrounding tissue) and express wing blade genes only in patches of cells within the clones. In addition, we have found that these clones, in the wing imaginal disc, may cause autonomous as well as non-autonomous cuticular transformations and wing blade gene expression patterns. These non-autonomous effects in surrounding cells result from recruitment or 'inductive assimilation' of vestigial or wingless-vestigial overexpressing cells. Centro de Biología Molecular Severo Ochoa-Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Facultad de Ciencias, Madrid 28049, Spain. Baena-López L Alberto LA García-Bellido Antonio A eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Nuclear Proteins 0 Proto-Oncogene Proteins 0 vestigial protein, Drosophila 117758-26-6 wingless protein, Drosophila IM Animal Animals, Genetically Modified Drosophila Proteins genetics metabolism Drosophila melanogaster genetics Gene Expression Regulation, Developmental Larva Nuclear Proteins genetics metabolism Proto-Oncogene Proteins genetics metabolism Support, Non-U.S. Gov't Wing abnormalities growth & development FBrf0130097 20437787 10980431 2000 10 04 2000 10 04 2000 12 18

0959-437X 10 5 2000 Oct Genetic control of cell size. 529-35 Over the past 25 years, the genetic control of cell size has mainly been addressed in yeast, a single-celled organism. Recent insights from Drosophila have shed light on the signalling pathways responsible for adjusting and maintaining cell size in metazoans. Evidence is emerging for a signalling cascade conserved in evolution that links external nutrient sources to cell size. Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. Stocker H H Hafen E E eng Journal Article Review Review, Tutorial

ENGLAND Curr Opin Genet Dev 9111375 0 Proto-Oncogene Proteins c-myc EC 2.7.1.112 Receptor, Insulin EC 2.7.1.137 1-Phosphatidylinositol 3-Kinase EC 3.1.3 Phosphoric Monoester Hydrolases EC 3.1.3.- PTEN protein IM 1-Phosphatidylinositol 3-Kinase metabolism Animal Cell Cycle physiology Cell Size genetics Drosophila melanogaster cytology genetics growth & development Phosphoric Monoester Hydrolases metabolism Proto-Oncogene Proteins c-myc physiology Receptor, Insulin physiology Signal Transduction 76 FBrf0068581 94200046 8149812 1994 05 10 1994 05 10 2000 12 18

0009-5915 102 10 1993 Dec Analysis of Drosophila chromosome 4 using pulsed field gel electrophoresis. 718-23 Previous estimates of the size of Drosophila melanogaster chromosome 4 have indicated that it is 1% to 4% of the genome or approximately 6 Mb. We have used pulsed field gel electrophoresis (PFGE) to separate megabase-sized molecules of D. melanogaster chromosomal DNA. Southern blots of these gels were probed with DNA fragments from the cubitus interruptus and zfh-2 genes, which are located on chromosome 4. They each identify the same-sized distinct band that migrates at approximately 5.2 Mb in DNA preparations from the Kc cell line. We interpret this band to be intact chromosome 4. In DNA obtained from embryos of various D. melanogaster wild-type strains, this chromosome band showed strain-specific size variation that ranged from 4.5 to 5.2 Mb. The D. melanogaster chromosome 4 probes also identified a single, 2.4 Mb band in embryonic DNA from Drosophila simulans. We conclude that D. simulans chromosome 4 is substantially smaller than that of D. melanogaster, presumably owing to differences in the amount of heterochromatic DNA sequences. Our simple DNA preparation from embryos and PFGE conditions should permit preparative isolation of chromosome 4 DNA and will facilitate the molecular mapping of this chromosome. Department of Genetics, University of Alberta, Edmonton, Canada. Locke J J McDermid H E HE eng Journal Article

GERMANY Chromosoma 2985138R 9007-49-2 DNA IM Animal Cell Line DNA analysis Drosophila melanogaster genetics Electrophoresis, Gel, Pulsed-Field Species Specificity Support, Non-U.S. Gov't FBrf0051824 91007256 2120113 1990 11 19 1990 11 19 2000 12 18

0890-9369 4 7 1990 Jul Molecular organization of the decapentaplegic gene in Drosophila melanogaster. 1114-27 The decapentaplegic (dpp) locus of Drosophila melanogaster is a greater than 55 kb genetic unit required for proper pattern formation during the embryonic and imaginal development of the organism. We have proposed that these morphogenetic functions result from the action of a secreted transforming growth factor-beta (TGF-beta)-related protein product encoded by dpp. In this paper we localize 60 mutations on the molecular map of dpp. The positions of these mutations cluster according to phenotypic class, identifying the locations of specific dpp functions. By Northern and cDNA analysis, we characterize five overlapping dpp transcripts. On the basis of the locations of the overlaps relative to a previously sequenced cDNA, it is likely that these transcripts all encode similar or identical polypeptides. We propose that the bulk of dpp DNA consists of extensive arrays of cis-regulatory information. The large (greater than 25-kb) 3' cis-regulatory region represents a novel feature of dpp gene organization Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138-2097. St Johnston R D RD Hoffmann F M FM Blackman R K RK Segal D D Grimaila R R Padgett R W RW Irick H A HA Gelbart W M WM eng Journal Article

UNITED STATES Genes Dev 8711660 0 RNA, Messenger 0 RNA, Transfer, Tyr 9007-49-2 DNA IM Alleles Animal DNA genetics DNA Mutational Analysis Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Gene Expression Regulation Genes, Lethal Genes, Regulator Genes, Structural Morphogenesis Mutation RNA, Messenger genetics RNA, Transfer, Tyr genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0058985 93298648 8518190 1993 07 29 1993 07 29 2000 12 18

0925-4773 41 2-3 1993 May A regulatory function for K10 in the establishment of dorsoventral polarity in the Drosophila egg and embryo. 109-20 Several lines of evidence suggest that the origin of pattern formation of Drosophila embryos must be traced back to oogenesis, to the polarity of the egg chamber. A few early-acting genes, K10, top, grk and cni, have been identified which are assumed to function in a signal transduction process between the germline oocyte and the somatic follicle cells, during which the egg chamber acquires a dorsoventral polarity. K10 has been cloned and was shown to encode a putative transcription factor specifically acting in the oocyte nucleus. In order to characterize further the function of K10, we have analyzed its genetic interactions with grk, top and cni. We show that grk behaves as a dominant partial suppressor of K10. Analysis of the rescuing process of the K10 phenotype by grk shows that: (1) K10 is not indispensable for the establishment of dorsoventral polarity of the egg chamber, since its lack of function can be compensated for by reducing the grk wild-type copy number; (2) grk function is highly dose-sensitive; (3) the rescue process shows an anteroposterior effect suggesting that K10 may also interact with genes involved in anteroposterior pattern formation. These results are compatible with a model in which grk is a dorsalizing signal emanating from the oocyte nucleus, whose level of expression is regulated negatively by the K10 product. Institut Jacques Monod, CNRS, Paris, France. Forlani S S Ferrandon D D Saget O O Mohier E E eng Journal Article

IRELAND Mech Dev 9101218 IM K10 cni dorsal grk top twist Animal Cell Polarity genetics Dosage Compensation (Genetics) Drosophila melanogaster embryology genetics Genes, Regulator Genes, Suppressor Genotype Mutation Ovum ultrastructure Phenotype Support, Non-U.S. Gov't FBrf0057132 93041287 1419850 1992 12 08 1992 12 08 2002 11 01

0925-4773 38 2 1992 Aug Hairless, a Drosophila gene involved in neural development, encodes a novel, serine rich protein. 143-56 Hairless is a dominant loss of function mutation in Drosophila affecting the formation of adult sensory organs. In the mutants, neuronal precursor cells do not differentiate, suggesting that Hairless might be involved in specifying or realizing neuronal fate in the fly, similar to the 'pro-neural' genes of the achaete-scute complex. As highlighted by the manifold phenotypic interactions of Hairless with most of the neurogenic loci, the gene might play an important role in nervous system development. Therefore, we initiated a molecular analysis of the Hairless locus in order to elucidate the function of its gene product and gain insight into the biochemical nature of the observed genetic interactions in which it participates. Here, we report the molecular cloning of the Hairless locus, confirmed by breakpoint and transformation analysis. Unexpectedly, Hairless activity peaks during embryogenesis, where transcripts accumulate primarily in endo- and mesodermal cell layers, and is lowest during larval stages, the lethal phase of Hairless mutants. The putative Hairless protein deduced from DNA sequencing is extremely basic and highly enriched in serine residues. Hairless appears to encode a novel protein without compelling homology to other known proteins which function in specifying peripheral nervous system development in Drosophila. Biozentrum, Department of Cellbiology, University of Basel, Switzerland. Maier D D Stumm G G Kuhn K K Preiss A A eng Journal Article

IRELAND Mech Dev 9101218 0 Proteins 148349-66-0 Hairless protein, Drosophila 56-45-1 Serine 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence DNA genetics Drosophila melanogaster embryology genetics Embryo and Fetal Development Endoderm metabolism Female Genes, Lethal Genes, Recessive Genes, Structural Infertility, Female genetics Larva Mesoderm metabolism Molecular Sequence Data Morphogenesis Proteins genetics physiology Sense Organs embryology Serine analysis Support, Non-U.S. Gov't Transcription, Genetic Wing abnormalities FBrf0093161 97261951 9108365 1997 05 05 1997 05 05 2000 12 18

0950-1991 124 8 1997 Apr The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate. 1485-95 We have investigated the role of the Notch and Wingless signaling pathways in the maintenance of wing margin identity through the study of cut, a homeobox-containing transcription factor and a late-arising margin-specific marker. By late third instar, a tripartite domain of gene expression can be identified about the dorsoventral compartment boundary, which marks the presumptive wing margin. A central domain of cut- and wingless-expressing cells are flanked on the dorsal and ventral side by domains of cells expressing elevated levels of the Notch ligands Delta and Serrate. We show first that cut acts to maintain margin wingless expression, providing a potential explanation of the cut mutant phenotype. Next, we examined the regulation of cut expression. Our results indicate that Notch, but not Wingless signaling, is autonomously required for cut expression. Rather, Wingless is required indirectly for cut expression; our results suggest this requirement is due to the regulation by wingless of Delta and Serrate expression in cells flanking the cut and wingless expression domains. Finally, we show that Delta and Serrate play a dual role in the regulation of cut and wingless expression. Normal, high levels of Delta and Serrate can trigger cut and wingless expression in adjacent cells lacking Delta and Serrate. However, high levels of Delta and Serrate also act in a dominant negative fashion, since cells expressing such levels cannot themselves express cut or wingless. We propose that the boundary of Notch ligand along the normal margin plays a similar role as part of a dynamic feedback loop that maintains the tripartite pattern of margin gene expression. Department of Zoology, University of Wisconsin, Madison 53706, USA. Micchelli C A CA Rulifson E J EJ Blair S S SS eng R01-NS28202 NS NINDS Journal Article

ENGLAND Development 8701744 0 Cut protein 0 Homeodomain Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Nuclear Proteins 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 notch protein 117758-26-6 wingless protein, Drosophila 134324-36-0 Serrate protein IM Animal Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Dominant Genes, Homeobox Homeodomain Proteins physiology Membrane Proteins physiology Nerve Tissue Proteins physiology Nuclear Proteins physiology Proto-Oncogene Proteins physiology Repressor Proteins physiology Signal Transduction Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Wing embryology FBrf0043486 86094242 3001704 1986 02 07 1986 02 07 2000 12 18

0027-8424 82 24 1985 Dec Identification of a novel receptor in Drosophila for both epidermal growth factor and insulin. 8443-7 The notable amino acid homology among mammalian growth factor receptors with tyrosine-specific protein kinase activity has led to speculation that these receptors derived from a common evolutionary precursor. We report the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100-kDa protein is also related antigenically to the mammalian receptors for EGF and possibly insulin but may not correspond to the mammalian counterpart of either receptor in Drosophila. The Drosophila protein is recognized by antisera directed against the mammalian receptor for EGF in immunoblot hybridizations. It can be affinity labeled with either 125I-labeled insulin or 125I-labeled EGF after immunoprecipitation with anti-EGF receptor antiserum. Excess unlabeled EGF or insulin will block the affinity labeling with either growth factor, suggesting that both EGF and insulin share a common binding site on the 100-kDa Drosophila receptor. This Drosophila protein, therefore, may be closely related to an evolutionary precursor of the mammalian receptors for insulin and EGF. Thompson K L KL Decker S J SJ Rosner M R MR eng CA35541 CA NCI CA37754 CA NCI T32-ES07020 ES NIEHS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Affinity Labels 0 Growth Substances 0 Membrane Proteins 0 Receptors, Cell Surface EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.112 Receptor, Insulin IM Affinity Labels Animal Cell Line Cross Reactions Drosophila melanogaster analysis genetics Evolution Growth Substances metabolism Immunologic Techniques Membrane Proteins immunology metabolism Molecular Weight Receptor, Epidermal Growth Factor Receptor, Insulin immunology metabolism Receptors, Cell Surface immunology metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0074846 94304407 8031300 1994 08 05 1994 08 05 2000 12 18

0265-9247 16 4 1994 Apr Signaling mechanisms in induction of the R7 photoreceptor in the developing Drosophila retina. 237-44 The Drosophila compound eye is an excellent experimental system for analysing fate induction of identifiable single cells. Each ommatidium, a unit eye, contains eight photoreceptors (R1-R8), and the differentiation of these photoreceptors occurs in the larval eye imaginal disc in discrete steps: first R8 is determined, then R2/R5, R3/R4, R1/R6 and finally R7. Induction of R7, in particular, has been extensively studied at the molecular level. The R8 photoreceptor presents on its surface a ligand, Bride of Sevenless, that binds and activates Sevenless receptor tyrosine kinase in the R7 precursor. Autophosphorylated Sevenless initiates a Ras1-mediated cascade, which eventually activates transcription factors in the nucleus via Raf1 and MAP kinases, resulting in R7 development. However, recent studies indicate that Sevenless (Sev) functions just to neuralize the cell and has no role in R7 fate determination per se. It appears that the R7 fate may represent the lowest rung of a 'neuronal ground state', which is attained without any specific inductive cue. It is plausible that the R7 precursor is actively prevented from taking on the neuronal fate and this inhibition is removed by activation of Sev. Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan. Yamamoto D D eng Journal Article Review Review, Tutorial

ENGLAND Bioessays 8510851 0 Eye Proteins 0 Membrane Glycoproteins 0 Proto-Oncogene Proteins 0 bride of sevenless protein 0 sevenless protein EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 3.6.1.- GTP-Binding Proteins IM Dsor 1 GapI Raf1 Sos boss c-jun c-raf-1 drk en eve ftz mip pok raf 1 ras 1 ras 2 rl ro sev sextra sina svp ttk yan Animal Drosophila melanogaster embryology genetics physiology Eye Proteins physiology GTP-Binding Proteins metabolism Genes, Structural, Insect Membrane Glycoproteins physiology Models, Biological Morphogenesis Photoreceptors, Invertebrate embryology metabolism Protein-Serine-Threonine Kinases metabolism Proto-Oncogene Proteins metabolism Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases physiology Retina embryology Signal Transduction Support, Non-U.S. Gov't 56 FBrf0099885 98088691 9428415 1998 02 02 1998 02 02 2000 12 18

0950-1991 124 23 1997 Dec Establishing primordia in the Drosophila eye-antennal imaginal disc: the roles of decapentaplegic, wingless and hedgehog. 4793-800 The eye-antennal imaginal discs of Drosophila melanogaster form the head capsule of the adult fly. Unlike the limb primordia, each eye-antennal disc gives rise to morphologically and functionally distinct structures. As a result, these discs provide an excellent model system for determining how the fates of primordia are specified during development. In this study, we investigated how the adjacent primordia of the compound eye and dorsal head vertex are specified. We show that the genes wingless (wg) and orthodenticle (otd) are expressed throughout the entire second instar eye-antennal disc, conferring a default fate of dorsal vertex cuticle. Activation of decapentaplegic (dpp) expression in the posterior eye disc eliminates wg and otd expression, thereby permitting eye differentiation. We also demonstrate that otd is activated by wg in the vertex primordium. Finally, we show that early activation of dpp depends on hedgehog (hh) expression in the eye anlage prior to morphogenetic furrow formation. Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. Royet J J Finkelstein R R eng 5R01 GM47985 GM NIGMS Journal Article

ENGLAND Development 8701744 0 Homeodomain Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 dpp protein, Drosophila 0 orthodenticle protein 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Drosophila melanogaster growth & development Eye growth & development Gene Expression Regulation, Developmental Head growth & development Homeodomain Proteins physiology Insect Proteins physiology Larva Proto-Oncogene Proteins physiology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0151932 22283639 12397110 2002 10 24 2002 12 03 2003 06 16

0950-1991 129 21 2002 Nov The Hox gene abdominal-A specifies heart cell fate in the Drosophila dorsal vessel. 5019-27 The Drosophila melanogaster dorsal vessel is a linear organ that pumps blood through the body. Blood enters the dorsal vessel in a posterior chamber termed the heart, and is pumped in an anterior direction through a region of the dorsal vessel termed the aorta. Although the genes that specify dorsal vessel cell fate are well understood, there is still much to be learned concerning how cell fate in this linear tube is determined in an anteroposterior manner, either in Drosophila or in any other animal. We demonstrate that the formation of a morphologically and molecularly distinct heart depends crucially upon the homeotic segmentation gene abdominal-A (abd-A). abd-A expression in the dorsal vessel was detected only in the heart, and overexpression of abd-A induced heart fate in the aorta in a cell-autonomous manner. Mutation of abd-A resulted in a loss of heart-specific markers. We also demonstrate that abd-A and sevenup co-expression in cardial cells defined the location of ostia, or inflow tracts. Other genes of the Bithorax Complex do not appear to participate in heart specification, although high level expression of Ultrabithorax is capable of inducing a partial heart fate in the aorta. These findings for the first time demonstrate a specific involvement for Hox genes in patterning the muscular circulatory system, and suggest a mechanism of broad relevance for animal heart patterning. Department of Biology, University of New Mexico, Albuquerque 87131-1091, USA. Lovato TyAnna L TL Nguyen Thiennga P TP Molina Marco R MR Cripps Richard M RM eng Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila IM Animal Aorta embryology Body Patterning genetics DNA-Binding Proteins genetics Drosophila Proteins genetics Drosophila melanogaster cytology embryology genetics Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Heart embryology Muscle, Skeletal embryology Myocardium cytology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0131266 20555482 11105896 2001 02 14 2001 03 08 2002 10 21

1084-9521 11 5 2000 Oct Runt and Lozenge function in Drosophila development. 327-36 Runt and Lozenge (LZ) are members of the Runt domain family of transcriptional regulators and control a large number of developmental processes in Drosophila. Runt is a pair-rule gene, and is part of the network of genes that control pattern formation in the embryo. In the central nervous system, Runt function is necessary for the development of a subset of neurons. Runt is also a key regulator of sex determination, and directly controls Sex-lethal, a master gene that determines sex of the animal and controls dosage compensation. The LZ protein also participates in several key processes. LZ controls pre-patterning and cell-fate choices in the development of the visual system by regulating the expression of several fate-specifying transcription factors, and works in conjunction with general signaling pathways. LZ function is also required in hematopoiesis for the specification of a Drosophila blood cell lineage. Department of Biological Chemistry, Molecular Biology Institute, University of California at Los Angeles, 90095, USA. Canon J J Banerjee U U eng GM07185 GM NIGMS RO1EY08152 EY NEI Journal Article Review Review, Tutorial

ENGLAND Semin Cell Dev Biol 9607332 0 DNA-Binding Proteins 0 Runt protein 0 Transcription Factors 0 lozenge protein, Drosophila IM Animal Body Patterning genetics physiology DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics growth & development Eye embryology growth & development Female Gene Expression Regulation, Developmental Male Sex Determination (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism Transcription, Genetic 70 FBrf0132416 21003813 11117736 2000 12 14 2000 12 22 2003 06 16

0028-0836 408 6812 2000 Nov 30 Genetic control and evolution of sexually dimorphic characters in Drosophila. 553-9 Sexually dimorphic abdominal pigmentation and segment morphology evolved recently in the melanogaster species group of the fruitfly Drosophila. Here we show that these traits are controlled by the bric à brac [corrected] (bab) gene, which integrates regulatory inputs from the homeotic and sex-determination pathways. bab expression is modulated segment- and sex-specifically in sexually dimorphic species, but is uniform in sexually monomorphic species. We suggest that bab has an ancestral homeotic function, and that regulatory changes at the bab locus played a key role in the evolution of sexual dimorphism. Pigmentation patterns specified by bab affect mating preferences, suggesting that sexual selection has contributed to the evolution of bab regulation. Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, 53706-1596, USA. Kopp A A Duncan I I Godt D D Carroll S B SB eng Journal Article

England Nature 0410462 0 Bric-a-brac protein 1, Drosophila 0 DNA-Binding Proteins 0 Insect Proteins 0 Transcription Factors 0 doublesex protein, Drosophila IM Nature. 2000 Nov 30;408(6812):529, 531 11117726 Nature. 2002 Sep 26;419(6905):360; discussion 360 12353025 Nature 2001 Mar 29;410(6828):611 Animal DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Evolution Evolution, Molecular Female Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Insect Proteins genetics Male Models, Genetic Pigmentation genetics Reproduction Sex Characteristics Sex Differentiation genetics Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics FBrf0042044 85124611 2982499 1985 04 24 1985 04 24 2000 12 18

0092-8674 40 3 1985 Mar The Drosophila EGF receptor gene homolog: conservation of both hormone binding and kinase domains. 599-607 Chicken v-erB probe was used to isolate a unique clone of Drosophila melanogaster DNA. It maps by in situ hybridization to position 57F on chromosome 2. A complete nucleotide sequence of the coding region has been obtained. The putative Drosophila EGF receptor protein is similar in overall organization to the human homolog. It shows three distinct domains: an extracellular putative EGF binding domain, a hydrophobic transmembrane region, and a cytoplasmic kinase domain. The overall amino acid homology is 41% in the extracellular domain and 55% in the kinase domain. Two cysteine-rich regions, a hallmark of the human ligand-binding domain, have also been conserved. Fusion of the coding sequences of the kinase and extracellular domains generating the receptor gene must have occurred over 800 million years ago. Livneh E E Glazer L L Segal D D Schlessinger J J Shilo B Z BZ eng GENBANK K03054 CA25820 CA NCI Journal Article

UNITED STATES Cell 0413066 0 DNA, Recombinant 0 Receptors, Cell Surface 62229-50-9 Epidermal Growth Factor EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Protein Kinases IM Amino Acid Sequence Animal Bacteriophages genetics Base Sequence Chickens genetics Chromosome Mapping Comparative Study Cytoplasm DNA, Recombinant Drosophila melanogaster genetics Epidermal Growth Factor metabolism Evolution Human Nucleic Acid Hybridization Phosphorylation Protein Kinases genetics Protein-Tyrosine Kinase Receptor, Epidermal Growth Factor Receptors, Cell Surface genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0056260 92258692 1349870 1992 06 12 1992 06 12 2000 12 18

0016-6731 130 4 1992 Apr Molecular genetics of the Drosophila melanogaster ovo locus, a gene required for sex determination of germline cells. 791-803 The Drosophila melanogaster ovo gene is required for survival and differentiation of female germline cells, apparently playing a role in germline sex determination. We recovered 60 kb of genomic DNA from its genetic location at 4E1,2 on the X chromosome. A transcription unit coding for an apparently female-specific germline-dependent 5-kb poly(A)+ RNA size class is located substantially in a 7-kb region, within which three DNA-detectable lesions for mutations that inactivate the ovo function are located at two sites approximately 4 kb apart. The breakpoint of a deficiency that removes the neighboring lethal complementation group shavenbaby (svb) but leaves the ovo function intact maps approximately 5 kb to the molecular left of the leftmost ovo mutant site. A class of mutations that inactivates both the svb function and the ovo function affects genomic DNA between the two ovo sites. Sequences required for the two genetic functions are partly overlapping. In spite of this overlap, P element-mediated gene transfer of a 10-kb genomic DNA segment containing the 5-kb poly(A)+ RNA transcription unit rescues the female sterility phenotypes of ovo mutations, but not the svb lethality. Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637. Garfinkel M D MD Lohe A R AR Mahowald A P AP eng R01 HD17608 HD NICHD T32 HD07104 HD NICHD Journal Article

UNITED STATES Genetics 0374636 0 RNA, Messenger 24937-83-5 Poly A IM ovo svb Animal Chromosome Walking Cloning, Molecular Drosophila melanogaster genetics Genes, Lethal genetics Germ Cells growth & development Mutation genetics Poly A genetics RNA, Messenger genetics Repetitive Sequences, Nucleic Acid Sex Determination (Analysis) Support, U.S. Gov't, P.H.S. Transcription, Genetic genetics FBrf0132296 21064441 11124124 2001 01 26 2001 02 22 2001 11 02

0950-1991 128 2 2001 Jan The EGF receptor and N signalling pathways act antagonistically in Drosophila mesothorax bristle patterning. 299-308 An early step in the development of the large mesothoracic bristles (macrochaetae) of Drosophila is the expression of the proneural genes of the achaete-scute complex (AS-C) in small groups of cells (proneural clusters) of the wing imaginal disc. This is followed by a much increased accumulation of AS-C proneural proteins in the cell that will give rise to the sensory organ, the SMC (sensory organ mother cell). This accumulation is driven by cis-regulatory sequences, SMC-specific enhancers, that permit self-stimulation of the achaete, scute and asense proneural genes. Negative interactions among the cells of the cluster, triggered by the proneural proteins and mediated by the Notch receptor (lateral inhibition), block this accumulation in most cluster cells, thereby limiting the number of SMCs. Here we show that the proneural proteins trigger, in addition, positive interactions among cells of the cluster that are mediated by the Epidermal growth factor receptor (EGFR) and the Ras/Raf pathway. These interactions, which we denominate 'lateral co-operation', are essential for macrochaetae SMC emergence. Activation of the EGFR/Ras pathway appears to promote proneural gene self-stimulation mediated by the SMC-specific enhancers. Excess EGFR signalling can overrule lateral inhibition and allow adjacent cells to become SMCs and sensory organs. Thus, the EGFR and Notch pathways act antagonistically in notum macrochaetae determination. Centro de Biología Molecular Severo Ochoa, CSIC and UAM, Cantoblanco, Madrid, Spain. Culí J J Martín-Blanco E E Modolell J J eng Journal Article

England Development 8701744 EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 3.6.1.- ras Proteins IM Animal Animals, Genetically Modified Body Patterning genetics Drosophila melanogaster genetics growth & development metabolism Genes, Insect In Situ Hybridization Models, Biological Receptor, Epidermal Growth Factor metabolism Sense Organs growth & development metabolism Signal Transduction Support, Non-U.S. Gov't Wing growth & development ras Proteins metabolism FBrf0058613 94040679 8224812 1993 12 01 1993 12 01 2000 12 18

0016-6731 135 1 1993 Sep Genetic and cytogenetic analysis of the 43A-E region containing the segment polarity gene costa and the cellular polarity genes prickle and spiny-legs in Drosophila melanogaster. 105-15 A cytogenetic analysis of the 43A-E region of chromosome 2 in Drosophila melanogaster is presented. Within this interval 27 complementation groups have been identified by extensive F2 screens and ordered by deletion mapping. The region includes the cellular polarity genes prickle and spiny-legs, the segmentation genes costa and torso, the morphogenetic locus sine oculis and is bounded on its distal side by the eye-color gene cinnabar. In addition 19 novel lethal complementation groups and two semi-lethal complementation groups with morphogenetic escaper phenotypes are described. Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médicine, Strasbourg, France. Heitzler P P Coulson D D Saenz-Robles M T MT Ashburner M M Roote J J Simpson P P Gubb D D eng Journal Article

UNITED STATES Genetics 0374636 IM cn cos pk so sple tor Alleles Animal Drosophila melanogaster genetics Female Gene Deletion Gene Rearrangement Genes, Lethal Genetic Complementation Test Male Mutation Phenotype Support, Non-U.S. Gov't FBrf0087740 96210622 8633045 1996 07 01 1996 07 01 2002 04 19

0027-8424 93 9 1996 Apr 30 Phosphorylation of the fused protein kinase in response to signaling from hedgehog. 4224-8 The hedgehog gene (hh) of Drosophila melanogaster exerts both short- and long-range effects on cell patterning during development. The product of hedgehog is a secreted protein that apparently acts by triggering an intra-cellular signaling pathway, but little is known about the details of that pathway. The Drosophila gene fused (fu) encodes a serine/threonine-protein kinase that genetic experiments have implicated in signaling initiated by hedgehog. Here we report that the fused protein is phosphorylated during the course of Drosophila embryogenesis, as a result of hedgehog activity. In cell culture, phosphorylation of fused protein occurs in response to the biologically active form of hedgehog and cannot be blocked by activation of protein kinase A, which is thought to be an antagonist of signaling from hedgehog. These results suggest that fused and protein kinase A function downstream of hedgehog but in parallel pathways that eventually converge distal to fused. The reconstruction of signaling from hedgehog in cell culture should provide further access to the mechanisms by which hedgehog acts. G.W. Hooper Research Foundation, San Francisco, CA 94143-0552, USA. Thérond P P PP Knight J D JD Kornberg T B TB Bishop J M JM eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Proteins 0 Recombinant Fusion Proteins 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Cell Line Cyclic AMP-Dependent Protein Kinases metabolism Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian physiology Genes, Insect Kinetics Morphogenesis Phosphorylation Protein-Serine-Threonine Kinases biosynthesis isolation & purification metabolism Proteins biosynthesis isolation & purification metabolism Recombinant Fusion Proteins biosynthesis isolation & purification metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0083926 96122895 8562420 1996 03 07 1996 03 07 2000 12 18

0925-4773 53 2 1995 Oct Expression of protein tyrosine phosphatase genes during oogenesis in Drosophila melanogaster. 171-83 The spatial and temporal expression of seven Drosophila protein tyrosine phosphatase genes during oogenesis was examined by whole mount in-situ hybridization of antisense RNA probes to ovaries. Our observations indicate diverse expression patterns consistent with multiple roles for protein tyrosine phosphatases in the ovary. DPTP99A and corkscrew transcripts are expressed in follicle cells, consistent with possible roles in the EGF receptor signaling pathway. Transcripts from corkscrew and DPTP10D are detected in the germline during oogenesis and localized to the oocyte during egg chamber development. Localization of the two transcripts is disrupted by mutations in egalitarian and Bicaudal D. DLAR and DPTP4E transcripts are found in the germline during the same developmental stages as DPTP10D transcripts, but their transcripts are not localized to the oocyte. DPTP61F transcription is detected only after stage 6 of oogenesis. After stage 10B these transcripts are transported to the oocyte; thus ovarian transcription of DPTP61F may reflect a maternal contribution of the mRNA for later use during embryogenesis. DPTP69D transcripts are sequestered in the nucleus from stage 7 to stage 10, and then released to the cytoplasm. Our observations suggest that the export of DPTP69D mRNA from the nucleus is temporally regulated during oogenesis. Institute of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada. Fitzpatrick K A KA Gorski S M SM Ursuliak Z Z Price J V JV eng Journal Article

IRELAND Mech Dev 9101218 0 RNA Probes 0 RNA, Antisense 0 RNA, Messenger EC 3.1.3.48 Protein-Tyrosine-Phosphatase IM Animal Base Sequence Drosophila melanogaster genetics Gene Expression Regulation, Enzymologic physiology In Situ Hybridization Molecular Sequence Data Oocytes metabolism Oogenesis genetics Protein-Tyrosine-Phosphatase genetics RNA Probes RNA, Antisense RNA, Messenger metabolism Support, Non-U.S. Gov't FBrf0055868 93048804 1358590 1992 12 03 1992 12 03 2000 12 18

0950-1991 115 2 1992 Jun Gonad formation and development requires the abd-A domain of the bithorax complex in Drosophila melanogaster. 395-402 The abdominal-A (abd-A) gene, a member of the bithorax complex, is required for the correct identity of parasegments (PS) 7 through 13. Mutations in iab-4, one of the cis-regulatory regions of abd-A, transform epidermal structures of PS 9 and also cause loss of gonads in adult flies. Here, we describe a developmental and molecular analysis of the role of iab-4 functions in gonadal development. In flies homozygous for a strong iab-4 allele, gonadogenesis is not initiated in the embryo because the mesodermal cells fail to encapsulate the pole cells. Flies homozygous for weaker iab-4 mutations sometimes form ovaries. The ovary-oviduct junctions are abnormal, however, and egg transfer from the ovary to the uterus is blocked in the adult. To localize the sites that require iab-4 function, we have analyzed animals chimeric for the mutant and wild-type cells. These chimeras were generated by three kinds of transplantation experiments: pole cells, embryonic somatic nuclei or larval ovaries. Our results suggest that iab-4 is required in the somatic cells of the gonadal primordia, but not the germ line. In addition, the formation of functional ovary-oviduct junctions and egg transfer also requires iab-4 functions in the somatic cells of the ovary and in at least one additional somatic tissue. Howard Hughes Medical Institute, Department of Human Genetics, University of Utah, Salt Lake City 84112. Cumberledge S S Szabad J J Sakonju S S eng Journal Article

ENGLAND Development 8701744 IM abd-A Animal Cell Nucleus transplantation Chimera genetics Drosophila melanogaster anatomy & histology embryology genetics Female Gene Expression genetics Genes, Homeobox physiology Immunohistochemistry Male Mesoderm physiology Mutation genetics Ovary anatomy & histology embryology transplantation Testis anatomy & histology embryology FBrf0082225 95254650 7736592 1995 06 07 1995 06 07 2003 06 16

0092-8674 81 3 1995 May 5 Translational regulation of oskar mRNA by bruno, an ovarian RNA-binding protein, is essential. 403-12 Oskar (osk) protein directs the deployment of nanos (nos), the posterior body-patterning morphogen in Drosophila. To avoid inappropriate activation of nos, osk activity must appear only at the posterior pole of the oocyte, where the osk mRNA becomes localized during oogenesis. Here, we show that translation of osk mRNA is, and must be, repressed prior to its localization; absence of repression allows osk protein to accumulate throughout the oocyte, specifying posterior body patterning throughout the embryo. Translational repression is mediated by an ovarian protein, bruno, that binds specifically to bruno response elements (BREs), present in multiple copies in the osk mRNA 3'UTR. Addition of BREs to a heterologous mRNA renders it sensitive to translational repression in the ovary. Department of Biological Sciences, Stanford University, California 94305-5020, USA. Kim-Ha J J Kerr K K Macdonald P M PM eng Journal Article

UNITED STATES Cell 0413066 0 Egg Proteins 0 Insect Hormones 0 Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 aret protein, Drosophila 0 oskar protein, Drosophila 142661-95-8 nanos protein, Drosophila 144998-54-9 exuperantia protein, Drosophila IM exu nos osk Animal Base Sequence Binding Sites Cell Compartmentation Drosophila melanogaster embryology genetics Egg Proteins genetics Embryology Female Gene Expression Regulation Insect Hormones metabolism Molecular Sequence Data Mutation Oocytes physiology Ovary cytology physiology Protein Binding Proteins biosynthesis genetics RNA, Messenger biosynthesis RNA-Binding Proteins genetics metabolism Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't Translation, Genetic FBrf0096024 97391237 9248044 1997 09 08 1997 09 08 2000 12 18

1341-7568 72 1 1997 Feb Genetic variation in the expression of the six hsp genes in the presence of heat shock in Drosophila melanogaster. 19-24 Genetic variation in total mRNA level of the six hsp genes (hsp22, hsp23, hsp26, hsp27, hsp70 and hsp82) in the presence of heat shock was investigated by using seventy-four second- and seventy third-chromosome lines of Drosophila melanogaster which have the same genetic background derived from a highly inbred stock. There was significant variation in all the six hsp genes for both the second- and third-chromosome lines except for the hsp22 gene of the third-chromosome lines. Although all the structural genes of the heat shock proteins are localized on the third chromosome, the estimates of genetic variance for the second-chromosome lines were larger than those for the third-chromosome lines. Highly significant correlations between total mRNA level of the different hsp genes in all the combinations of the six hsp genes using the second-chromosome lines were found, but some of correlations for the third-chromosome lines were not significant. These results suggest that some second chromosome variants have similar effects on the expression of the different genes. Division of Medical Zoology, Oita Medical University, Japan. Otsuka Y Y Takano T S TS Yamazaki T T eng Journal Article

JAPAN Genes Genet Syst 9607822 0 Heat-Shock Proteins 0 RNA, Messenger IM Animal Chromosomes Drosophila melanogaster genetics Female Gene Expression Regulation Genetics, Population Heat Heat-Shock Proteins genetics Homozygote Inbreeding Male Phenotype RNA, Messenger Support, Non-U.S. Gov't Variation (Genetics) FBrf0058131 93209209 8384551 1993 04 23 1993 04 23 2000 12 18

0261-4189 12 3 1993 Mar The bluetail transposon: evidence for independent cis-regulatory domains and domain boundaries in the bithorax complex. 1087-97 An extremely large cis-regulatory region generates the parasegment-specific expression patterns of the homeotic genes in the bithorax complex. We present evidence supporting the idea that this cis-regulatory region is subdivided into independent cis-regulatory domains. We describe a Ubx-lacZ transposon which is inserted into one of these domains, iab-7. The PS12-specific pattern of LacZ expression from this reporter indicates that it is subject to the control of the iab-7 cis-regulatory domain, but is protected from the effects of adjacent regulatory domains. Protection on the proximal side appears to be provided by the Fab-7 boundary element. Deletion of this boundary results in the ectopic activation of iab-7 in PS11 (where the iab-6 cis-regulatory domain normally functions). We show that the Fab-7 boundary, like other boundaries, has an unusual chromatin structure. Department of Zoology and Animal Biology, University of Geneva, Switzerland. Galloni M M Gyurkovics H H Schedl P P Karch F F eng Journal Article

ENGLAND EMBO J 8208664 0 Chromatin 0 DNA Transposable Elements 0 RNA, Messenger EC 3.2.1.23 beta-Galactosidase IM Fab-7 Ubx iab lacZ Animal Chromatin chemistry DNA Transposable Elements Drosophila melanogaster Larva Mutation RNA, Messenger genetics Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Thorax embryology beta-Galactosidase genetics FBrf0152001 22217800 12231627 2002 09 16 2002 10 17 2002 11 14

0890-9369 16 18 2002 Sep 15 Negative regulation of STAT92E by an N-terminally truncated STAT protein derived from an alternative promoter site. 2379-89 Previously unrecognized mRNAs originating from a dual promoter at the stat92E locus are described. One of these encodes a truncated protein, DeltaNSTAT92E, that lacks the N-terminal 133 amino acids. Antibodies detect both the full-length and truncated molecules early in embryogenesis (1-5 h), and mRNA detection by specific RT-PCR reactions accords with the protein distribution. Given that the N termini of mammalian STATs are known to have positive functions in transcriptional activation, we explored the role of DeltaNSTAT92E early in embryogenesis. By increasing the DeltaNSTAT92E-to-STAT92E ratio in overexpression and RNAi experiments, we observe phenotypes compatible with suppression of wild-type STAT92E activity. We therefore conclude that the short form of STAT92E is a naturally occurring dominant-negative product that can be added to the growing list of negative regulators of STAT activity. Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021, USA. Henriksen Melissa A MA Betz Aurel A Fuccillo Marc V MV Darnell James E JE Jr eng AI32489 AI NIAID AI34420 AI NIAID Journal Article

United States Genes Dev 8711660 0 DNA-Binding Proteins 0 Drosophila Proteins 0 RNA, Messenger 0 STAT92E protein 0 Trans-Activators 9007-49-2 DNA IM Genes Dev 2002 Oct 15;16(20):2729 Alternative Splicing Animal Base Sequence Cell Line DNA genetics DNA-Binding Proteins chemistry genetics metabolism Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster embryology genetics metabolism Gene Expression Regulation, Developmental Genes, Insect Molecular Sequence Data Promoter Regions (Genetics) RNA, Messenger genetics metabolism Support, U.S. Gov't, P.H.S. Trans-Activators chemistry genetics metabolism FBrf0048766 89070683 2904655 1989 01 18 1989 01 18 2000 12 18

0028-0836 336 6199 1988 Dec 8 Drosophila homoeotic genes encode transcriptional activators similar to mammalian OTF-2. 598-601 Homoeotic genes in Drosophila melanogaster are active in spatially restricted metameric domains and control the morphogenesis of segment-specific features such as legs or wings within these domains. They exert their function, according to the 'selector gene' hypothesis, by regulating the expression of subordinate genes. Homoeotic genes also control their own expression and the expression of each other. The proteins encoded by these genes contain a domain, called a homoeodomain, that is strongly conserved, and that shows homologies to proteins that bind DNA and regulate transcription. Homoeoproteins have been shown to bind specific DNA sequences. We show here that the Drosophila homoeotic genes Ultrabithorax (Ubx) and Abdominal-B (Abd-B) code for proteins that are capable of activating transcription of reporter genes linked to specific cis-regulatory target sequences in transfected mammalian cells. Their activity, as well as their target specificity, is similar to that of a mammalian lymphoid-specific octamer transcription factor, OTF-2, which was recently found to contain a homoeodomain. Arbeitsgruppe Walter Schaffner, Institut für Molekularbiologie II, Universität Zürich, Switzerland. Thali M M Müller M M MM DeLorenzi M M Matthias P P Bienz M M eng Journal Article

ENGLAND Nature 0410462 0 Plasmids 0 Transcription Factors 0 octamer transcription factor OTF-2 IM Nature 1989 Jan 19;337(6204):290 Animal Drosophila melanogaster genetics Genes, Homeobox Hela Cells metabolism Molecular Sequence Data Plasmids Regulatory Sequences, Nucleic Acid Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Transcription Factors genetics Transfection FBrf0053392 92034991 1934068 1991 12 26 1991 12 26 2000 12 18

0092-8674 67 4 1991 Nov 15 Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. 701-16 We have conducted a genetic screen for mutations that decrease the effectiveness of signaling by a protein tyrosine kinase, the product of the Drosophila melanogaster sevenless gene. These mutations define seven genes whose wild-type products may be required for signaling by sevenless. Four of the seven genes also appear to be essential for signaling by a second protein tyrosine kinase, the product of the Ellipse gene. The putative products of two of these seven genes have been identified. One encodes a ras protein. The other locus encodes a protein that is homologous to the S. cerevisiae CDC25 protein, an activator of guanine nucleotide exchange by ras proteins. These results suggest that the stimulation of ras protein activity is a key element in the signaling by sevenless and Ellipse and that this stimulation may be achieved by activating the exchange of GTP for bound GDP by the ras protein. Howard Hughes Medical Institute, University of California, Berkeley 94720. Simon M A MA Bowtell D D DD Dodson G S GS Laverty T R TR Rubin G M GM eng GENBANK M77501 M80539 S60911 S60914 S60917 S60919 S60920 S60969 S61522 S61524 Journal Article

UNITED STATES Cell 0413066 0 Eye Proteins 0 Guanine Nucleotide Exchange Factors 0 Membrane Glycoproteins 0 Proteins 0 ras Guanine Nucleotide Exchange Factors 0 sevenless protein EC 2.7.1.112 Protein-Tyrosine Kinase EC 3.6.1.- GTP-Binding Proteins EC 3.6.1.- Proto-Oncogene Protein p21(ras) IM Amino Acid Sequence Comparative Study DNA Mutational Analysis Eye Proteins physiology GTP-Binding Proteins physiology Genes, Structural Guanine Nucleotide Exchange Factors Membrane Glycoproteins physiology Molecular Sequence Data Photoreceptors physiology Protein-Tyrosine Kinase physiology Proteins physiology Proto-Oncogene Protein p21(ras) physiology Restriction Mapping Saccharomyces cerevisiae genetics Schizosaccharomyces genetics Sequence Alignment Signal Transduction Structure-Activity Relationship Support, Non-U.S. Gov't ras Guanine Nucleotide Exchange Factors FBrf0055573 93046660 1423618 1992 12 11 1992 12 11 2000 12 18

0092-8674 71 4 1992 Nov 13 cactus, a gene involved in dorsoventral pattern formation of Drosophila, is related to the I kappa B gene family of vertebrates. 613-21 Among the maternally active genes of Drosophila, cactus is the only one whose loss of function mutations specifically produce ventralized embryos. Its product inhibits nuclear translocation of the dorsal morphogen in the dorsal region of the embryo. Here we report the cloning of cactus and the sequencing of its maternal transcript. The identity of our clones was verified by induction of phenocopies with antisense RNA and rescue of the mutant phenotype with sense RNA. cactus is predicted to encode an acidic, cytoplasmic protein with seven ankyrin repeats. The sequence has similarity to the I kappa B proteins that inhibit the vertebrate transcription factor NF-kappa B. In analogy to results obtained with I kappa B and NF-kappa B, bacterially expressed cactus protein can inhibit DNA binding of dorsal protein in vitro. Max-Planck-Institut für Entwicklungsbiologie, Abteilung Genetik, Tübingen, Germany. Geisler R R Bergmann A A Hiromi Y Y Nüsslein-Volhard C C eng GENBANK L04964 M97168 S47136 S47137 S47164 S47165 S47166 S47167 S47168 S72771 Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 Nuclear Proteins 0 Phosphoproteins 0 Proto-Oncogene Proteins 0 RNA, Antisense 0 dorsal protein, Drosophila 147337-75-5 relB protein 149059-01-8 cactus protein, Drosophila IM Amino Acid Sequence Animal Base Sequence Blotting, Northern Cloning, Molecular DNA-Binding Proteins chemistry genetics metabolism Drosophila melanogaster genetics Female Gene Expression Regulation drug effects Molecular Sequence Data Multigene Family genetics Nuclear Proteins metabolism Phosphoproteins chemistry genetics metabolism Proto-Oncogene Proteins genetics RNA, Antisense genetics pharmacology Restriction Mapping FBrf0123240 20059943 10591654 1999 12 23 1999 12 23 2001 11 02

0036-8075 286 5447 1999 Dec 10 Microarray analysis of Drosophila development during metamorphosis. 2179-84 Metamorphosis is an integrated set of developmental processes controlled by a transcriptional hierarchy that coordinates the action of hundreds of genes. In order to identify and analyze the expression of these genes, high-density DNA microarrays containing several thousand Drosophila melanogaster gene sequences were constructed. Many differentially expressed genes can be assigned to developmental pathways known to be active during metamorphosis, whereas others can be assigned to pathways not previously associated with metamorphosis. Additionally, many genes of unknown function were identified that may be involved in the control and execution of metamorphosis. The utility of this genome-based approach is demonstrated for studying a set of complex biological processes in a multicellular organism. Department of Developmental Biology, Beckman Center B300, Stanford University School of Medicine, Stanford, CA 94305-5329, USA. White K P KP Rifkin S A SA Hurban P P Hogness D S DS eng Journal Article

UNITED STATES Science 0404511 3604-87-3 Ecdysone IM Animal Apoptosis Cell Differentiation Central Nervous System cytology growth & development Drosophila melanogaster genetics growth & development metabolism Ecdysone Expressed Sequence Tags Gene Expression Gene Expression Profiling Gene Expression Regulation Genes, Insect Larva genetics growth & development Metamorphosis, Biological genetics Muscle Development Muscles cytology Oligonucleotide Array Sequence Analysis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0097690 97362023 9215559 1997 09 09 1997 09 09 2000 12 18

0009-5915 106 2 1997 Jul A framework physical map of Drosophila virilis based on P1 clones: applications in genome evolution. 99-107 The analysis of patterns of genome evolution may help to evaluate the evolutionary forces that shape the composition and organization of the genome. Comparisons between the physical maps of divergent species can be used to identify conserved blocks of closely linked genes whose synteny is possibly under selective constraint. We have used in situ hybridization to determine the genomic position of 732 randomly selected clones from a bacteriophage P1 library of Drosophila virilis. The resulting map includes at least one clone in each of 69% of the subdivisions into which the D. virilis polytene chromosomes are divided. A subset of these clones was used to carry out a comparative physical analysis of chromosome 2 from D. virilis and from Drosophila montana. A number of discrepancies with the classical scenario of chromosome evolution were noted. The D. virilis P1 clones were also used to determine the physical relations between ten genes that are located in the X chromosome of Drosophila melanogaster between the markers crn (2F1) and omb (4C5-6). In this region, which is approximately 2 Mb in length, there have been at least six breakpoints since the divergence of the species, and six of the genes are found at widely scattered locations in the D. virilis X chromosome. However, a block of four functionally unrelated genes, including white, roughest, Notch, and dunce, seems to be conserved between the two species. Department of Organismic and Evolutionary Biology, The Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. Vieira J J Vieira C P CP Hartl D L DL Lozovskaya E R ER eng Journal Article

GERMANY Chromosoma 2985138R IM Animal Bacteriophage P1 genetics Chromosome Mapping Comparative Study Drosophila genetics Evolution Genes, Insect Genome Genomic Library Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0099460 98043406 9383058 1998 02 05 1998 02 05 2003 08 29

0016-6731 147 3 1997 Nov Dominant enhancers of Egfr in Drosophila melanogaster: genetic links between the Notch and Egfr signaling pathways. 1139-53 The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context. Institute of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. jprice@sfu.ca Price J V JV Savenye E D ED Lum D D Breitkreutz A A eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Membrane Proteins 0 Repressor Proteins 0 notch protein 0 suppressor of Hairless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.10.- ERK-A protein IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase genetics metabolism Chromosome Mapping Drosophila melanogaster genetics Enhancer Elements (Genetics) Heterozygote Insect Proteins genetics metabolism Membrane Proteins metabolism Mutagenesis Phenotype Receptor, Epidermal Growth Factor genetics metabolism Repressor Proteins genetics metabolism Signal Transduction Support, Non-U.S. Gov't Wing growth & development FBrf0052091 91008451 2120155 1990 11 15 1990 11 15 2000 12 18

0018-067X 65 ( Pt 1) 1990 Aug Characterization of a novel Minute-locus in Drosophila melanogaster: a putative ribosomal protein gene. 51-7 We describe a novel Minute locus, M(1)7C, on the X-chromosome of Drosophila melanogaster. Heterozygous deficient females have most, if not all, of the Minute features (short and fine bristles, rough and somewhat larger eyes, thin-textured wings, missing aristae, affected antennae, delayed development, reduced fertility, and decreased viability). Both Minute and non-Minute adult progeny from Minute mothers suffer from Minute maternal effects such as abdominal segmentation defects, fused tergites, and missing or defective legs and halteres. Using a plasmid clone from region 7C5-9, which harbours the D. melanogaster ribosomal protein gene RPS14, we have found that the accumulation of a single transcript of approximately 650 b is extremely reduced in Minute larvae in comparison with wild-type. We have localized the RPS14 gene to approximately 28 kbp distal from the singed locus. The results suggest that M(1)7C and RPS14 may be the same gene. Department of Genetics, University of Umeå, Sweden. Andersson S S Lambertsson A A eng Journal Article

ENGLAND Heredity 0373007 0 RNA, Messenger 0 Ribosomal Proteins IM Animal Blotting, Southern Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics growth & development Female Heterozygote Male Mutation Phenotype RNA, Messenger biosynthesis Ribosomal Proteins genetics Support, Non-U.S. Gov't Survival X Chromosome FBrf0135707 21198207 11301250 2001 04 13 2001 06 28 2003 06 16

0960-9822 11 6 2001 Mar 20 A primary role for the epidermal growth factor receptor in ommatidial spacing in the Drosophila eye. 396-404 BACKGROUND: The differentiation of regularly spaced structures within an epithelium is a common feature of developmental pattern formation. The regular spacing of ommatidia in the Drosophila eye imaginal disc provides a good model for this phenomenon. The correct spacing of ommatidia is a central event in establishing the precise hexagonal pattern of ommatidia in the Drosophila compound eye. The R8 photoreceptors are the founder cells of each of the ommatidia that comprise the adult eye and are specified by a bHLH transcription factor, Atonal. RESULTS: We find that the epidermal growth factor receptor (Egfr) has a primary function in regulating R8 spacing. The receptor's activation within nascent ommatidia induces the expression of a secreted inhibitor that blocks atonal expression, and therefore ommatidial initiation, in nearby cells. The identity of the secreted inhibitor remains elusive but, contrary to previous suggestions, we show that it is not Argos. This Egfr-dependent inhibition acts in parallel to the inhibition of atonal by the secreted protein Scabrous. The activation of the Egfr pathway is dependent on Atonal function via the expression of Rhomboid-1. Our results also allow us to conclude that Egfr's role in promoting cell survival is largely independent of its role in photoreceptor recruitment; even when cell death is blocked, most photoreceptors fail to form. CONCLUSIONS: Based on our data and those of others, we propose a model for R8 spacing that comprises a self-organizing network of signaling molecules. This model describes how successive rows of ommatidia form out of phase with each other, leading to the hexagonal array of facets in the compound eye. MRC Laboratory of Molecular Biology, CB2 2QH, Cambridge, United Kingdom. Baonza A A Casci T T Freeman M M eng Journal Article

England Curr Biol 9107782 0 DNA-Binding Proteins 0 Eye Proteins 0 Glycoproteins 0 Insect Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Rho protein, Drosophila 0 ato protein 0 rho-2 protein, Drosophila 133925-66-3 scabrous protein, Drosophila 147954-53-8 gil protein EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Mitogen-Activated Protein Kinases IM Animal DNA-Binding Proteins metabolism Drosophila melanogaster Enzyme Activation Eye growth & development metabolism Eye Proteins metabolism Gene Expression Glycoproteins metabolism Helix-Loop-Helix Motifs Insect Proteins metabolism Membrane Proteins genetics Mitogen-Activated Protein Kinases metabolism Nerve Tissue Proteins metabolism Photoreceptors, Invertebrate metabolism Receptor, Epidermal Growth Factor genetics metabolism physiology Signal Transduction Support, Non-U.S. Gov't FBrf0155813 22474229 12586708 2003 02 14 2003 09 12

0016-6731 163 1 2003 Jan Analysis of Ras-induced overproliferation in Drosophila hemocytes. 203-15 We use the Drosophila melanogaster larval hematopoietic system as an in vivo model for the genetic and functional genomic analysis of oncogenic cell overproliferation. Ras regulates cell proliferation and differentiation in multicellular eukaryotes. To further elucidate the role of activated Ras in cell overproliferation, we generated a collagen promoter-Gal4 strain to overexpress Ras(V12) in Drosophila hemocytes. Activated Ras causes a dramatic increase in the number of circulating larval hemocytes (blood cells), which is caused by cellular overproliferation. This phenotype is mediated by the Raf/MAPK pathway. The mutant hemocytes retain the ability to phagocytose bacteria as well as to differentiate into lamellocytes. Microarray analysis of hemocytes overexpressing Ras(V12) vs. Ras(+) identified 279 transcripts that are differentially expressed threefold or more in hemocytes expressing activated Ras. This work demonstrates that it will be feasible to combine genetic and functional genomic approaches in the Drosophila hematopoietic system to systematically identify oncogene-specific downstream targets. Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. Asha H H Nagy Istvan I Kovacs Gabor G Stetson Daniel D Ando Istvan I Dearolf Charles R CR eng Journal Article

United States Genetics 0374636 EC 3.6.1.- ras Proteins IM Animal Cell Division genetics physiology Drosophila genetics metabolism Hemocytes metabolism Oligonucleotide Array Sequence Analysis Promoter Regions (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. ras Proteins genetics metabolism FBrf0088256 96202318 8643671 1996 07 17 1996 07 17 2000 12 18

0027-8424 93 4 1996 Feb 20 Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development. 1560-5 Several human neurological disorders are associated with proteins containing abnormally long runs of glutamine residues. Strikingly, most of these proteins contain two or more additional long runs of amino acids other than glutamine. We screened the current human, mouse, Drosophila, yeast, and Escherichia coli protein sequence data bases and identified all proteins containing multiple long homopeptides. This search found multiple long homopeptides in about 12% of Drosophila proteins but in only about 1.7% of human, mouse, and yeast proteins and none among E. coli proteins. Most of these sequences show other unusual sequence features, including multiple charge clusters and excessive counts of homopeptides of length > or = two amino acid residues. Intriguingly, a large majority of the identified Drosophila proteins are essential developmental proteins and, in particular, most play a role in central nervous system development. Almost half of the human and mouse proteins identified are homeotic homologs. The role of long homopeptides in fine-tuning protein conformation for multiple functional activities is discussed. The relative contributions of strand slippage and of dynamic mutation are also addressed. Several new experiments are proposed. Department of Mathematics, Stanford University, CA 94305-2125, USA. Karlin S S Burge C C eng GENBANK P04632 P07199 P10275 P10323 P10645 P11161 P14314 P14651 P14866 P17483 P18146 P19338 P20042 P20265 P20396 P22670 P23327 P23610 P25440 P25490 P32242 P35568 P41225 P42858 Q01851 Q03052 Q05925 Q06481 Q06945 S46268 2R01GM10452-31 GM NIGMS 5R01HG00335-07 HG NHGRI Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Homeodomain Proteins 0 Transcription Factors IM Amino Acid Sequence Animal Base Sequence Comparative Study Drosophila melanogaster genetics Escherichia coli genetics Genes, Homeobox Genes, Structural Homeodomain Proteins chemistry genetics Human Mice genetics Mice, Neurologic Mutants Molecular Sequence Data Multigene Family Nervous System embryology growth & development Nervous System Diseases genetics Saccharomyces cerevisiae genetics Species Specificity Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors chemistry genetics Trinucleotide Repeats FBrf0092657 97178963 9053304 1997 03 13 1997 03 13 2002 11 01

0950-1991 124 2 1997 Jan Induction of Drosophila eye development by decapentaplegic. 271-8 The Drosophila decapentaplegic (dpp) gene, encoding a secreted protein of the transforming growth factor-beta (TGF-beta) superfamily, controls proliferation and patterning in diverse tissues, including the eye imaginal disc. Pattern formation in this tissue is initiated at the posterior edge and moves anteriorly as a wave; the front of this wave is called the morphogenetic furrow (MF). Dpp is required for proliferation and initiation of pattern formation at the posterior edge of the eye disc. It has also been suggested that Dpp is the principal mediator of Hedgehog function in driving progression of the MF across the disc. In this paper, ectopic Dpp expression is shown to be sufficient to induce a duplicated eye disc with normal shape, MF progression, neuronal cluster formation and direction of axon outgrowth. Induction of ectopic eye development occurs preferentially along the anterior margin of the eye disc. Ectopic Dpp clones situated away from the margins induce neither proliferation nor patterning. The Dpp signalling pathway is shown to be under tight transcriptional and post-transcriptional control within different spatial domains in the developing eye disc. In addition, Dpp positively controls its own expression and suppresses wingless transcription. In contrast to the wing disc, Dpp does not appear to be the principal mediator of Hedgehog function in the eye. Howard Hughes Medical Institute, The School of Medicine, University of California, Los Angeles 90095, USA. Pignoni F F Zipursky S L SL eng Journal Article

ENGLAND Development 8701744 0 Actins 0 Antigens, CD2 0 Fungal Proteins 0 GAL4 protein, S cerevisiae 0 Insect Proteins 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Actins biosynthesis genetics Animal Animals, Genetically Modified Antigens, CD2 biosynthesis genetics Cell Differentiation Cell Division Crosses, Genetic Drosophila melanogaster growth & development Eye cytology growth & development Female Fungal Proteins biosynthesis genetics Gene Expression Regulation, Developmental Genotype Insect Proteins biosynthesis physiology Male Support, U.S. Gov't, P.H.S. Transforming Growth Factor beta physiology FBrf0138491 21405999 11514618 2001 08 21 2002 01 31 2002 04 19

1059-1524 12 8 2001 Aug Biogenesis of Golgi stacks in imaginal discs of Drosophila melanogaster. 2308-27 We provide a detailed description of Golgi stack biogenesis that takes place in vivo during one of the morphogenetic events in the lifespan of Drosophila melanogaster. In early third-instar larvae, small clusters consisting mostly of vesicles and tubules were present in epithelial imaginal disk cells. As larvae progressed through mid- and late-third instar, these larval clusters became larger but also increasingly formed cisternae, some of which were stacked. In white pupae, the typical Golgi stack was observed. We show that larval clusters are Golgi stack precursors by 1) localizing various Golgi-specific markers to the larval clusters by electron and immunofluorescence confocal microscopy, 2) driving this conversion in wild-type larvae incubated at 37 degrees C for 2 h, and 3) showing that this conversion does not take place in an NSF1 mutant (comt 17). The biological significance of this conversion became clear when we found that the steroid hormone 20-hydroxyecdysone (ecdysone) is critically involved in this conversion. In its absence, Golgi stack biogenesis did not occur and the larval clusters remained unaltered. We showed that dGM130 and sec23p expression increases approximately three- and fivefold, respectively, when discs are exposed to ecdysone in vivo and in vitro. Taken together, these results suggest that we have developed an in vivo system to study the ecdysone-triggered Golgi stack biogenesis. The Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh, EH9 3JR, Scotland, United Kingdom. Kondylis V V Goulding S E SE Dunne J C JC Rabouille C C eng Journal Article

United States Mol Biol Cell 9201390 0 Carrier Proteins 0 Drosophila Proteins 0 Golgi matrix protein, 130 kDa 0 Membrane Proteins 0 N-ethylmaleimide-sensitive protein 0 Phosphoproteins 0 Recombinant Fusion Proteins 0 Sec31 protein 0 Tissue Extracts 3604-87-3 Ecdysone EC 2.4.- fringe protein EC 2.4.1.- N-Acetylglucosaminyltransferases IM Animal Animals, Genetically Modified Carrier Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster growth & development physiology ultrastructure Ecdysone genetics pharmacology Female Golgi Apparatus chemistry drug effects physiology ultrastructure Human Immunoblotting Larva growth & development physiology ultrastructure Male Membrane Proteins metabolism Microscopy, Fluorescence Morphogenesis N-Acetylglucosaminyltransferases metabolism Phosphoproteins genetics metabolism Recombinant Fusion Proteins metabolism Support, Non-U.S. Gov't Tissue Extracts chemistry FBrf0083410 94338686 8060613 1994 09 22 1994 09 22 2000 12 18

0896-6273 13 2 1994 Aug Mutations affecting the pattern of the PNS in Drosophila reveal novel aspects of neuronal development. 269-87 Through a systematic genetic screen, we have identified 55 mutations that affect the development of the PNS of Drosophila embryos. These mutations specify 13 novel and 5 previously characterized genes and define new phenotypes for 2 other known genes. Five classes of mutant phenotypes were identified in the screen: gain of neurons, loss of neurons, abnormal position of chordotonal neurons, aberrant neuronal trajectories, and abnormal morphology of neurons. Phenotypic analyses of mutations identified in this study revealed three novel aspects of PNS development. First, we have identified a novel gene that may be required to define glial versus neuronal cell identity. Second, our data indicate that neuronal migration plays an important role in pattern formation in the embryonic PNS. Third, we have identified mutations that cause a lack of sensory organs, but unlike mutations in proneural genes, do not affect the formation of sensory organ precursors. These genes may be required for key aspects of neuronal differentiation. Our studies suggest that approximately 70 essential genes are required for proper PNS development in Drosophila embryos. Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030. Salzberg A A D'Evelyn D D Schulze K L KL Lee J K JK Strumpf D D Tsai L L Bellen H J HJ eng Journal Article

UNITED STATES Neuron 8809320 0 Antibodies, Monoclonal IM Dl abd-A cycA ded dmt dtl hrt iab-2 jay misn neu pav pros rho sens spdo stich1 stich2 ttk ut wan Animal Antibodies, Monoclonal Chromosome Mapping Drosophila melanogaster embryology genetics Mutagenesis Neurons cytology Peripheral Nervous System embryology Support, Non-U.S. Gov't FBrf0105197 99029841 9814704 1998 12 07 1998 12 07 2003 02 03

0092-8674 95 3 1998 Oct 30 The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. 331-41 Extracellular growth factors are required for the survival of most animal cells. They often signal through the activation of the Ras pathway. However, the molecular mechanisms by which Ras signaling inhibits the intrinsic cell death machinery are not well understood. Here, we present evidence that in Drosophila, activation of the Ras pathway specifically inhibits the proapoptotic activity of the gene head involution defective (hid). By using transgenic animals and cultured cells, we show that MAPK phosphorylation sites in Hid are critical for this response. These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene. Massachusetts Institute of Technology, Howard Hughes Medical Institute, Department of Biology, Cambridge 02139, USA. Bergmann A A Agapite J J McCall K K Steller H H eng Journal Article

UNITED STATES Cell 0413066 0 Insect Proteins 0 Neuropeptides 0 Peptides 0 grim protein, Drosophila 0 head involution defective protein 0 reaper peptide, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 2.7.10.- ERK-A protein EC 3.6.1.- ras Proteins IM Cell. 1998 Oct 30;95(3):295-8 9814699 Animal Animals, Genetically Modified Apoptosis Ca(2+)-Calmodulin Dependent Protein Kinase genetics metabolism Cell Line Cell Survival Drosophila melanogaster cytology genetics metabolism Eye cytology Genes, Lethal Genes, Suppressor Insect Proteins genetics metabolism Mutation Neuropeptides antagonists & inhibitors genetics metabolism Peptides genetics Phenotype Phosphorylation Proto-Oncogene Proteins c-raf genetics metabolism Receptor, Epidermal Growth Factor genetics metabolism Signal Transduction Support, Non-U.S. Gov't Transfection ras Proteins genetics metabolism FBrf0141438 21553061 11696329 2001 11 06 2002 01 22 2003 06 16

0960-9822 11 21 2001 Oct 30 Identification of the first invertebrate interleukin JAK/STAT receptor, the Drosophila gene domeless. 1700-5 The JAK/STAT signaling pathway plays important roles in vertebrate development and the regulation of complex cellular processes. Components of the pathway are conserved in Dictyostelium, Caenorhabditis, and Drosophila, yet the complete sequencing and annotation of the D. melanogaster and C. elegans genomes has failed to identify a receptor, raising the possibility that an alternative type of receptor exists for the invertebrate JAK/STAT pathway. Here we show that domeless (dome) codes for a transmembrane protein required for all JAK/STAT functions in the Drosophila embryo. This includes its known requirement for embryonic segmentation and a newly discovered function in trachea specification. The DOME protein has a similar extracellular structure to the vertebrate cytokine class I receptors, although its sequence has greatly diverged. Like many interleukin receptors, DOME has a cytokine binding homology module (CBM) and three extracellular fibronectin-type-III domains (FnIII). Despite its low degree of overall similarity, key amino acids required for signaling in the vertebrate cytokine class I receptors [3] are conserved in the CBM region. DOME is a signal-transducing receptor with most similarities to the IL-6 receptor family, but it also has characteristics found in the IL-3 receptor family. This suggests that the vertebrate families evolved from a single ancestral receptor that also gave rise to dome. Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, United Kingdom. Brown S S Hu N N Hombría J C JC eng Journal Article

England Curr Biol 9107782 0 Drosophila Proteins 0 Receptors, Interleukin 0 domeless protein, Drosophila IM Amino Acid Motifs Amino Acid Sequence Animal Comparative Study Drosophila embryology Drosophila Proteins genetics isolation & purification Evolution, Molecular Genes, Insect Molecular Sequence Data Receptors, Interleukin genetics isolation & purification Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Trachea embryology FBrf0074350 94340823 8062457 1994 09 22 1994 09 22 2002 11 01

0192-253X 15 3 1994 Sex determination in Drosophila melanogaster: X-linked genes involved in the initial step of sex-lethal activation. 251-64 Sex determination is the commitment of an embryo to either the female or the male developmental pathway. The ratio of X chromosomes to sets of autosomes is the primary genetic signal that determines sex in Drosophila, by triggering the functional state of the gene Sex-lethal: in females (2X;2A) Sxl will be ON, whereas in males (X;2A) Sxl will be OFF. Genetic and molecular studies have defined a set of genes involved in the formation of the X:A signal, as well as other genes, with either maternal or zygotic effects, which are also involved in regulating the initial step of Sex-lethal activation. We review these data and present new data on two more regions of the X chromosome that define other genes needed for Sxl activation. In addition, we report on the interaction between some of the genes regulating Sxl activation. Centro de Investigaciones Biológicas, Velázquez, Madrid, Spain. Sánchez L L Granadino B B Torres M M eng Journal Article

UNITED STATES Dev Genet 7909963 0 DNA-Binding Proteins 0 Insect Hormones 0 Runt protein 0 Sxl protein, Drosophila 0 Transcription Factors 0 sisterless-a protein IM Sxl run sis-a Animal DNA-Binding Proteins genetics Dosage Compensation (Genetics) Drosophila melanogaster genetics Female Genes, Lethal Insect Hormones genetics Linkage (Genetics) Male Sex Differentiation genetics Support, Non-U.S. Gov't Transcription Factors genetics X Chromosome FBrf0088118 96391174 8798147 1997 02 05 1997 02 05 2003 06 16

0925-4773 56 1-2 1996 May Expression patterns of developmental genes reveal segment and parasegment organization of D. melanogaster genital discs. 61-72 We have used the expression patterns of genes known to be important during early Drosophila development to determine the segment-parasegment organization of the genital discs and to localize the three primordia in the male and female genital discs, engrailed (en) and hedgehog (hh) were used to locate posterior compartments in A8-A10, while cubitus interrupts (ci) localized the anterior compartments for each segment, decapentaplegic (dpp) identified the anterior cells that abut en and hh at the anterior-posterior border. abdominal-A (abd-A) identified the anterior compartment for abdominal segment 8 (aA8) in females but was not detected in the repressed female primordium in male discs. Abdominal-B (Abd-B) was expressed throughout the discs except for a small area along the edge of the posterior lobes, leaving open the possibility that A11 may contribute to the genital discs, caudal (cad) was expressed segmentally in the anal primordium of A10, extending through the Abd-B unstained region, wingless (wg) and gooseberry (gsb) may have assumed an added role in the discs perhaps providing proximal-distal cues. Models are presented to show how the segments and parasegments may fuse together during embryogenesis to form the mature male and female genital discs. Department of Biology, University of Central Florida, Orlando 32816, USA. Freeland D E DE Kuhn D T DT eng Journal Article

IRELAND Mech Dev 9101218 0 Abd-B proteins, Drosophila 0 CAD multifunctional protein 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Hormones 0 Insect Proteins 0 Multienzyme Complexes 0 Proto-Oncogene Proteins 0 Transcription Factors 0 cubitus interruptus protein 0 dpp protein, Drosophila 0 engrail protein, Drosophila 117758-26-6 wingless protein, Drosophila 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 2.1.3.2 Aspartate Carbamoyltransferase EC 3.5.2.3 Dihydroorotase EC 6.3.5.5 Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) IM Animal Aspartate Carbamoyltransferase physiology Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) physiology DNA-Binding Proteins physiology Dihydroorotase physiology Drosophila melanogaster embryology genetics Female Gene Expression Regulation, Developmental Genes, Structural, Insect Genitalia embryology metabolism Homeodomain Proteins physiology Insect Hormones physiology Insect Proteins physiology Male Morphogenesis genetics Multienzyme Complexes physiology Proto-Oncogene Proteins physiology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription Factors physiology FBrf0074680 94325602 8049466 1994 09 08 1994 09 08 2000 12 18

1993 Cell patterning in the Drosophila segment: engrailed and wingless antigen distributions in segment polarity mutant embryos. 105-14 By a complex and little understood mechanism, segment polarity genes control patterning in each segment of the Drosophila embryo. During this process, cell to cell communication plays a pivotal role and is under direct control of the products of segment polarity genes. Many of the cloned segment polarity genes have been found to be highly conserved in evolution, providing a model system for cellular interactions in other organisms. In Drosophila, two of these genes, engrailed and wingless, are expressed on either side of the parasegment border. wingless encodes a secreted molecule and engrailed a nuclear protein with a homeobox. Maintenance of engrailed expression is dependent on wingless and vice versa. To investigate the role of other segment polarity genes in the mutual control between these two genes, we have examined wingless and engrailed protein distribution in embryos mutant for each of the segment polarity genes. In embryos mutant for armadillo, dishevelled and porcupine, the changes in engrailed expression are identical to those in wingless mutant embryos, suggesting that their gene products act in the wingless pathway. In embryos mutant for hedgehog, fused, cubitus interruptus Dominant and gooseberry, expression of engrailed is affected to varying degrees. However wingless expression in the latter group decays in a similar way earlier than engrailed expression, indicating that these gene products might function in the maintenance of wingless expression. Using double mutant embryos, epistatic relationships between some segment polarity genes have been established. We present a model showing a current view of segment polarity gene interactions. Howard Hughes Medical Institute, Stanford, CA. van den Heuvel M M Klingensmith J J Perrimon N N Nusse R R eng Journal Article Review Review, Tutorial

ENGLAND Dev Suppl 9113706 0 Insect Hormones 0 Proto-Oncogene Proteins 0 Transcription Factors 0 engrail protein, Drosophila 117758-26-6 wingless protein, Drosophila IM en wg Animal Drosophila melanogaster embryology Genes, Structural, Insect physiology Insect Hormones physiology Morphogenesis genetics Mutation genetics Proto-Oncogene Proteins physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors physiology 53 FBrf0091161 97134673 8980233 1997 02 03 1997 02 03 2002 12 26

0092-8674 87 7 1996 Dec 27 TAF(II)s mediate activation of transcription in the Drosophila embryo. 1271-84 Mutations in the genes for two highly conserved TAFs, TAF(II)60 and TAF(II)110, reduce transcription of Bicoid-dependent target genes in vivo. By means of several distinct genetic test systems, specific activator-TAF interactions are shown to support both simple and synergistic enhancement of transcription in the embryo. These studies provide in vivo evidence that TAFs can serve as coactivators to receive gene-specific transcriptional activation signals. This genetic system also presents the opportunity to study the function of basal transcription components in regulating development of complex organisms. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA. Sauer F F Wassarman D A DA Rubin G M GM Tjian R R eng GENBANK U73125 Journal Article Retracted Publication

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 Insect Hormones 0 Insect Proteins 0 Macromolecular Systems 0 RNA, Messenger 0 TAFII60 protein 0 Taf110 protein, Drosophila 0 Trans-Activators 0 Transcription Factor TFIID 0 Transcription Factors 0 bicoid protein, Drosophila IM Sauer F, Wassarman DA, Rubin GM, Tjian R. Cell 1998 Nov 13; 95(4):following 573 Alleles Animal Base Sequence Body Patterning DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Eye embryology Gene Expression Regulation, Developmental In Situ Hybridization Insect Hormones genetics Insect Proteins genetics Macromolecular Systems Molecular Sequence Data RNA, Messenger genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators genetics Transcription Factor TFIID Transcription Factors chemistry genetics Transcription, Genetic FBrf0046969 88038810 3118188 1987 12 04 1987 12 04 2000 12 18

0270-7306 7 8 1987 Aug Structure and ligand specificity of the Drosophila melanogaster insulin receptor. 2718-27 The insulin-binding and protein tyrosine kinase subunits of the Drosophila melanogaster insulin receptor homolog have been identified and characterized by using antipeptide antibodies elicited to the deduced amino acid sequence of the alpha and beta subunits of the human insulin receptor. In D. melanogaster embryos and cell lines, the insulin receptor contains insulin-binding alpha subunits of 110 or 120 kilodaltons (kDa), a 95-kDa beta subunit that is phosphorylated on tyrosine in response to insulin in intact cells and in vitro, and a 170-kDa protein that may be an incompletely processed receptor. All of the components are synthesized from a proreceptor, joined by disulfide bonds, and exposed on the cell surface. The beta subunit is recognized by an antipeptide antibody elicited to amino acids 1142 to 1162 of the human insulin proreceptor, and the alpha subunit is recognized by an antipeptide antibody elicited to amino acids 702 to 723 of the human proreceptor. Of the polypeptide ligands tested, only insulin reacts with the D. melanogaster receptor. Insulinlike growth factors type I and II, epidermal growth factor, and the silkworm insulinlike prothoracicotropic hormone are unable to stimulate autophosphorylation. Thus despite the evolutionary divergence of vertebrates and invertebrates, the essential features of the structure and intrinsic functions of the insulin receptor have been remarkably conserved. Memorial Sloan-Kettering Cancer Center, New York, New York. Fernandez-Almonacid R R Rosen O M OM eng AM35158 AM NIADDK GM34555 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Amino Acids 0 Antibodies 0 Antigen-Antibody Complex 0 Ligands 0 Macromolecular Systems EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Insulin IM Amino Acids analysis Animal Antibodies Antigen-Antibody Complex Cell Line Cell Membrane metabolism Comparative Study Drosophila melanogaster metabolism Human Ligands Macromolecular Systems Molecular Weight Phosphorylation Protein-Tyrosine Kinase metabolism Receptor, Insulin metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0109903 99339924 10409512 1999 10 08 1999 10 08 2001 11 02

0950-1991 126 16 1999 Aug Cubitus interruptus is necessary but not sufficient for direct activation of a wing-specific decapentaplegic enhancer. 3669-77 In Drosophila, the imaginal discs are the primordia for adult appendages. Their proper formation is dependent upon the activation of the decapentaplegic (dpp) gene in a stripe of cells just anterior to the compartment boundary. In imaginal discs, the dpp gene has been shown to be activated by Hedgehog signal transduction. However, an initial analysis of its enhancer region suggests that its regulation is complex and depends upon additional factors. In order to understand how multiple factors regulate dpp expression, we chose to focus on a single dpp enhancer element, the dpp heldout enhancer, from the 3' cis regulatory disc region of the dpp locus. In this report, we present a molecular analysis of this 358 bp wing- and haltere-specific dpp enhancer, which demonstrates a direct transcriptional requirement for the Cubitus interruptus (Ci) protein. The results suggest that, in addition to regulation by Ci, expression of the dpp heldout enhancer is spatially determined by Drosophila TCF (dTCF) and the Vestigial/Scalloped selector system and that temporal control is provided by dpp autoregulation. Consistent with the unexpectedly complex regulation of the dpp heldout enhancer, analysis of a Ci consensus site reporter construct suggests that Ci, a mediator of Hedgehog transcriptional activation, can only transactivate in concert with other factors. Department of Biochemistry, Molecular Biology and Cell Biology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA. Hepker J J Blackman R K RK Holmgren R R eng GM57450 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Transforming Growth Factor beta 0 cubitus interruptus protein 0 dpp protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 3.2.1.23 beta-Galactosidase IM Animal Animals, Genetically Modified Base Sequence Consensus Sequence DNA-Binding Proteins genetics metabolism Drosophila melanogaster genetics growth & development Enhancer Elements (Genetics) Gene Expression Regulation, Developmental Genes, Reporter Insect Proteins genetics Larva Molecular Sequence Data Proto-Oncogene Proteins physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Transforming Growth Factor beta metabolism Translation, Genetic Wing Zinc Fingers beta-Galactosidase genetics FBrf0074069 95236986 7720561 1995 05 25 1995 05 25 2000 12 18

0950-1991 120 11 1994 Nov Function of Drosophila ovo+ in germ-line sex determination depends on X-chromosome number. 3185-95 Germ-line sex determination in Drosophila melanogaster requires an assessment of the number of X chromosomes as measured against autosomal standards (XX = female, X = male) and signaling from the soma. Both of these sex determination cues are required for female-specific Sex-lethal+ function in germ cells. The ovo+ locus encodes zinc finger protein(s) required for female-specific splicing of Sex-lethal+ pre-mRNA, making ovo+ a candidate function acting between the two principal cues and Sex-lethal+. We have made ovo reporter genes and find that they show high activity in the germ line of females and low activity in the germ line of males. XY flies transformed into somatic females do not show high levels of reporter activity, while XX flies transformed into somatic males do. This shows that high level ovo+ expression depends on the number of X chromosomes, not the somatic sexual signals. The requirement for ovo+ function is restricted to XX flies. Mutations in ovo have no effect on XY males, X0 males or XY females, but have pronounced effects on germ cell viability in XX females, XX females with sex transformed germ lines, and XX males indicating that ovo+ gene products are required for events occurring only in flies with two X chromosomes. Laboratory of Developmental Genetics and Physiology, CNRS Case 907, University of Marseille, France. Oliver B B Singer J J Laget V V Pennetta G G Pauli D D eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Transcription Factors 0 ovo protein IM ovo Animal Chromosome Mapping DNA-Binding Proteins genetics Drosophila melanogaster genetics Female Gene Expression Genes, Insect physiology Human Male Models, Biological Ovary physiology Sex Determination (Analysis) Support, Non-U.S. Gov't Transcription Factors genetics X Chromosome FBrf0155665 22532484 12645932 2003 03 20 2003 04 09

0012-1606 253 2 2003 Jan 15 SNR1 is an essential subunit in a subset of Drosophila brm complexes, targeting specific functions during development. 291-308 The snr1 gene of Drosophila melanogaster encodes a conserved component of the multiprotein Brahma (Brm) complex, a counterpart to the SWI/SNF complexes that participate in ATP-dependent chromatin remodeling. Loss-of-function and null mutations in the snr1 gene reveal its essential role in Drosophila development. We identified new mutant alleles and ectopically expressed deleted forms to dissect the specific functions of SNR1. Somatic and germ cell clone analyses confirmed its requirement in a continuous and widespread fashion for proper cell fate determination and oogenesis. Expression of SNR1 transgenes revealed unexpected roles in wing patterning, abdomen development, oogenesis, and sustained adult viability. A widespread distribution of SNR1 and BRM on the salivary gland polytene chromosomes showed that the Brm complex associated with many genes, but not always at transcribed loci, consistent with genetic data suggesting roles in both gene activation and repression. Despite essential Brm complex functions in leg development, genetic and protein localization studies revealed that snr1 was not required or expressed in all tissues dependent on Brm complex activities. Thus, SNR1 is essential for some, but not all Brm functions, and it likely serves as an optional subunit, directing Brm complex activity to specific gene loci or cellular processes. Department of Biology, Syracuse University, Syracuse, NY 13244-1270, USA. Zraly Claudia B CB Marenda Daniel R DR Nanchal Runjhun R Cavalli Giacomo G Muchardt Christian C Dingwall Andrew K AK eng Journal Article

United States Dev Biol 0372762 0 Cell Cycle Proteins 0 Drosophila Proteins 0 Protein Subunits 0 Snr1 protein 0 Trans-Activators 0 Transcription Factors 0 brahma protein IM Alleles Amino Acid Sequence Animal Animals, Genetically Modified Cell Cycle Proteins chemistry genetics physiology Drosophila Proteins chemistry genetics physiology Drosophila melanogaster genetics growth & development physiology Female Gene Expression Regulation, Developmental Genes, Insect Male Molecular Sequence Data Mosaicism Mutation Phenotype Protein Subunits Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Trans-Activators chemistry genetics physiology Transcription Factors chemistry genetics physiology FBrf0054627 92102954 1684717 1992 02 07 1992 02 07 2000 12 18

0925-4773 35 2 1991 Sep Interactions between segment polarity genes and the generation of the segmental pattern in Drosophila. 77-87 Although mutations in the segment polarity genes wingless, engrailed, hedgehog, gooseberry and cubitus-interruptusD all affect the region of naked cuticle within each segment of the Drosophila larva, subtle phenotypic differences suggest that these genes play different roles in segmental patterning. In this paper, the regulative interactions between these genes are analysed. They have revealed that the products of most of these genes accomplish more than one function during embryogenesis. Whereas early on a positive feed-back loop involving wg, en and hh maintains the expression of wg and en in the extremes of each parasegment, later on wg and en become independent from each other. en appears to regulate the expression of hh and ptc, while wg depends on gsb and ciD. Imperial Cancer Research Fund, Department of Zoology, University of Oxford, U.K. Hidalgo A A eng Journal Article

IRELAND Mech Dev 9101218 IM ci<up>D</up> en eve gsb gsb-d hh nkd ptc wg Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Feedback Gene Expression Regulation Genes, Homeobox Genes, Regulator Larva ultrastructure Phenotype FBrf0103357 98356018 9691040 1998 09 28 1998 09 28 2000 12 18

0016-6731 149 4 1998 Aug Needs and targets for the multi sex combs gene product in Drosophila melanogaster. 1823-38 We have analyzed the requirements for the multi sex combs (mxc) gene during development to gain further insight into the mechanisms and developmental processes that depend on the important trans-regulators forming the Polycomb group (PcG) in Drosophila melanogaster. mxc is allelic with the tumor suppressor locus lethal (1) malignant blood neoplasm (l(1)mbn). We show that the mxc product is dramatically needed in most tissues because its loss leads to cell death after a few divisions. mxc has also a strong maternal effect. We find that hypomorphic mxc mutations enhance other PcG gene mutant phenotypes and cause ectopic expression of homeotic genes, confirming that PcG products are cooperatively involved in repression of selector genes outside their normal expression domains. We also demonstrate that the mxc product is needed for imaginal head specification, through regulation of the ANT-C gene Deformed. Our analysis reveals that mxc is involved in the maternal control of early zygotic gap gene expression previously reported for some PcG genes and suggests that the mechanism of this early PcG function could be different from the PcG-mediated regulation of homeotic selector genes later in development. We discuss these data in view of the numerous functions of PcG genes during development. Centre de Génétique Moléculaire du Centre National de la Recherche Scientifique, 91198 Gif Sur Yvette Cedex, France. Saget O O Forquignon F F Santamaria P P Randsholt N B NB eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 134549-01-2 Polycomb protein, insect IM Alleles Animal Drosophila melanogaster genetics growth & development immunology Female Gene Deletion Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Genes, MHC Class II Insect Proteins genetics Larva genetics growth & development Male Mutation Phenotype Support, Non-U.S. Gov't FBrf0068440 94139676 8306973 1994 03 16 1994 03 16 2000 12 18

0261-4189 13 1 1994 Jan 1 The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development. 71-82 The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a polypeptide of the transforming growth factor-beta family of secreted factors. It is required for the proper development of both embryonic and adult structures, and may act as a morphogen in the embryo. In wing imaginal discs, dpp is expressed and required in a stripe of cells near the anterior-posterior compartment boundary. Here we show that viable mutations in the segment polarity genes patched (ptc) and costal-2 (cos2) cause specific alterations in dpp expression within the anterior compartment of the wing imaginal disc. The interaction between ptc and dpp is particularly interesting; both genes are expressed with similar patterns at the anterior-posterior compartment boundary of the disc, and mis-expressed in a similar way in segment polarity mutant backgrounds like ptc and cos2. This mis-expression of dpp could be correlated with some of the features of the adult mutant phenotypes. We propose that ptc controls dpp expression in the imaginal discs, and that the restricted expression of dpp near the anterior-posterior compartment boundary is essential to maintain the wild-type morphology of the wing disc. Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain. Capdevila J J Estrada M P MP Sánchez-Herrero E E Guerrero I I eng Journal Article

ENGLAND EMBO J 8208664 0 Insect Hormones 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 9007-49-2 DNA IM cos2 dpp ptc Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA Drosophila embryology genetics Gene Expression Regulation Insect Hormones genetics Molecular Sequence Data Mutation Phenotype Promoter Regions (Genetics) Restriction Mapping Support, Non-U.S. Gov't Transforming Growth Factor beta genetics Wing embryology FBrf0054721 92079923 1745245 1992 01 15 1992 01 15 2000 12 18

0026-8925 230 1-2 1991 Nov Ribosomal protein S14 is not responsible for the Minute phenotype associated with the M(1)7C locus in Drosophila melanogaster. 8-11 A locus associated with a severe Minute effect has been mapped at 7C on the X chromosome of Drosophila melanogaster. Previous work has suggested that this Minute encodes ribosomal proteins S14A and S14B. We have made a chromosomal deficiency that removes the S14 ribosomal protein genes, yet does not display the Minute phenotype. These data suggest that the S14 genes do not actually correspond to the Minute locus. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107. Dorer D R DR Anane-Firempong A A Christensen A C AC eng GM38483 GM NIGMS Journal Article

GERMANY Mol Gen Genet 0125036 0 Ribosomal Proteins 0 ribosomal protein S14 9007-49-2 DNA IM Animal Chromosome Banding Chromosome Mapping Crosses, Genetic DNA genetics Drosophila melanogaster genetics Female Karyotyping Male Mutagenesis Nucleic Acid Hybridization Phenotype Ribosomal Proteins genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome FBrf0107641 99189751 10089881 1999 04 22 1999 04 22 2003 06 16

0092-8674 96 5 1999 Mar 5 Sprouty, an intracellular inhibitor of Ras signaling. 655-65 Sprouty was identified in a genetic screen as an inhibitor of Drosophila EGF receptor signaling. The Egfr triggers cell recruitment in the eye, and sprouty- eyes have excess photoreceptors, cone cells, and pigment cells. Sprouty's function is, however, more widespread. We show that it also interacts genetically with the receptor tyrosine kinases Torso and Sevenless, and it was first discovered through its effect on FGF receptor signaling. In contrast to an earlier proposal that Sprouty is extracellular, we show by biochemical analysis that Sprouty is an intracellular protein, associated with the inner surface of the plasma membrane. Sprouty binds to two intracellular components of the Ras pathway, Drk and Gap1. Our results indicate that Sprouty is a widespread inhibitor of Ras pathway signal transduction. MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. Casci T T Vinós J J Freeman M M eng Journal Article

UNITED STATES Cell 0413066 0 Eye Proteins 0 Insect Proteins 0 Macromolecular Systems 0 Membrane Glycoproteins 0 Membrane Proteins 0 Proteins 0 drk protein, Drosophila 0 rasGTPase-activating protein-1 0 sevenless protein 0 sprouty protein, Drosophila 52-90-4 Cysteine EC 2.7.1.- TOR protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 3.6.1.- ras Proteins IM Animal Cells, Cultured Cysteine chemistry Depression, Chemical Drosophila melanogaster embryology genetics growth & development physiology Eye cytology growth & development Eye Abnormalities genetics Eye Proteins physiology Insect Proteins genetics physiology Macromolecular Systems Membrane Glycoproteins physiology Membrane Proteins physiology Morphogenesis Proteins physiology Receptor Protein-Tyrosine Kinases physiology Receptor, Epidermal Growth Factor physiology Signal Transduction physiology Support, Non-U.S. Gov't ras Proteins physiology FBrf0049804 90108690 2575066 1990 02 22 1990 02 22 2002 11 08

0890-9369 3 9 1989 Sep The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain. 1424-36 In Drosophila the Abdominal-B (Abd-B) domain of the bithorax complex specifies the identities of several posterior abdominal segments, comprises homeo-protein-coding regions and cis-regulatory regions, and extends from infra-abdominal-5 (iab-5) to iab-8, inclusive. Mutations that eliminate the Abd-B domain act as late embryonic lethals and result in transformations of posterior abdominal segments toward more anterior ones. The Abd-B domain gives rise to a minimum of five homeo-box-containing transcripts, 7.8, 4.7, 4.3, 3.7, and 3.3 kb in length. We examined the structure of the Abd-B domain by sequencing two Abd-B cDNA clones derived from the 4.3- and the 4.7-kb transcripts and the corresponding genomic DNA. The domain spans approximately 100 kb and contains at least eight exons. The 4.7- and 4.3-kb transcripts contain an open reading frame capable of encoding a 54-kD protein. A portion of the deduced protein-coding sequence common to all of the Abd-B transcripts was cloned into an expression vector. The resultant fusion protein then was used to derive a monoclonal antibody specific to Abd-B. By use of that antibody, we identified two embryonic Abd-B proteins, 54 and 36 kD and determined the sum of their segmental distribution by immunohistochemical analysis of whole-mounted embryos and immunofluorescent analysis of dissected embryonic nervous systems. The proteins are distributed in the fourth to the ninth abdominal segments [parasegments (PS) 10-15] inclusive. Embryos homozygous for Polycomb (Pc) show labeling over almost the entire embryo, whereas embryos deficient for the Abd-B domain show no detectable labeling. Division of Biology, California Institute of Technology, Pasadena 91125. Celniker S E SE Keelan D J DJ Lewis E B EB eng GM-40499 GM NIGMS HD-06331 HD NICHD PR-07003 PHS Journal Article

UNITED STATES Genes Dev 8711660 0 Abd-B proteins, Drosophila 0 Insect Hormones 0 RNA, Messenger 0 Recombinant Fusion Proteins 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence DNA genetics Drosophila melanogaster embryology genetics Embryo and Fetal Development Embryo, Nonmammalian analysis Gene Expression Regulation Genes, Homeobox Human Insect Hormones analysis genetics Mice Molecular Sequence Data RNA, Messenger genetics Recombinant Fusion Proteins biosynthesis Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0090758 96427359 8830723 1996 11 04 1996 11 04 2003 06 16

0165-4608 90 2 1996 Sep Three mutant genes cooperatively induce brain tumor formation in Drosophila malignant brain tumor. 135-41 The Drosophila melanogaster strain Malignant Brain Tumor reveals temperature-sensitive transformation of the larval brain tissue. Genetic analysis shows that three gene defects, spzMBT, yetiMBT, and tldMBT, cooperatively induce brain tumor formation. Whereas spz and tld belong to the genes inducing differentiation patterns in the embryo, yeti induces cell overgrowth. spzMBT-, yetiMBT-, and tldMBT-containing animals are larval lethal, whereas Malignant Brain Tumor is kept as a homozygous strain at a permissive temperature. This reveals that this tumor-forming strain is the result of a number of adaptive mutation events. BL-Institut für Neurobiologie, Madgeburg, Germany. Riede I I eng Journal Article

UNITED STATES Cancer Genet Cytogenet 7909240 0 Genetic Markers 0 Insect Hormones 0 Proteins 0 spatzle protein, Drosophila 144714-21-6 tld protein, Drosophila IM Animal Brain Neoplasms genetics pathology Cell Differentiation Cell Transformation, Neoplastic Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics Embryo, Nonmammalian Female Genes, Insect Genes, Tumor Suppressor genetics Genetic Markers Genotype Insect Hormones genetics Larva Male Proteins genetics Recombination, Genetic Support, Non-U.S. Gov't Temperature FBrf0102315 98230240 9570314 1998 05 12 1998 05 12 2002 11 01

1355-8382 4 2 1998 Feb The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA. 142-50 Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm. Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany. Gebauer F F Merendino L L Hentze M W MW Valcárcel J J eng Journal Article

UNITED STATES RNA 9509184 0 RNA, Messenger 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 9007-49-2 DNA IM Animal Base Sequence Binding Sites genetics DNA genetics Drosophila melanogaster genetics metabolism Female Gene Expression Genes, Reporter Introns Male RNA Splicing genetics RNA, Messenger genetics metabolism RNA-Binding Proteins genetics Sex Differentiation genetics Support, Non-U.S. Gov't Translation, Genetic FBrf0100049 98070317 9405369 1998 02 19 1998 02 19 2002 11 01

0261-4189 16 24 1997 Dec 15 Synergistic activation of a Drosophila enhancer by HOM/EXD and DPP signaling. 7402-10 The homeotic proteins encoded by the genes of the Drosophila HOM and the vertebrate HOX complexes do not bind divergent DNA sequences with a high selectivity. In vitro, HOM (HOX) specificity can be increased by the formation of heterodimers with Extradenticle (EXD) or PBX homeodomain proteins. We have identified a single essential Labial (LAB)/EXD-binding site in a Decapentaplegic (DPP)-responsive enhancer of the homeotic gene lab which drives expression in the developing midgut. We show that LAB and EXD bind cooperatively to the site in vitro, and that the expression of the enhancer in vivo requires exd and lab function. In addition, point mutations in either the EXD or the LAB subsite compromise enhancer function, strongly suggesting that EXD and LAB bind to this site in vivo. Interestingly, we found that the activity of the enhancer is only stimulated by DPP signaling significantly upon binding of LAB and EXD. Thus, the enhancer appears to integrate positional information via the homeotic gene lab, and spatiotemporal information via DPP signaling; only when these inputs act in concert in an endodermal cell is the enhancer fully active. Our results illustrate how a tissue-specific response to DPP can be generated through synergistic effects on an enhancer carrying both DPP- and HOX-responsive sequences. Abteilung Zellbiologie, Biozentrum, Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Grieder N C NC Marty T T Ryoo H D HD Mann R S RS Affolter M M eng Journal Article

ENGLAND EMBO J 8208664 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 Recombinant Proteins 0 Transcription Factors 0 dpp protein, Drosophila 0 exd protein, Drosophila IM Animal Base Sequence DNA-Binding Proteins biosynthesis genetics metabolism Dimerization Drosophila melanogaster genetics Enhancer Elements (Genetics) Genes, Homeobox Genes, Insect Homeodomain Proteins biosynthesis Insect Proteins biosynthesis genetics metabolism Molecular Sequence Data Mutagenesis, Site-Directed Polymerase Chain Reaction Recombinant Proteins biosynthesis metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors biosynthesis genetics metabolism Vertebrates FBrf0051940 90337282 2116352 1990 09 12 1990 09 12 2000 12 18

0016-6731 125 2 1990 Jun Transvection in the Ultrabithorax domain of the bithorax complex of Drosophila melanogaster. 371-82 The phenotypes of several heterozygous combinations of mutations which map within the Ultrabithorax gene of Drosophila melanogaster are modulated by the extent of somatic homologous chromosome pairing, an effect known as transvection. One can discriminate between otherwise phenotypically similar mutations via their transvection behavior. This suggested the existence of previously undetected intragenic functional units. A collection of mutations has been classified into "transvection groups" (in analogy to complementation groups) on the basis of transvection tests with bithorax34e, postbithorax2, and Contrabithorax1 Ultrabithorax1. The conditions necessary for each transvection effect were determined from these transvection groups. The bithorax34e mutation only transvects with Ultrabithorax mutations with a contiguous Ultrabithorax transcriptional unit. In contrast, postbithorax2 transvection requires the distal part of the bithoraxoid region. As expected, Ultrabithorax mutations do not transvect with Contrabithorax1 Ultrabithorax1. However, it appears that this cross activation is not mediated solely through one of the known regulatory regions as mutations in these regions do not consistently block the response. Centro de Biologia Molecular del C.S.I.C., Facultad de Ciencias, Universidad Autónoma de Madrid, Spain. Mathog D D eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosomes physiology Drosophila melanogaster anatomy & histology genetics Gene Expression Regulation Genes Genetic Complementation Test Models, Genetic Mutation Phenotype Support, Non-U.S. Gov't FBrf0051949 91060075 2123163 1991 01 09 1991 01 09 2000 12 18

0016-6731 126 2 1990 Oct Genetic analysis of two female-sterile loci affecting eggshell integrity and embryonic pattern formation in Drosophila melanogaster. 427-34 We have analyzed female-sterile mutations at the X-linked loci fs(1)Nas and fs(1)ph which show allele-specific effects on egg shell structure and embryonic pattern formation. The majority of mutant alleles at both loci lead to a collapsed egg phenotype. The maternal effect lethal phenotype is characterized by cuticle defects resembling those found in three autosomal mutants of the terminal class. We have analyzed the complementation behavior of various heteroallelic combinations at both loci and show that one such combination at the fs(1)Nas locus is capable of restoring normal fertility. We have investigated possible interactions between fs(1)Nas and fs(1)ph and also between the terminal allele of fs(1)Nas and various maternal effect mutations altering the anteroposterior polarity of embryos. We have isolated one new allele of fs(1)Nas which combines the locus-typical phenotypic features with novel cuticle phenotypes. Our results suggest that the products of fs(1)Nas and fs(1)ph are required for the stability of the vitelline membrane and are also involved in a morphogenetic pathway necessary for the correct differentiation of the terminal regions of the embryo. Possible mechanisms to account for the association of these two functions are discussed. Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. Degelmann A A Hardy P A PA Mahowald A P AP eng HD-17607 HD NICHD HD-17608 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Drosophila melanogaster embryology genetics Female Genes Genetic Complementation Test Mutation Oocytes cytology Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0080369 95229058 7713429 1995 05 18 1995 05 18 2002 11 08

0016-6731 139 2 1995 Feb Drawing a stripe in Drosophila imaginal disks: negative regulation of decapentaplegic and patched expression by engrailed. 745-56 During development of the Drosophila adult appendage precursors, the larval imaginal disks, the decapentaplegic (dpp) gene is expressed in a stripe just anterior to the anterior/posterior (A/P) compartment boundary. Here, we investigate the genetic controls that lead to production of this stripe. We extend previous observations on leaky engrailed (en) mutations by showing that mutant clones completely lacking both en and invected (inv) activity ectopically express dpp-lacZ reporter genes in the posterior compartment, where dpp activity ordinarily is repressed. Similarly, patched (ptc) is also ectopically expressed in such posterior compartment en-inv- null clones. In contrast, these en-inv- clones exhibit loss of hedgehog (hh) expression. We suggest that the absence of dpp expression in the posterior compartment is due to direct repression by en. Ubiquitious expression of en in imaginal disks, produced by a hs-en construct, eliminates the expression of dpp-lacZ in its normal A/P boundary stripe. We identify three in vitro Engrailed binding sites in one of our dpp-lacZ reporter gene. Mutagenesis of these Engrailed binding sites results in ectopic expression of this reporter gene, but does not alter the normal stripe of expression at the A/P boundary. We propose that the en-hh-ptc regulatory loop that is responsible for segmental expression of wingless in the embryo is reutilized in imaginal disks to create a stripe of dpp expression along the A/P compartment boundary. Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Sanicola M M Sekelsky J J Elson S S Gelbart W M WM eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Hormones 0 Membrane Proteins 0 Proteins 0 Recombinant Fusion Proteins 0 Transcription Factors 0 dpp protein, Drosophila 0 engrail protein, Drosophila 0 invected protein 0 patched protein, Drosophila 149291-21-4 hedgehog protein, Drosophila 9007-49-2 DNA IM Animal Base Sequence Binding Sites DNA metabolism Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Genes, Reporter genetics Insect Hormones biosynthesis genetics metabolism Larva Membrane Proteins biosynthesis genetics Molecular Sequence Data Mutation physiology Proteins biosynthesis genetics Recombinant Fusion Proteins biosynthesis Support, U.S. Gov't, P.H.S. Transcription Factors biosynthesis genetics metabolism Wing growth & development FBrf0049563 90126392 2612381 1990 03 08 1990 03 08 2000 12 18

0950-1991 107 3 1989 Nov Complex spatio-temporal accumulation of alternative transcripts from the neurogenic gene Delta during Drosophila embryogenesis. 623-36 Delta (Dl) function is required for proper specification of epidermal and neural lineages within the neurogenic ectoderm of Drosophila melanogaster. We have determined the spatial accumulation of five Dl transcripts that arise as the result of alternative RNA processing during embryogenesis. We find that these transcripts accumulate in all cells of the neurogenic ectoderm immediately preceding neuroblast segregation, indicating that transcription of Dl does not differ between presumptive neuroblasts and presumptive dermoblasts. Dl transcripts also accumulate transiently in mesodermal and endodermal cells, suggesting that Dl may function in developmental processes in addition to differentiation of the neurogenic ectoderm. We find that three of the Dl transcripts are localized to the base of the nucleus during cellularization. The apparent association of these three transcripts with polysomes suggests that they accumulate within the cytoplasm at the nuclear periphery and is consistent with the hypothesis that Dl encodes multiple translational products. Department of Biology, Indiana University, Bloomington 47405. Kopczynski C C CC Muskavitch M A MA eng Journal Article

ENGLAND Development 8701744 0 RNA, Messenger IM Animal Autoradiography Cell Compartmentation Cell Differentiation genetics Central Nervous System embryology Centrifugation, Zonal Cytoplasm Drosophila embryology genetics Ectoderm physiology Epidermis embryology Genes, Structural genetics Nuclear Envelope Nucleic Acid Hybridization Polyribosomes RNA, Messenger metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic genetics FBrf0052004 91032954 2172079 1990 12 13 1990 12 13 2000 12 18

0016-6758 26 7 1990 Jul [Superunstable systems in Drosophila melanogaster. Analysis of mutations in signed and cut loci] 1133-43 The lines of the M'-cytotype characterized by a long-term instability (which was shown to be conditioned by transpositions of the new mobile element, Stalker) were hybridized with the P-line. This resulted in the appearance of a number of superunstable mutations at the yellow, white, singed, ocelliless and some other loci. The authors analyzed four independently obtained families of superunstable mutations at the singed locus. A wide spectrum of derivatives and high frequency of mutations were demonstrated, as well as the regularities of allelic transitions. Besides this, mutagenesis at the cut locus was observed in the chromosomes carrying sn mutations with frequency of 5.05 x 10(4). By means of the blot analysis it has been shown that most of ct mutations are intragenic deficiencies, ranging from 1.3 to 3 Kb, whose appearance is, conceivably, attributed to the inaccuracy of the insertion excision (the insertion is present but fails to alter the phenotype) at the cut locus of the chromosomes with the superunstable sn-alleles. In the lines with the sn- and ct-mutations the transpositions of the P-element and the Stalker were found, which indicates their involvement in mutagenesis. The authors discuss possible effects of inserting the complicated constructions, based on the combinations of P-element and the Stalker, on the induction of superinstability. Ladvishchenko A B AB Mogila V A VA Georgiev P G PG Simonova O B OB Buff E M EM Gerasimova T I TI rus Journal Article Supernestabil'nye sistemy u Drosophila melanogaster. Analiz mutatsiĭ v lokusakh signed i cut.

USSR Genetika 0047354 0 DNA Transposable Elements IM Alleles Animal DNA Transposable Elements Drosophila melanogaster genetics English Abstract Gene Frequency Mutation Restriction Mapping FBrf0105343 99042011 9822716 1998 12 23 1998 12 23 2002 11 01

0021-9258 273 48 1998 Nov 27 Identification and characterization of a novel line of Drosophila Schneider S2 cells that respond to wingless signaling. 32353-9 Wingless (Wg) treatment of Drosophila wing disc clone 8 cells leads to Armadillo (Arm) protein elevation, and this effect has been used as the basis of in vitro assays for Wg protein. Previously analyzed stocks of Drosophila Schneider S2 cells could not respond to added Wg, because they lack the Wg receptor, Dfrizzled-2. However, we found that a line of S2 cells obtained from another source express Dfrizzled-2 and Dfrizzled-1. Thus, we designated this cell line as S2R+ (S2 receptor plus). S2R+ cells respond to addition of extracellular Wg by elevating Arm and DE-cadherin protein levels and by hyperphosphorylating Dsh, just as clone 8 cells do. Moreover, overexpression of Wg in S2R+, but not in S2 cells, induced the same changes in Dsh, Arm, and DE-cadherin proteins as induced in clone 8 cells, indicating that these events are common effects of Wg signaling, which occurs in cells expressing functional Wg receptors. In addition, unphosphorylated Dsh protein in S2 cells was phosphorylated as a consequence of expression of Dfrizzled-2 or mouse Frizzled-6, suggesting that basal structures common to various frizzled family proteins trigger this phosphorylation of Dsh. S2R+ cells are as sensitive to Wg as are clone 8 cells but can grow in simpler medium. Therefore, the S2R+ cell line is likely to prove highly useful for in vitro analyses of Wg signaling. Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan. syanagaw@virus1.virus.kyoto-u.ac.jp Yanagawa S S Lee J S JS Ishimoto A A eng Journal Article

UNITED STATES J Biol Chem 2985121R 0 Insect Proteins 0 Membrane Glycoproteins 0 Proto-Oncogene Proteins 0 Receptors, Cell Surface 0 Recombinant Proteins 0 armadillo protein, Drosophila 0 frizzled-2 protein, insect 0 frizzled-6 protein 117758-26-6 wingless protein, Drosophila IM Animal Cell Line Clone Cells Drosophila melanogaster Insect Proteins biosynthesis genetics Membrane Glycoproteins physiology Mice Phosphorylation Proto-Oncogene Proteins genetics physiology Receptors, Cell Surface genetics physiology Recombinant Proteins metabolism Signal Transduction physiology Support, Non-U.S. Gov't Transfection FBrf0129944 20469361 11014822 2000 10 25 2000 11 30

0016-6731 156 2 2000 Oct Identification of autosomal regions involved in Drosophila Raf function. 763-74 Raf is an essential downstream effector of activated p21(Ras) (Ras) in transducing proliferation or differentiation signals. Following binding to Ras, Raf is translocated to the plasma membrane, where it is activated by a yet unidentified "Raf activator." In an attempt to identify the Raf activator or additional molecules involved in the Raf signaling pathway, we conducted a genetic screen to identify genomic regions that are required for the biological function of Drosophila Raf (Draf). We tested a collection of chromosomal deficiencies representing approximately 70% of the autosomal euchromatic genomic regions for their abilities to enhance the lethality associated with a hypomorphic viable allele of Draf, Draf(Su2). Of the 148 autosomal deficiencies tested, 23 behaved as dominant enhancers of Draf(Su2), causing lethality in Draf(Su2) hemizygous males. Four of these deficiencies identified genes known to be involved in the Drosophila Ras/Raf (Ras1/Draf) pathway: Ras1, rolled (rl, encoding a MAPK), 14-3-3epsilon, and bowel (bowl). Two additional deficiencies removed the Drosophila Tec and Src homologs, Tec29A and Src64B. We demonstrate that Src64B interacts genetically with Draf and that an activated form of Src64B, when overexpressed in early embryos, causes ectopic expression of the Torso (Tor) receptor tyrosine kinase-target gene tailless. In addition, we show that a mutation in Tec29A partially suppresses a gain-of-function mutation in tor. These results suggest that Tec29A and Src64B are involved in Tor signaling, raising the possibility that they function to activate Draf. Finally, we discovered a genetic interaction between Draf(Su2) and Df(3L)vin5 that revealed a novel role of Draf in limb development. We find that loss of Draf activity causes limb defects, including pattern duplications, consistent with a role for Draf in regulation of engrailed (en) expression in imaginal discs. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. Li W W Noll E E Perrimon N N eng Journal Article

UNITED STATES Genetics 0374636 EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Animal Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics physiology Enhancer Elements (Genetics) Female Gene Deletion Gene Expression Regulation, Developmental Larva Male Mutagenesis Phenotype Proto-Oncogene Proteins c-raf genetics metabolism Signal Transduction Support, Non-U.S. Gov't Transcription, Genetic FBrf0086423 96194053 8631272 1996 07 02 1996 07 02 2002 11 01

0950-1991 122 3 1996 Mar The Drosophila genes crumbs and stardust are involved in the biogenesis of adherens junctions. 951-9 Morphogenetic movements of epithelia during development underlie the normal elaboration of the final body plan. The tissue integrity critical for these movements is conferred by anchorage of the cytoskeleton by adherens junctions, initially spot and later belt-like, zonular structures, which encircle the apical side of the cell. Loss-of-function mutations in the Drosophila genes crumbs and stardust lead to the loss of cell polarity in most ectodermally derived epithelia, followed in some, such as the epidermis, by extensive apoptosis. Here we show that both mutants fail to establish proper zonulae adherentes in the epidermis. Our results suggest that the two genes are involved in different aspects of this process. Further, they are compatible with the hypothesis that crumbs delimits the apical border, where the zonula adherens usually forms and where Crumbs protein is normally most abundant. In contrast, stardust seems to be required at an earlier stage for the assembly of the spot adherence junctions. In both mutants, the defect observed at the ultrastructural level are preceded by a misdistribution of Armadillo and DE-cadherin, the homologues of beta-catenin and E-cadherin, respectively, which are two constituents of the vertebrate adherens junctions. Strikingly, expansion of the apical membrane domain in epidermal cells by overexpression of crumbs also abolishes the formation of adherens junctions and results in the disruption of tissue integrity, but without loss of membrane polarity. This result supports the view that membrane polarity is independent of the formation of adherens junctions in epidermal cells. Institut für Entwicklungsbiologie, Universität zu Köln, Germany. Grawe F F Wodarz A A Lee B B Knust E E Skaer H H eng Journal Article

ENGLAND Development 8701744 0 Cadherins 0 Membrane Proteins 0 Proteins 0 armadillo protein, Drosophila 0 crb protein, Drosophila IM Animal Cadherins metabolism Cell Adhesion Cell Differentiation Cell Polarity Drosophila melanogaster embryology genetics Ectoderm cytology Genes, Structural, Insect Intercellular Junctions ultrastructure Membrane Proteins physiology Microscopy, Electron Proteins metabolism Support, Non-U.S. Gov't FBrf0112095 20032756 10559900 1999 12 16 1999 12 16 2002 11 01

1465-7392 1 3 1999 Jul A new Drosophila APC homologue associated with adhesive zones of epithelial cells. 144-51 Adenomatous polyposis coli protein (APC) is an important tumour suppressor in the human colon epithelium. In a complex with glycogen synthase kinase-3 (GSK-3), APC binds to and destabilizes cytoplasmic ('free') beta-catenin. Here, using a yeast two-hybrid screen for proteins that bind to the Drosophila beta-catenin homologue, Armadillo, we identify a new Drosophila APC homologue, E-APC. E-APC also binds to Shaggy, the Drosophila GSK-3 homologue. Interference with E-APC function produces embryonic phenotypes like those of shaggy mutants. Interestingly, E-APC is concentrated in apicolateral adhesive zones of epithelial cells, along with Armadillo and E-cadherin, which are both integral components of the adherens junctions in these zones. Various mutant conditions that cause dissociation of E-APC from these zones also obliterate the segmental modulation of free Armadillo levels that is normally induced by Wingless signalling. We propose that the Armadillo-destabilizing protein complex, consisting of E-APC, Shaggy, and a third protein, Axin, is anchored in adhesive zones, and that Wingless signalling may inhibit the activity of this complex by causing dissociation of E-APC from these zones. MRC Laboratory of Molecular Biology, Cambridge, UK. Yu X X Waltzer L L Bienz M M eng Journal Article

ENGLAND Nat Cell Biol 100890575 0 Adenomatous Polyposis Coli Protein 0 Cytoskeletal Proteins 0 Insect Proteins 0 RNA, Double-Stranded 0 armadillo protein, Drosophila IM Adenomatous Polyposis Coli Protein Amino Acid Sequence Animal Binding Sites Cell Adhesion Cell Membrane physiology ultrastructure Cytoskeletal Proteins chemistry genetics metabolism Drosophila melanogaster genetics physiology Epithelial Cells cytology physiology Genes, APC Human Insect Proteins metabolism Microscopy, Confocal Molecular Sequence Data Phenotype RNA, Double-Stranded genetics Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0091073 97144426 8990193 1997 02 13 1997 02 13 2002 11 01

0027-8424 94 1 1997 Jan 7 A Drosophila homolog of the tumor suppressor gene adenomatous polyposis coli down-regulates beta-catenin but its zygotic expression is not essential for the regulation of Armadillo. 242-7 Mutations in the adenomatous polyposis coli gene (which encodes a protein called APC) are associated with the formation of intestinal polyps and colon cancers. To facilitate the functional study of APC we have isolated its Drosophila homolog (D-APC) by screening an expression library with an antibody against human APC. The isolated cDNA encodes a predicted 2416-amino acid protein containing significant homology to multiple domains of mammalian APCs. D-APC has seven complete armadillo repeats with 60% identity to its human homolog, one beta-catenin binding site, and up to 7 copies of a 20-amino acid repeat with the average of 50% identity to human APC at amino acid level. D-APC, like its human counterpart, also contains a basic domain. Expression of the domain of D-APC homologous to the region required for beta-catenin down-regulation resulted in down-regulation of intracellular beta-catenin in a mammalian cell line. This same region bound to the Armadillo (Arm) protein, in vitro, the Drosophila homolog of beta-catenin. D-APC RNA and protein expression is very low, if detectable at all, during stages when Arm protein accumulates in a striped pattern in the epidermis of the Drosophila embryos. Removing zygotic D-APC expression did not alter Arm protein distribution, and the final cuticle pattern was not affected significantly. As observed in the rodent, high levels of D-APC expression have been detected in the central nervous system, suggesting a role for D-APC in central nervous system formation. Department of Molecular Biology, Princeton University, NJ 08540, USA. Hayashi S S Rubinfeld B B Souza B B Polakis P P Wieschaus E E Levine A J AJ eng GENBANK U77947 Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Adenomatous Polyposis Coli Protein 0 Cytoskeletal Proteins 0 Insect Proteins 0 armadillo protein, Drosophila 146409-33-8 beta catenin IM Adenomatous Polyposis Coli Protein Amino Acid Sequence Animal Carcinoma genetics Cloning, Molecular Colonic Neoplasms genetics Comparative Study Conserved Sequence Cytoskeletal Proteins genetics immunology metabolism Down-Regulation Drosophila melanogaster embryology genetics Genes, APC Genes, Insect Human In Situ Hybridization Insect Proteins genetics Molecular Sequence Data Nervous System chemistry embryology Protein Binding Sequence Analysis, DNA Sequence Homology, Amino Acid Tumor Cells, Cultured Zygote FBrf0144903 21850437 11861566 2002 02 25 2002 05 24

0016-6731 160 2 2002 Feb Rough eye is a gain-of-function allele of amos that disrupts regulation of the proneural gene atonal during Drosophila retinal differentiation. 623-35 The regular organization of the ommatidial lattice in the Drosophila eye originates in the precise regulation of the proneural gene atonal (ato), which is responsible for the specification of the ommatidial founder cells R8. Here we show that Rough eye (Roi), a dominant mutation manifested by severe roughening of the adult eye surface, causes defects in ommatidial assembly and ommatidial spacing. The ommatidial spacing defect can be ascribed to the irregular distribution of R8 cells caused by a disruption of the patterning of ato expression. Disruptions in the recruitment of other photoreceptors and excess Hedgehog production in differentiating cells may further contribute to the defects in ommatidial assembly. Our molecular characterization of the Roi locus demonstrates that it is a gain-of-function mutation of the bHLH gene amos that results from a chromosomal inversion. We show that Roi can rescue the retinal developmental defect of ato1 mutants and speculate that amos substitutes for some of ato's function in the eye or activates a residual function of the ato1 allele. Department of Anatomy, University of California, San Francisco, California 94143, USA. chanut@itsa.ucsf.edu Chanut Françoise F Woo Katherine K Pereira Shalini S Donohoe Terrence J TJ Chang Shang-Yu SY Laverty Todd R TR Jarman Andrew P AP Heberlein Ulrike U eng EY-11410 EY NEI Journal Article

United States Genetics 0374636 0 Amos protein 0 DNA-Binding Proteins 0 Nerve Growth Factors 0 ato protein IM Alleles Animal DNA-Binding Proteins genetics physiology Drosophila melanogaster embryology genetics physiology Epistasis, Genetic Gene Expression Regulation, Developmental Nerve Growth Factors genetics physiology Retina embryology physiology Signal Transduction genetics physiology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transgenes genetics physiology FBrf0055013 91126085 1899484 1991 03 08 1991 03 08 2000 12 18

0027-8424 88 3 1991 Feb 1 Genetic and molecular characterization of tube, a Drosophila gene maternally required for embryonic dorsoventral polarity. 810-4 Loss of maternal function of the tube gene disrupts a signaling pathway required for pattern formation in Drosophila, causing cells throughout the embryo to adopt the fate normally reserved for those at the dorsal surface. Here we demonstrate that tube mutations also have a zygotic effect on pupal morphology and that this phenotype is shared by mutations in Toll and pelle, two genes with apparent intracellular roles in determining dorsoventral polarity. We then describe the isolation of a functionally full-length tube cDNA identified in a phenotypic rescue assay. The tube mRNA is expressed maximally early in embryogenesis and again late in larval development, corresponding to required periods of tube activity as defined by distinct maternal and zygotic loss-of-function phenotypes in tube mutants. Sequence analysis of the cDNA indicates that the tube protein contains five copies of an eight-residue motif and shares no significant sequence similarity with known proteins. These results suggest that tube represents a class of protein active in signal transduction at two stages of development. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235. Letsou A A Alexander S S Orth K K Wasserman S A SA eng GENBANK M59501 M74563 M94197 M94198 M94199 M94200 S55106 S55153 S55154 X53420 Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 IM tub Amino Acid Sequence Animal Base Sequence Chromosome Walking Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Female Genes Molecular Sequence Data Phenotype Pupa Support, Non-U.S. Gov't Zygote physiology FBrf0109491 99339918 10409506 1999 10 08 1999 10 08 2001 11 02

0950-1991 126 16 1999 Aug Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling. 3607-16 Hedgehog (HH) is an important morphogen involved in pattern formation during Drosophila embryogenesis and disc development. cubitus interruptus (ci) encodes a transcription factor responsible for transducing the hh signal in the nucleus and activating hh target gene expression. Previous studies have shown that CI exists in two forms: a 75 kDa proteolytic repressor form and a 155 kDa activator form. The ratio of these forms, which is regulated positively by hh signaling and negatively by PKA activity, determines the on/off status of hh target gene expression. In this paper, we demonstrate that the exogenous expression of CI that is mutant for four consensus PKA sites [CI(m1-4)], causes ectopic expression of wingless (wg) in vivo and a phenotype consistent with wg overexpression. Expression of CI(m1-4), but not CI(wt), can rescue the hh mutant phenotype and restore wg expression in hh mutant embryos. When PKA activity is suppressed by expressing a dominant negative PKA mutant, the exogenous expression of CI(wt) results in overexpression of wg and lethality in embryogenesis, defects that are similar to those caused by the exogenous expression of CI(m1-4). In addition, we demonstrate that, in cell culture, the mutation of any one of the three serine-containing PKA sites abolishes the proteolytic processing of CI. We also show that PKA directly phosphorylates the four consensus phosphorylation sites in vitro. Taken together, our results suggest that positive hh and negative PKA regulation of wg gene expression converge on the regulation of CI phosphorylation. Vollum Institute and Department of Cell and Developmental Biology L-215, Oregon Health Sciences University, Portland, OR 97201, USA. Chen Y Y Cardinaux J R JR Goodman R H RH Smolik S M SM eng DK44239 DK NIDDK Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 cubitus interruptus protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Animals, Genetically Modified Binding Sites Body Patterning Consensus Sequence Cyclic AMP-Dependent Protein Kinases metabolism DNA-Binding Proteins chemistry genetics metabolism Drosophila melanogaster embryology genetics Insect Proteins genetics physiology Morphogenesis Peptide Mapping Phosphorylation Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection Zinc Fingers FBrf0145168 21864574 11875444 2002 03 04 2002 10 11

1465-7392 4 3 2002 Mar Selector and signalling molecules cooperate in organ patterning. E48-51 Cell signalling is essential for a plethora of inductive interactions during organogenesis. Surprisingly, only a few different classes of signalling molecules mediate many inductive interactions, and these molecules are used reiteratively during development. This raises the question of how generic signals can trigger tissue-specific responses. Recent studies in Drosophila melanogaster indicate that signalling molecules cooperate with selector genes to specify particular body parts and organ types. Selector and signalling inputs are integrated at the level of cis-regulatory elements, where direct binding of both selector proteins and signal transducers is required to activate tissue-specific enhancer elements of target genes. Such enhancers include autoregulatory enhancers of the selector genes themselves, which drive the refinement of expression patterns of selector genes. Department of Molecular, Cell and Developmental Biology, Mt. Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029, USA. Curtiss Jennifer J Halder Georg G Mlodzik Marek M eng Journal Article Review Review, Tutorial

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 Receptors, Invertebrate Peptide 0 epidermal growth factor receptor homolog, Drosophila 0 notch protein 117758-26-6 wingless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Body Patterning genetics physiology Drosophila Proteins genetics metabolism Drosophila melanogaster genetics growth & development metabolism Enhancer Elements (Genetics) Eye growth & development Gene Expression Regulation, Developmental Genes, Insect Membrane Proteins genetics Models, Biological Proto-Oncogene Proteins genetics Receptor, Epidermal Growth Factor genetics Receptors, Invertebrate Peptide genetics Signal Transduction Wing growth & development 47 FBrf0079386 95203683 7896096 1995 04 26 1995 04 26 2002 10 21

0016-6731 138 4 1994 Dec sine oculis is a homeobox gene required for Drosophila visual system development. 1137-50 The somda (sine oculis-medusa) mutant is the result of a P element insertion at position 43C on the second chromosome. somda causes aberrant development of the larval photoreceptor (Bolwig's) organ and the optic lobe primordium in the embryo. Later in development, adult photoreceptors fail to project axons into the optic ganglion. Consequently optic lobe development is aborted and photoreceptor cells show age-dependent retinal degeneration. The so gene was isolated and characterized. The gene encodes a homeodomain protein expressed in the optic lobe primordium and Bolwig's organ of embryos, in the developing adult visual system of larvae, and in photoreceptor cells and optic lobes of adults. In addition, the SO product is found at invagination sites during embryonic development: at the stomadeal invagination, the cephalic furrow, and at segmental boundaries. The mutant somda allele causes severe reduction of SO embryonic expression but maintains adult visual system expression. Ubiquitous expression of the SO gene product in 4-8-hr embryos rescues all somda mutant abnormalities, including the adult phenotypes. Thus, all deficits in adult visual system development and function results from failure to properly express the so gene during embryonic development. This analysis shows that the homeodomain containing SO gene product is involved in the specification of the larval and adult visual system development during embryogenesis. Department of Biological Sciences, University of Notre Dame, Indiana 46556. Serikaku M A MA O'Tousa J E JE eng GENBANK S77459 NEIEY06808 EY NEI Journal Article

UNITED STATES Genetics 0374636 0 Eye Proteins 0 Recombinant Fusion Proteins 0 sine oculis protein, Drosophila IM so so<up>mda</up> Amino Acid Sequence Animal Axons ultrastructure Base Sequence Comparative Study Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian growth & development Eye embryology growth & development Eye Proteins genetics physiology Gene Expression Regulation, Developmental Genes, Homeobox Genes, Structural, Insect Larva growth & development Molecular Sequence Data Mutagenesis, Insertional Optic Lobe embryology growth & development Phenotype Photoreceptors, Invertebrate embryology growth & development Recombinant Fusion Proteins biosynthesis Retinal Degeneration embryology genetics Sequence Alignment Sequence Homology Support, U.S. Gov't, P.H.S. Visual Pathways embryology growth & development FBrf0155786 22390911 12502740 2002 12 27 2003 01 23 2003 06 16

0890-9369 16 24 2002 Dec 15 Biological functions of the ISWI chromatin remodeling complex NURF. 3186-98 The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form. Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892-4255, USA. Badenhorst Paul P Voas Matthew M Rebay Ilaria I Wu Carl C eng Journal Article

United States Genes Dev 8711660 0 Chromatin 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Heat-Shock Proteins 70 0 ISWI protein 0 Insect Proteins 0 Nucleosomes 0 Transcription Factors 0 enhancer of bithorax protein, Drosophila 0 heat shock activator protein, Drosophila EC 3.6.1.3 Adenosinetriphosphatase IM Adenosinetriphosphatase physiology Animal Animals, Genetically Modified Chromatin metabolism DNA-Binding Proteins metabolism Drosophila Proteins metabolism Drosophila melanogaster embryology genetics metabolism Gene Expression Regulation drug effects physiology Genes, Homeobox genetics Heat-Shock Proteins 70 metabolism Hematopoiesis physiology Insect Proteins genetics metabolism physiology Larva growth & development metabolism Mutagenesis, Site-Directed Neuroectodermal Tumor, Melanotic genetics metabolism Nucleosomes physiology Sex Chromosome Aberrations Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics) drug effects physiology Transcription Factors physiology X Chromosome genetics FBrf0158873 22507947 12620977 2003 03 06 2003 06 16 2003 09 08

0950-1991 130 8 2003 Apr The dead ringer/retained transcriptional regulatory gene is required for positioning of the longitudinal glia in the Drosophila embryonic CNS. 1505-13 The Drosophila dead ringer (dri, also known as retained, retn) gene encodes a nuclear protein with a conserved DNA-binding domain termed the ARID (AT-rich interaction domain). We show here that dri is expressed in a subset of longitudinal glia in the Drosophila embryonic central nervous system and that dri forms part of the transcriptional regulatory cascade required for normal development of these cells. Analysis of mutant embryos revealed a role for dri in formation of the normal embryonic CNS. Longitudinal glia arise normally in dri mutant embryos, but they fail to migrate to their final destinations. Disruption of the spatial organization of the dri-expressing longitudinal glia accounts for the mild defects in axon fasciculation observed in the mutant embryos. Consistent with the late phenotypes observed, expression of the glial cells missing (gcm) and reversed polarity (repo) genes was found to be normal in dri mutant embryos. However, from stage 15 of embryogenesis, expression of locomotion defects (loco) and prospero (pros) was found to be missing in a subset of LG. This suggests that loco and pros are targets of DRI transcriptional activation in some LG. We conclude that dri is an important regulator of the late development of longitudinal glia. Centre for the Molecular Genetics of Development, Adelaide University, Adelaide SA 5005, Australia. Shandala Tetyana T Takizawa Kazunaga K Saint Robert R eng Journal Article

England Development 8701744 0 Cut protein 0 Homeodomain Proteins 0 LOCO protein 0 Nerve Tissue Proteins 0 Nuclear Proteins 0 dead ringer protein 0 repo protein, Drosophila 142540-63-4 prospero protein IM Animal Cell Size Central Nervous System cytology embryology Drosophila melanogaster anatomy & histology embryology physiology Homeodomain Proteins genetics metabolism Immunohistochemistry Nerve Tissue Proteins metabolism Neuroglia cytology physiology Neurons cytology physiology Nuclear Proteins genetics metabolism Phenotype Signal Transduction physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0080317 95229056 7713427 1995 05 18 1995 05 18 2002 11 01

0016-6731 139 2 1995 Feb Identification of regions interacting with ovoD mutations: potential new genes involved in germline sex determination or differentiation in Drosophila melanogaster. 713-32 Only a few Drosophila melanogaster germline sex determination genes are known, and there have been no systematic screens to identify new genes involved in this important biological process. The ovarian phenotypes produced by females mutant for dominant alleles of the ovo gene are modified in flies with altered doses of other loci involved in germline sex determination in Drosophila (Sex-lethal+, sans fille+ and ovarian tumor+). This observation constitutes the basis for a screen to identify additional genes required for proper establishment of germline sexual identity. We tested 300 deletions, which together cover approximately 58% of the euchromatic portion of the genome, for genetic interactions with ovoD. Hemizygosity for more than a dozen small regions show interactions that either partially suppress or enhance the ovarian phenotypes of females mutant for one or more of the three dominant ovo mutations. These regions probably contain genes whose products act in developmental hierarchies that include ovo+ protein. Department of Genetics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA. Pauli D D Oliver B B Mahowald A P AP eng HD-17608 HD NICHD T32-HD07104 HD NICHD Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Insect Hormones 0 Sxl protein, Drosophila 0 Transcription Factors 0 ovo protein IM ovo Alleles Animal Crosses, Genetic DNA-Binding Proteins genetics Drosophila melanogaster genetics Female Genes, Insect physiology Insect Hormones genetics Male Oogenesis genetics Phenotype Sequence Deletion physiology Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Transcription Factors genetics X Chromosome FBrf0111888 20042299 10572054 2000 01 21 2000 01 21 2003 08 29

0950-1991 126 24 1999 Dec Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway. 5795-808 During Drosophila eye development, Hedgehog (Hh) protein secreted by maturing photoreceptors directs a wave of differentiation that sweeps anteriorly across the retinal primordium. The crest of this wave is marked by the morphogenetic furrow, a visible indentation that demarcates the boundary between developing photoreceptors located posteriorly and undifferentiated cells located anteriorly. Here, we present evidence that Hh controls progression of the furrow by inducing the expression of two downstream signals. The first signal, Decapentaplegic (Dpp), acts at long range on undifferentiated cells anterior to the furrow, causing them to enter a 'pre-proneural' state marked by upregulated expression of the transcription factor Hairy. Acquisition of the pre-proneural state appears essential for all prospective retinal cells to enter the proneural pathway and differentiate as photoreceptors. The second signal, presently unknown, acts at short range and is transduced via activation of the Serine-Threonine kinase Raf. Activation of Raf is both necessary and sufficient to cause pre-proneural cells to become proneural, a transition marked by downregulation of Hairy and upregulation of the proneural activator, Atonal (Ato), which initiates differentiation of the R8 photoreceptor. The R8 photoreceptor then organizes the recruitment of the remaining photoreceptors (R1-R7) through additional rounds of Raf activation in neighboring pre-proneural cells. Finally, we show that Dpp signaling is not essential for establishing either the pre-proneural or proneural states, or for progression of the furrow. Instead, Dpp signaling appears to increase the rate of furrow progression by accelerating the transition to the pre-proneural state. In the abnormal situation in which Dpp signaling is blocked, Hh signaling can induce undifferentiated cells to become pre-proneural but does so less efficiently than Dpp, resulting in a retarded rate of furrow progression and the formation of a rudimentary eye. Howard Hughes Medical Institute, Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. simong@itsa.ucsf.edu Greenwood S S Struhl G G eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Receptors, Cell Surface 0 Receptors, Fibroblast Growth Factor 0 Receptors, Invertebrate Peptide 0 Repressor Proteins 0 ato protein 0 dpp protein, Drosophila 0 epidermal growth factor receptor homolog, Drosophila 127385-83-5 hairy protein, insect 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- DTFR protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.112 heartless protein, Drosophila EC 2.7.1.112 htl protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Animal Animals, Genetically Modified Cell Differentiation DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Insect Proteins genetics metabolism physiology Photoreceptors, Invertebrate embryology Protein-Serine-Threonine Kinases genetics metabolism Proto-Oncogene Proteins c-raf genetics metabolism physiology Receptor, Epidermal Growth Factor genetics metabolism Receptors, Cell Surface genetics metabolism Receptors, Fibroblast Growth Factor genetics metabolism Receptors, Invertebrate Peptide genetics metabolism Repressor Proteins genetics metabolism Signal Transduction Support, Non-U.S. Gov't FBrf0147170 21973244 11976688 2002 04 26 2002 05 07

0028-0836 416 6883 2002 Apr 25 AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila. 870-4 Activity-regulated gene expression mediates many aspects of neural plasticity, including long-term memory. In the prevailing view, patterned synaptic activity causes kinase-mediated activation of the transcription factor cyclic AMP response-element-binding protein, CREB. Together with appropriate cofactors, CREB then transcriptionally induces a group of 'immediate early' transcription factors and, eventually, effector proteins that establish or consolidate synaptic change. Here, using a Drosophila model synapse, we analyse cellular functions and regulation of the best known immediate early transcription factor, AP-1; a heterodimer of the basic leucine zipper proteins Fos and Jun. We observe that AP-1 positively regulates both synaptic strength and synapse number, thus showing a greater range of influence than CREB. Observations from genetic epistasis and RNA quantification experiments indicate that AP-1 acts upstream of CREB, regulates levels of CREB messenger RNA, and functions at the top of the hierarchy of transcription factors known to regulate long-term plasticity. A Jun-kinase signalling module provides a CREB-independent route for neuronal AP-1 activation; thus, CREB regulation of AP-1 expression may, in some neurons, constitute a positive feedback loop rather than the primary step in AP-1 activation. Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721, USA. Sanyal Subhabrata S Sandstrom David J DJ Hoeffer Charles A CA Ramaswami Mani M eng Journal Article

England Nature 0410462 0 DNA-Binding Protein, Cyclic AMP-Responsive 0 Proto-Oncogene Proteins c-fos 0 Proto-Oncogene Proteins c-jun 0 RNA, Messenger 0 Transcription Factor AP-1 60-92-4 Cyclic AMP EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Animal Cell Count Cyclic AMP metabolism DNA-Binding Protein, Cyclic AMP-Responsive metabolism Dimerization Drosophila melanogaster genetics growth & development metabolism Electrophysiology Epistasis, Genetic Gene Expression Regulation, Developmental Larva genetics growth & development metabolism Mitogen-Activated Protein Kinases metabolism Neuromuscular Junction cytology enzymology growth & development metabolism Neuronal Plasticity Promoter Regions (Genetics) genetics Proto-Oncogene Proteins c-fos metabolism Proto-Oncogene Proteins c-jun metabolism RNA, Messenger genetics metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Synapses enzymology metabolism Transcription Factor AP-1 metabolism FBrf0155933 22447742 12559488 2003 01 31

0925-4773 120 2 2003 Feb Armadillo levels are reduced during mitosis in Drosophila. 157-65 The Armadillo protein of Drosophila melanogaster is both a structural component of adherens junctions at apical cell membranes and also a key cytoplasmic transducer of the Wingless signalling pathway. We have used the Gal4-UAS system to over-express Armadillo in the Drosophila wing: this hyperactivates the Wingless pathway and leads to the formation of ectopic, supernumerary wing bristles. Here, we report that this adult phenotype is dominantly enhanced by mutations in cdc25(string) and, conversely, is suppressed by co-expression of Cdc25(String). Furthermore, we show that the steady state levels of Armadillo protein produced from the UAS transgene are also sensitive to cdc25(string) dosage in the cells of the larval imaginal wing disc. Consistent with the role of Cdc25(String) in promoting mitosis and with our genetic interaction data, we find a strong correlation between progression through mitosis and a reduction in Armadillo levels. Significantly, this is true whether Armadillo is over-expressed or not, and both cytoplasmic (signalling) and membrane-associated (junctional) Armadillo appears to be affected. We conclude that this phenomenon may reduce the efficacy of Wingless signalling and/or intercellular adhesion during cell division. MRC National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, London, UK Marygold Steven J SJ Vincent Jean Paul JP eng Journal Article

Ireland Mech Dev 9101218 IM FBrf0049325 89168430 2493992 1989 05 09 1989 05 09 2000 12 18

0092-8674 56 6 1989 Mar 24 The sex determination locus transformer-2 of Drosophila encodes a polypeptide with similarity to RNA binding proteins. 1011-8 The D. melanogaster transformer-2 (tra-2) gene regulates somatic sexual differentiation in females and is necessary for spermatogenesis in males. Wild-type tra-2 function is required for the female-specific splicing of the pre-mRNA of the next known gene (doublesex) downstream of tra-2 in the sex determination regulatory hierarchy. The tra-2 gene was cloned, and P element-mediated transformation was used to demonstrate that a 3.9 kb genomic fragment contains all sequences necessary for tra-2 function. A 1.7 kb transcript was shown to be the product of the tra-2 locus based on its reduced level in flies containing a tra-2 mutant allele. The sequence of a cDNA corresponding to this transcript indicates that it encodes a polypeptide with strong similarity to a family of RNA binding proteins that includes proteins found associated with hnRNPs and snRNPs, suggesting that the tra-2 product may directly regulate the processing of the double-sex pre-mRNA in females. Department of Biological Sciences, Stanford University, California 94305. Goralski T J TJ Edström J E JE Baker B S BS eng GENBANK J03155 Journal Article

UNITED STATES Cell 0413066 0 Carrier Proteins 0 Peptides 0 RNA, Messenger 0 RNA-Binding Proteins IM Amino Acid Sequence Animal Base Sequence Carrier Proteins genetics Drosophila melanogaster genetics Female Gene Expression Regulation Genes, Regulator Genes, Structural Male Molecular Sequence Data Mutation Peptides analysis genetics pharmacology RNA, Messenger genetics metabolism RNA-Binding Proteins Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Transformation, Genetic FBrf0144831 21870014 11880359 2002 03 06 2002 04 19

0950-1991 129 6 2002 Mar The plakin Short Stop and the RhoA GTPase are required for E-cadherin-dependent apical surface remodeling during tracheal tube fusion. 1509-20 Cells in vascular and other tubular networks require apical polarity in order to contact each other properly and to form lumen. As tracheal branches join together in Drosophila melanogaster embryos, specialized cells at the junction form a new E-cadherin-based contact and assemble an associated track of F-actin and the plakin Short Stop (shot). In these fusion cells, the apical surface determinant Discs Lost (Dlt) is subsequently deposited and new lumen forms along the track. In shot mutant embryos, the fusion cells fail to remodel the initial E-cadherin contact, to make an associated F-actin structure and to form lumenal connections between tracheal branches. Shot binding to F-actin and microtubules is required to rescue these defects. This finding has led us to investigate whether other regulators of the F-actin cytoskeleton similarly affect apical cell surface remodeling and lumen formation. Expression of constitutively active RhoA in all tracheal cells mimics the shot phenotype and affects Shot localization in fusion cells. The dominant negative RhoA phenotype suggests that RhoA controls apical surface formation throughout the trachea. We therefore propose that in fusion cells, Shot may function downstream of RhoA to form E-cadherin-associated cytoskeletal structures that are necessary for apical determinant localization. Department of Cell Biology and Center for Molecular Neuroscience, C-2210 Medical Center North,Vanderbilt University Medical Center, Nashville, TN 37232-0295, USA. Lee Seungbok S Kolodziej Peter A PA eng 1R01 GM/HL61202-01A1 GM NIGMS Journal Article

England Development 8701744 0 Cadherins 0 Drosophila Proteins 0 Microfilament Proteins 0 short stop protein, Drosophila EC 3.6.1.- rhoA GTP-Binding Protein IM Animal Cadherins physiology Cell Differentiation Cell Polarity physiology Cytoskeleton physiology Drosophila Proteins physiology Drosophila melanogaster embryology physiology Microfilament Proteins physiology Morphogenesis Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trachea embryology physiology rhoA GTP-Binding Protein physiology FBrf0073309 95051114 7962198 1994 11 29 1994 11 29 2000 12 18

0021-9533 107 ( Pt 6) 1994 Jun A cytoplasmic dynein motor in Drosophila: identification and localization during embryogenesis. 1557-69 We have characterized a cytoplasmic dynein motor isoform that is present in extracts of Drosophila embryos. A prominent high molecular weight (HMW) polypeptide (> 400 kDa) is enriched in microtubules prepared from nucleotide-depleted embryonic extracts. Based on its ATP-sensitive microtubule binding activity, 20 S sedimentation coefficient, sensitivity to UV-vanadate and nucleotide specificity, the HMW polypeptide resembles cytoplasmic dyneins prepared from other organisms. The Drosophila cytoplasmic dynein acts as a minus-end motor that promotes microtubule translocation in vitro. A polyclonal antibody raised against the dynein heavy chain polypeptide was used to localize the dynein antigen in whole-mount preparations of embryos by immunofluorescence microscopy. These studies show that the dynein motor is associated with microtubules throughout embryogenesis, including mitotic spindle microtubules and microtubules of the embryonic nervous system. Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108-1020. Hays T S TS Porter M E ME McGrail M M Grissom P P Gosch P P Fuller M T MT McIntosh J R JR eng GM-36663 GM NIGMS GM-44757 GM NIGMS HD-18127 HD NICHD Journal Article

ENGLAND J Cell Sci 0052457 56-65-5 Adenosine Triphosphate EC 3.6.1.33 Dynein ATPase IM Adenosine Triphosphate metabolism Animal Cytoplasm chemistry Drosophila melanogaster chemistry embryology physiology ultrastructure Dynein ATPase analysis physiology Embryo, Nonmammalian chemistry ultrastructure Microscopy, Fluorescence Microtubules chemistry physiology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0086331 96194055 8631274 1996 07 02 1996 07 02 2002 11 01

0950-1991 122 3 1996 Mar Sex-specific control of Sex-lethal is a conserved mechanism for sex determination in the genus Drosophila. 971-82 In D. melanogaster the binary switch gene Sex-lethal (Sxl) plays a pivotal role in somatic sex determination -- when the Sxl gene is on the female pathway is followed, while the male pathway is followed when the gene is off. In the present study we have asked whether the Sxl gene is present in other species of the genus Drosophila and whether it is subject to a similar sex-specific on-off regulation. Sxl proteins were found in all of the drosophilids examined, and they display a sex-specific pattern of expression. Furthermore, characterization of the Sxl gene in the distant drosophilan relative, D. virilis, reveals that the structure and sequence organization of the gene has been well conserved and that, like melanogaster, alternative RNA processing is responsible for its sex-specific expression. Hence, this posttranscriptional on-off regulatory mechanism probably existed before the separation of the drosophilan and sophophoran subgenera and it seems likely that Sxl functions as a sex determination switch gene in most species in the Drosophila genus. Although alternative splicing appears to be responsible for the on-off regulation of the Sxl gene in D. virilis, this species is unusual in that Sxl proteins are present not only in females but also in males. The D. virilis female and male proteins appear to be identical over most of the length except for the amino-terminal approx. 25 aa which are encoded by the differentially spliced exons. In transcriptionally active polytene chromosomes, the male and female proteins bind to the same cytogenetic loci, including the sites corresponding to the D. virilis Sxl and tra genes. Hence, though the male proteins are able to interact with appropriate target pre-mRNAs, they are apparently incapable of altering the splicing pattern of these pre-mRNAs. Department of Molecular Biology, Princeton University, NJ 08544, USA. Bopp D D Calhoun G G Horabin J I JI Samuels M M Schedl P P eng Journal Article

ENGLAND Development 8701744 0 DNA Primers 0 RNA, Messenger 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Alternative Splicing Amino Acid Sequence Animal Base Sequence Chromosome Mapping Consensus Sequence DNA Primers chemistry Drosophila embryology genetics Exons Female Gene Expression Regulation, Developmental Genes, Structural, Insect Male Molecular Sequence Data Protein Binding RNA Splicing RNA, Messenger genetics RNA-Binding Proteins physiology Sex Determination (Analysis) Support, U.S. Gov't, P.H.S. FBrf0102422 98221109 9553046 1998 05 28 1998 05 28 2001 11 02

0890-9369 12 8 1998 Apr 15 Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation. 1166-75 Dorsoventral (D/V) patterning in Drosophila oogenesis is initiated by the transmission of a TGF-alpha-like ligand, Gurken (Grk), from the oocyte to the anterodorsal follicle cells, activating the EGF receptor (Egfr) signaling pathway. The zinc-finger transcription factor CF2 is a negative regulator of the rhomboid (rho) gene that encodes an essential membrane-bound component of the dorsalizing pathway. Expression of CF2 itself is negatively regulated by the activated Egfr. In this report, we demonstrate that CF2 is the target of down-regulation by the MAPK kinase cascade, and that this down-regulation is independent of the Rho function. These results suggest that D/V patterning involves a two-step signaling process: the initial Egfr signal, which represses CF2 and induces rho expression; and the subsequent Egfr + Rho signal, which determines the dorsal cell fates. Furthermore, we show that CF2 down-regulation occurs at the post-translational level through a mechanism involving coupled cytoplasmic retention and degradation. Center for Molecular and Structural Biology and Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA. Mantrova E Y EY Hsu T T eng Journal Article

UNITED STATES Genes Dev 8711660 0 DNA-Binding Proteins 0 Transcription Factors 148813-47-2 transcription factor CF2 EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Mitogen-Activated Protein Kinase Kinases EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 3.6.1.- ras Proteins IM Animal Binding Sites Ca(2+)-Calmodulin Dependent Protein Kinase genetics Cytoplasm metabolism DNA-Binding Proteins genetics Down-Regulation Drosophila melanogaster embryology genetics Mitogen-Activated Protein Kinase Kinases Oogenesis Phosphorylation Protein Kinases genetics Proto-Oncogene Proteins c-raf genetics RNA Processing, Post-Transcriptional Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription Factors genetics Zinc Fingers ras Proteins genetics FBrf0056030 93011672 1397078 1992 10 30 1992 10 30 2000 12 18

0014-4827 202 2 1992 Oct Splicing thermotolerance maintains Pre-mRNA transcripts in the splicing pathway during severe heat shock. 233-42 Thermotolerance, the ability of cells and organisms to withstand severe elevated temperatures after brief exposure to mild elevated temperatures, has been studied in numerous laboratories. Survival thermotolerance is defined as the increase in cell or organism survival at severe elevated temperatures after a pretreatment at mild elevated temperatures. This study examines splicing thermotolerance in Drosophila melanogaster, the ability to splice pre-mRNAs made at the severe temperature (38 degrees C) after a brief pretreatment at a milder temperature (35 degrees C). It is probably one of a number of mechanisms by which cells adapt to heat shock. These experiments demonstrate that pre-mRNAs synthesized at the severe temperatures in splicing thermotolerant cells, although protected in splicing-competent complexes, are not actually processed to mature mRNAs until the cells are returned to their normal temperature. We have also studied the kinetics of acquisition and loss of splicing thermotolerance. As little as 10 min of pretreatment at 35 degrees C was sufficient to provide full splicing thermotolerance to a 30-min severe heat shock of 38 degrees C. Pretreatments of less than 10 min provide partial splicing thermotolerance for a 30-min severe heat shock. Full splicing thermotolerance activity begins to decay about 4 h after the cessation of the 35 degrees C incubation and is completely lost by 8 h after the pretreatment. The kinetics experiments of pre-mRNAs synthesized during the 38 degrees C treatment in splicing thermotolerant cells indicate that one or more splicing thermotolerance factors are synthesized during the 35 degrees C pretreatment which interact with pre-mRNA-containing complexes to keep them in a splicing-competent state. These kinetic experiments also indicate that in cells which are partially splicing thermotolerant, the pre-mRNAs synthesized early during the 38 degrees C incubation are protected, whereas those synthesized late are not. In the absence of splicing thermotolerant factors, the pre-mRNA-containing complexes leave the normal splicing pathway and are allowed to exit to the cytoplasm. Department of Biology and Molecular Genetics Center, Dartmouth College, Hanover, New Hampshire 03755. Corell R A RA Gross R H RH eng GM36057 GM NIGMS Journal Article

UNITED STATES Exp Cell Res 0373226 0 RNA Precursors IM Animal Cells, Cultured Drosophila melanogaster Heat Kinetics Models, Genetic RNA Precursors metabolism RNA Splicing Support, U.S. Gov't, P.H.S. Thermodynamics Transcription, Genetic FBrf0055483 92281548 1596274 1992 06 30 1992 06 30 2000 12 18

0265-9247 14 4 1992 Apr Genetic sex determination mechanisms and evolution. 253-61 Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well-studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development. MRC Laboratory of Molecular Biology, Cambridge, UK. Hodgkin J J eng Journal Article

ENGLAND Bioessays 8510851 IM Animal Caenorhabditis genetics Comparative Study Drosophila genetics Evolution Mice Models, Genetic Phenotype Sex Determination (Analysis) FBrf0076961 94359474 8078475 1994 10 06 1994 10 06 2000 12 18

0026-8925 244 5 1994 Sep 1 Preferential transposition of a Drosophila P element to the corresponding region of the homologous chromosome. 484-90 Genetic and physical analyses have demonstrated an intimate interaction or pairing of homologous chromosomes in the nuclei of many Drosophila cell types. Experiments were performed to determine whether P elements transposing from a given chromosome to its homolog would preferentially insert in the region corresponding to the donor site, perhaps due to such a proximity. A P [lacZ;ry+] element at the cactus locus (35F) on the second chromosome was mobilized and 96 insertions on the homolog were recovered. The distribution of these new insertions was determined by recombination mapping and molecular analysis, and compared with a control set of 93 second-chromosome insertions originating from the X chromosome. A nearly threefold preference was observed for re-insertion in a region of two to three number divisions around cactus on the homolog. However, none of these "local" insertions was actually within approximately 50 kb of the site at cactus corresponding to the starting site. This is in marked contrast to the previously described phenomenon of intrachromosomal local transposition, where the majority of local transpositions are within 10 kb. The data suggest that the mechanisms for intrachromosomal and interchromosomal local transposition are distinct, and are consistent with a model for interchromosomal local transposition involving proximity of homologous chromosomal regions in the nuclei of the germline cells. Department of Biological Sciences, School of Gerontology, University of Southern California, Los Angeles 90089-1340. Tower J J Kurapati R R eng AG00093 AG NIA Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA Transposable Elements IM Animal Chromosomes DNA Transposable Elements Drosophila melanogaster genetics Female Male Mutagenesis, Insertional Recombination, Genetic Support, U.S. Gov't, P.H.S. FBrf0057829 93250035 8485145 1993 06 04 1993 06 04 2000 12 18

0006-2960 32 17 1993 May 4 Expression, purification, and characterization of the Drosophila kinesin motor domain produced in Escherichia coli. 4677-84 The Drosophila kinesin heavy-chain gene was truncated to obtain the N-terminal 401 amino acid motor domain (designated K401) containing both the microtubule and ATP binding sites. The plasmid construct with the truncated kinesin gene was used to transform Escherichia coli. After induction, K401 was expressed as soluble kinesin protein at high levels and purified to homogeneity in milligram quantities. The purified protein was active and behaved as native kinesin with respect to its steady-state kinetic properties: K401 demonstrated a very low ATPase activity (kcat = 0.01 s-1) which was stimulated approximately 1000-fold by the addition of microtubules (kcat = 10 s-1; K0.5,MT = 0.9 microM tubulin; Km,ATP = 31 microM). Like native kinesin, K401 when purified contained ADP tightly bound at its active site, and the release of ADP from the active site occurred at a rate equal to the steady-state ATPase kcat. Active-site measurements using [alpha-32P]ATP demonstrated a stoichiometry of one ATPase site per K401 molecule. Like native kinesin, K401 can also hydrolyze MgGTP, and in the presence of microtubules, the rate of hydrolysis was increased dramatically from 0.03 to 16 s-1 (K0.5,MT = 2 microM tubulin; Km,GTP = 3.5 mM). These results establish that an active kinesin motor domain can be bacterially expressed and that this domain, the N-terminal 401 amino acids of the Drosophila kinesin heavy chain without light chains or additional eukaryotic factors, has full catalytic activity with microtubules.(ABSTRACT TRUNCATED AT 250 WORDS) Department of Molecular and Cell Biology, Pennsylvania State University, University Park 16802. Gilbert S P SP Johnson K A KA eng GM26726 GM NIGMS Journal Article

UNITED STATES Biochemistry 0370623 0 Plasmids 0 Recombinant Proteins 28141-84-6 magnesium GTP 56-65-5 Adenosine Triphosphate 58-64-0 Adenosine Diphosphate 86-01-1 Guanosine Triphosphate EC 3.6.1.- GTP Phosphohydrolases EC 3.6.1.- Kinesin EC 3.6.1.3 Adenosinetriphosphatase IM Adenosine Diphosphate metabolism Adenosine Triphosphate metabolism Adenosinetriphosphatase metabolism Animal Binding Sites Catalysis Drosophila melanogaster chemistry genetics Enzyme Activation Escherichia coli genetics metabolism GTP Phosphohydrolases metabolism Gene Expression Guanosine Triphosphate metabolism Kinesin genetics metabolism Kinetics Microtubules metabolism Plasmids Recombinant Proteins isolation & purification metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transformation, Bacterial FBrf0084726 96170782 8601486 1996 05 06 1996 05 06 2002 11 01

0016-6731 141 4 1995 Dec Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster. 1451-71 Drosophila sex is determined by the action of the X:A chromosome balance on transcription of Sex-lethal (Sxl), a feminizing switch gene. We obtained loss-of-function mutations in denominator elements of the X:A signal by selecting for dominant suppressors of a female-specific lethal mutation in the numerator element, sisterlessA (sisA). Ten suppressors were recovered in this extensive genome-wide selection. All were mutations in deadpan (dpn), a pleiotropic locus previously discovered to be a denominator element. Detailed genetic and molecular characterization is presented of this diverse set of new dpn alleles including their effects on Sxl. Although selected only for impairment of sex-specific functions, all were also impaired in nonsex-specific functions. Male-lethal effects were anticipated for mutations in a major denominator element, but we found that viability of males lacking dpn function was reduced no more than 50% relative to their dpn- sisters. Moreover, loss of dpn activity in males caused only a modest derepression of the Sxl "establishment" promoter (Sxlpe), the X:A target. By itself, dpn cannot account for the masculinizing effect of increased autosomal ploidy, the effect that gave rise to the concept of the X:A ratio; nevertheless, if there are other denominator elements, our results suggest that their individual contributions to the sex-determination signal are even less than that of dpn. The time course of expression of dpn and of Sxl in dpn mutant backgrounds suggests that dpn is required for sex determination only during the later stages of X:A signaling in males to prevent inappropriate expression of Sxlpe in the face of increasing sis gene product levels. Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA. Barbash D A DA Cline T W TW eng GM-23468 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Primers 0 DNA-Binding Proteins 0 Nuclear Proteins 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 149347-68-2 Dpn protein IM Amino Acid Sequence Animal Base Sequence DNA Primers DNA-Binding Proteins genetics Drosophila melanogaster genetics Female Gene Expression Regulation, Developmental Genes, Lethal Genes, Suppressor Genetic Complementation Test Male Molecular Sequence Data Mutation Nuclear Proteins genetics Ploidies RNA-Binding Proteins genetics Sex Determination (Analysis) Support, U.S. Gov't, P.H.S. FBrf0055887 93170175 1289061 1993 03 25 1993 03 25 2000 12 18

0950-1991 116 3 1992 Nov The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. 711-9 The segment polarity gene wingless has an essential function in cell-to-cell communication during various stages of Drosophila development. The wingless gene encodes a secreted protein that affects gene expression in surrounding cells but does not spread far from the cells where it is made. In larvae, wingless is necessary to generate naked cuticle in a restricted part of each segment. To test whether the local accumulation of wingless is essential for its function, we made transgenic flies that express wingless under the control of a hsp70 promoter (HS-wg flies). Uniform wingless expression results in a complete naked cuticle, uniform armadillo accumulation and broadening of the engrailed domain. The expression patterns of patched, cubitus interruptus Dominant and Ultrabithorax follow the change in engrailed. The phenotype of heatshocked HS-wg embryos resembles the segment polarity mutant naked, suggesting that embryos that overexpress wingless or lack the naked gene enter similar developmental pathways. The ubiquitous effects of ectopic wingless expression may indicate that most cells in the embryo can receive and interpret the wingless signal. For the development of the wild-type pattern, it is required that wingless is expressed in a subset of these cells. Howard Hughes Medical Institute, Stanford University, California 94305-5428. Noordermeer J J Johnston P P Rijsewijk F F Nusse R R Lawrence P A PA eng Journal Article

ENGLAND Development 8701744 IM Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Gene Expression genetics Genes, Structural, Insect genetics In Situ Hybridization Phenotype Support, Non-U.S. Gov't FBrf0047944 89030618 2903049 1988 12 22 1988 12 22 2000 12 18

0261-4189 7 10 1988 Oct Evidence that the Abdominal-B r element function is conferred by a trans-regulatory homeoprotein. 3223-31 The Abdominal-B gene is a homeotic gene located in the distal-most region of the bithorax complex (BX-C). Based on complementation analysis it has been proposed that the gene contains two separable genetic elements, called the m and r elements. The r element has a chiefly regulatory function confined to parasegment 14. In a reverse Northern screen of the distal-most BX-C DNA, we found four distinct areas that are transcribed in the embryo. One of the transcripts spans a large genomic region which, upon disruption by rearrangement breakpoints, causes loss of r element function. This transcript is expressed in the early embryo in a single domain apparently corresponding to parasegment 14. We propose that the small homeoprotein encoded by the transcript acts as a trans-regulator to confer r element function. Zoological Institute, University of Zürich, Switzerland. DeLorenzi M M Ali N N Saari G G Henry C C Wilcox M M Bienz M M eng Journal Article

ENGLAND EMBO J 8208664 0 RNA, Messenger 0 Transcription Factors IM Amino Acid Sequence Animal Cloning, Molecular Drosophila melanogaster embryology genetics Genes, Homeobox Molecular Sequence Data Nucleic Acid Hybridization RNA, Messenger genetics metabolism Restriction Mapping Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Tissue Distribution Transcription Factors genetics FBrf0125394 20142659 10678169 2000 03 09 2000 03 09 2002 11 01

1097-2765 5 1 2000 Jan Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs. 59-71 Hedgehog (HH) and Decapentaplegic (DPP) direct anteroposterior patterning in the developing Drosophila wing by functioning as short- and long-range morphogens, respectively. Here, we show that the activity of DPP is graded and is directly regulated by a novel HH-dependent mechanism. DPP activity was monitored by visualizing the activated form of Mothers against dpp (MAD), a cytoplasmic transducer of DPP signaling. We found that activated MAD levels are highest near the source of DPP but are unexpectedly low in the cells that express dpp. HH induces dpp in these cells; it also attenuates their response to DPP by downregulating expression of the DPP receptor thick veins (tkv). We suggest that regulation of tkv by HH is a key part of the mechanism that controls the level and distribution of DPP. Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan. Tanimoto H H Itoh S S ten Dijke P P Tabata T T eng Journal Article

UNITED STATES Mol Cell 9802571 0 Insect Proteins 0 Receptors, Cell Surface 0 dpp protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- DTFR protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Body Patterning Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Gene Expression Regulation, Developmental Insect Proteins physiology Morphogenesis Protein-Serine-Threonine Kinases genetics Receptors, Cell Surface genetics Signal Transduction Support, Non-U.S. Gov't Wing embryology FBrf0076617 95013378 7928386 1994 10 31 1994 10 31 2000 12 18

0018-0661 120 3 1994 Phylogenetic relationships between Drosophila subobscura, D. guanche and D. madeirensis based on Southern analysis of heat shock genes. 217-23 A Southern analysis of genomic DNA using Drosophila melanogaster probes for the major heat shock protein genes (Hsp82, Hsp70, Hsps encoding small proteins) was made to study the phylogenetic relationships between three Drosophila species belonging to the obscura group (D. subobscura, D. guanche, and D. madeirensis). The phylogenetic trees showed that D. madeirensis and D. subobscura are the most closely related species in the triad, while D. guanche is the most distantly related one. As in other Drosophila species, Hsp82 is a single copy gene in D. subobscura, D. guanche, and D. madeirensis, while Hsp70 and Hsps, which encode small proteins, are genic families. At least four sequences homologous to D. melanogaster Hsp70 were found in the obscura group species. These species have sequences which showed similarity with the four small Hsps of D. melanogaster. Departament de Genètica, Facultat de Ciències Biológiques, Universitat de València, Spain. Molto M D MD Martinez-Sebastian M J MJ De Frutos R R eng Journal Article

SWEDEN Hereditas 0374654 0 Heat-Shock Proteins IM Animal Blotting, Southern Drosophila classification genetics Drosophila melanogaster genetics Heat-Shock Proteins genetics Phylogeny Restriction Mapping Support, Non-U.S. Gov't Variation (Genetics) FBrf0048764 88232940 2897631 1988 07 07 1988 07 07 2000 12 18

0028-0836 333 6173 1988 Jun 9 Domain of Ultrabithorax expression in Drosophila visceral mesoderm from autoregulation and exclusion. 576-8 Domains of differential homeotic gene activity are formed at specific positions along the anteroposterior axis of the early Drosophila embryo. Homeotic genes are required continuously throughout development, so that homeotic gene activity has to be maintained independently of the positional information provided in the early embryo. In the ectoderm, the domains of homeotic gene activity partially overlap, but we have found that in the visceral mesoderm at least three of these genes are expressed in adjacent and mutually exclusive domains. It has been proposed that stable, sharply demarcated domains of this type could be established if a homeotic gene product stimulated its own expression locally and inhibited the expression of other homeotic genes, which Meinhardt has termed autocatalysis and mutual exclusion respectively. Furthermore, autocatalysis of this kind can in principle account for the maintenance of homeotic gene activity throughout development. We find that the unique domain of Ultrabithorax (Ubx) expression in the visceral mesoderm is dependent both on autocatalysis and on an exclusion mechanism: Ubx product is required for its own synthesis, whereas the product of the posteriorly adjacent gene abdominal-A represses Ubx expression. Zoological Institute, University of Zürich, Switzerland. Bienz M M Tremml G G eng Journal Article

ENGLAND Nature 0410462 IM Animal Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Homeobox Genes, Regulator Mesoderm physiology Morphogenesis Support, Non-U.S. Gov't FBrf0104484 98384786 9718674 1998 09 25 1998 09 25 2000 12 18

1341-7568 73 2 1998 Apr Dissection of chromosome region 89A of Drosophila melanogaster by local transposition of P elements. 95-103 In the chromosome region 89A of Drosophila melanogaster, a few meiotic genes have been suggested to exist besides c3G and rec. We carried out local mutagenesis using a strain carrying a P element-insertion (plwB) at 89A, and obtained new genetic variants. Two are female sterile mutations, an allele of the homeless locus (hls167) and a new mutation tibi (tbi), and three are lethal mutations at the serpent locus. The tbi mutation is a paternally-rescuable maternal-effect-lethal. Destabilization of the P elements revealed that these mutations were caused by P element-insertions, and produced 12 deletion lines. These lines were then used for systematic complementation test. The results showed that: (1) hls, tbi and at least three lethal genes in addition to c3G, rec and l(3)89Aa are located within the deletion of Df(3R)c3G2(89A2-3; 89A4-5); (2) the gene order is rec, tbi, hls (from centromere to telomere), and both c3G and l(3)89Aa are possibly located proximally. We cloned 117 kb of DNA from this region by plasmid rescue and chromosome walking, and mapped several of the breakpoints of the deletions. These analyses delimited the rec gene to within 21 kb of the cloned DNA, although the c3G gene could not be located on the molecular map. Department of Applied Biology, Kyoto Institute of Technology, Japan. Matsubayashi H H Yamamoto M T MT eng Journal Article

JAPAN Genes Genet Syst 9607822 0 DNA Transposable Elements IM Animal Chromosome Mapping DNA Transposable Elements Drosophila melanogaster genetics Female Gene Deletion Gene Rearrangement Genes, Insect Genetic Complementation Test Male Mutagenesis, Insertional Mutation Support, Non-U.S. Gov't Variation (Genetics) FBrf0091309 97158713 9006073 1997 02 24 1997 02 24 2000 12 18

0950-1991 124 1 1997 Jan Specification of the embryonic limb primordium by graded activity of Decapentaplegic. 125-32 Two thoracic limbs of Drosophila, the leg and the wing, originate from a common cluster of cells that include the source of two secreted signaling molecules, Decapentaplegic and Wingless. We show that Wingless, but not Decapentaplegic, is responsible for initial specification of the limb primordia with a distal identity. Limb formation is restricted to the lateral position of the embryo by negative control of the early function of Decapentaplegic and the EGF receptor homolog that determine the global dorsoventral pattern. Late function of Decapentaplegic locally determines two additional cell identities in a dosage dependent manner. Loss of Decapentaplegic activity results in a deletion of the proximal structures of the limb, which is in contrast to the consequence of decapentaplegic mutations in the imaginal disc, which cause a deletion of distal structures. The results indicate that the limb pattern elements are added in a distal to proximal direction in the embryo, which is opposite to what is happening in the growing imaginal disc. We propose that Wingless and Decapentaplegic act sequentially to initiate the proximodistal axis. Genetic Stock Research Center, National Institute of Genetics, Mishima, Japan. Goto S S Hayashi S S eng Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Membrane Proteins 0 Recombinant Fusion Proteins 0 Transforming Growth Factor beta 0 delta protein 0 dpp protein, Drosophila EC 3.2.1.23 beta-Galactosidase IM Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Extremities embryology Gene Deletion Gene Expression Regulation, Developmental In Situ Hybridization Insect Proteins biosynthesis genetics Membrane Proteins biosynthesis Recombinant Fusion Proteins biosynthesis Support, Non-U.S. Gov't Transforming Growth Factor beta physiology beta-Galactosidase biosynthesis FBrf0129772 20393997 10934032 2000 10 05 2000 11 02

0021-9533 113 ( Pt 17) 2000 Sep Do growth and cell division rates determine cell size in multicellular organisms? 2927-34 Studies in yeast have provided some clues to how cell size might be determined in unicellular eukaryotes; yet little attention has been paid to this issue in multicellular organisms. Reproducible cell sizes might be achieved in the dividing cells of multicellular organisms by the coordination of growth with cell division. Recently, mutations in genes encoding homologues of components of the mammalian insulin/phosphoinositide 3-kinase signalling pathway have been shown to affect organ growth and cell size during Drosophila melanogaster imaginal disc development. The data suggest that signalling through this pathway alters cell size because it primarily affects the growth of these organs (i.e. their increase in mass) and does not have a proportional impact on cell division. These observations are in keeping with the hypothesis that growth and cell division are regulated independently, and that cell size is just a consequence of the rate at which tissues grow and the cells within them divide. However, signalling through this pathway can affect cell cycle phasing and at least influence cell division. These interactions may provide a means of coordinating growth and cell division, such that cells divide only when they are above a minimum size. Ludwig Institute for Cancer Research, London W1P 8BT, UK. Coelho C M CM Leevers S J SJ eng Journal Article Review Review, Tutorial

ENGLAND J Cell Sci 0052457 11061-68-0 Insulin EC 2.7.1.137 1-Phosphatidylinositol 3-Kinase IM 1-Phosphatidylinositol 3-Kinase genetics physiology Animal Cell Cycle Cell Division Cell Size Drosophila melanogaster genetics physiology Insulin physiology Models, Biological Mutation Signal Transduction Translation, Genetic 64 FBrf0053399 92069758 1959135 1992 01 07 1992 01 07 2000 12 18

0092-8674 67 5 1991 Nov 29 Requirement for phosphorylation and localization of the Bicaudal-D protein in Drosophila oocyte differentiation. 917-26 In the Drosophila female the product of the germline stem cell, the cystoblast, gives rise to 16 interconnected cystocytes. One of them differentiates into the oocyte, while the 15 others become polyploid nurse cells. Bic-D is required for the differentiation of an oocyte and hence for fertility. Recessive mutations in Bic-D block the oocyte-specific accumulation of its own and other RNAs. Based on its properties and distribution, the Bic-D protein appears to be a component of a cytoskeletal transport or anchoring system. Additional results suggest that the phosphorylation of the Bic-D protein is essential for its accumulation in the pro-oocyte and that this process leads to the gradual localization to the pro-oocyte of factors required for oocyte differentiation. Department of Molecular Biology, Princeton University, New Jersey 08544. Suter B B Steward R R eng Journal Article

UNITED STATES Cell 0413066 0 Antibodies, Monoclonal 0 Insect Hormones 0 sycaudalD protein, Drosophila IM Alleles Animal Antibodies, Monoclonal Cell Differentiation Drosophila melanogaster genetics physiology Female Genes, Recessive Genes, Suppressor Immunoblotting Insect Hormones analysis genetics physiology Mutation Oocytes cytology physiology Phosphorylation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0102614 98171465 9502731 1998 06 18 1998 06 18 2002 11 01

0950-1991 125 8 1998 Apr virilizer regulates Sex-lethal in the germline of Drosophila melanogaster. 1501-7 In Drosophila, the gene Sex-lethal (Sxl) is required for female development. It controls sexual differentiation in the soma, dosage compensation and oogenesis. The continuous production of SXL proteins in XX animals is maintained by autoregulation and depends on virilizer (vir). This gene is required in somatic cells for the female-specific splicing of Sxl primary transcripts and for an unknown vital process in both sexes. In the soma, clones of XX cells lacking Sxl or vir are sexually transformed and form male structures; in the germline, XX cells mutant for Sxl extensively proliferate, but are unable to differentiate. We now studied the role of vir in the germline by generating germline chimeras. We found that XX germ cells mutant for vir, in contrast to cells mutant for Sxl, perform oogenesis. We show that the early production of SXL in undifferentiated germ cells is independent of vir while, later in oogenesis, expression of Sxl becomes dependent on vir. We conclude that the early SXL proteins are sufficient for the production of eggs whereas the later SXL proteins are dispensable for this process. However, vir must be active in the female germline to allow normal embryonic development because maternal products of vir are required for the early post-transcriptional regulation of Sxl in XX embryos and for a vital process in embryos of both sexes. Zoological Institute, University of Zürich, Zürich, Switzerland. SchüŁtt C C Hilfiker A A Nöthiger R R eng Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 0 Transcription Factors IM Animal Crosses, Genetic Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Female Gene Expression Regulation, Developmental Genes, Insect Homozygote Insect Hormones biosynthesis Male Oogenesis RNA-Binding Proteins biosynthesis genetics Sex Characteristics Sex Determination (Genetics) Support, Non-U.S. Gov't Transcription Factors metabolism X Chromosome Y Chromosome FBrf0099749 98062897 9398148 1998 01 08 1998 01 08 2002 11 01

0006-2960 36 47 1997 Nov 25 Chemical shift mapping of the RNA-binding interface of the multiple-RBD protein sex-lethal. 14306-17 The Drosophila protein Sex-lethal (Sxl) contains two RNP consensus-type RNA-binding domains (RBDs) separated by a short linker sequence. Both domains are essential for high-affinity binding to the single-stranded polypyrimidine tract (PPT) within the regulated 3' splice site of the transformer (tra) pre-mRNA. In this paper, the effect of RNA binding to a protein fragment containing both RBDs from Sxl (Sxl-RBD1 + 2) has been characterized by heteronuclear NMR. Nearly complete (85-90%) backbone resonance assignments have been obtained for unbound and RNA-bound states of Sxl-RBD1 + 2. A comparison of amide 1H and 15N chemical shifts between free and bound states has highlighted residues which respond to RNA binding. The beta-sheets in both RBDs (RBD1 and RBD2) form an RNA interaction surface, as has been observed in other RBDs. A significant number of residues display different behavior when comparing RBD1 and RBD2. This argues for a model in which RBD1 and RBD2 of Sxl have different or nonanalogous points of interaction with the tra PPT. R142 (in RBD2) exhibits the largest chemical shift change upon RNA binding. The role of R142 in RNA binding was tested by measuring the Kd of a mutant of Sxl-RBD1 + 2 in which R142 was replaced by alanine. This mutant lost the ability to bind RNA, showing a correlation with the chemical shift difference data. The RNA-binding affinities of two other mutants, F146A and T138I, were also shown to correlate with the NMR observations. Department of Chemistry, University of California at Berkeley 94720-3204, USA. Lee A L AL Volkman B F BF Robertson S A SA Rudner D Z DZ Barbash D A DA Cline T W TW Kanaar R R Rio D C DC Wemmer D E DE eng HD 28063 HD NICHD RR02301 RR NCRR Journal Article

UNITED STATES Biochemistry 0370623 0 Insect Hormones 0 RNA Precursors 0 RNA-Binding Proteins 0 Recombinant Proteins 0 Sxl protein, Drosophila IM Amino Acid Sequence Animal Base Sequence Binding Sites Comparative Study Computer Simulation Drosophila melanogaster Insect Hormones chemistry metabolism Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Magnetic Resonance, Biomolecular Protein Structure, Secondary RNA Precursors chemistry metabolism RNA-Binding Proteins chemistry metabolism Recombinant Proteins chemistry metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0051969 91065503 2123462 1991 01 14 1991 01 14 2000 12 18

0016-6731 126 3 1990 Nov deltex, a locus interacting with the neurogenic genes, Notch, Delta and mastermind in Drosophila melanogaster. 665-77 The Notch locus of Drosophila melanogaster, which codes for a transmembrane protein sharing homology with the mammalian epidermal growth factor, is one of a small number of zygotically acting genes, the so called neurogenic loci, which are necessary for the correct segregation of neural from epidermal lineages during embryogenesis. In an attempt to identify genes whose products may interact with that of Notch, we designed a genetic screen aimed at identifying suppressors of certain Notch mutations which are known to affect the extracellular epidermal growth factor homologous domain of Notch. Mutations in two neurogenic loci were identified as suppressors: Delta, whose product was recently shown to interact with Notch and mastermind. In addition, a third, X-linked gene was shown capable of acting as a suppressor. We show that this gene is the deltex locus, characterize the phenotype of deltex mutations, and demonstrate both a maternal and zygotic action of the locus. All deltex alleles behave as recessive viables affecting wing, ocellar and eye morphology. There are allele specific interactions between deltex and various Notch alleles; for example, deltex mutants with a reduced dosage of wild-type Notch die as pupae. deltex also interacts with Delta and mastermind in a fashion that is formally analogous to its interaction with Notch. These results emphasize the special relationship between Notch, Delta and mastermind suggested by previous work and indicate that deltex is likely to play an important role in the same genetic circuitry within which these three neurogenic loci operate. Howard Hughes Medical Institute, Department of Cell Biology, Yale University, New Haven, Connecticut 06511. Xu T T Artavanis-Tsakonas S S eng GM29093 GM NIGMS NS 26084 NS NINDS Journal Article

UNITED STATES Genetics 0374636 0 Membrane Proteins IM Alleles Animal Drosophila melanogaster embryology genetics Genetic Complementation Test Membrane Proteins genetics Mutation Phenotype Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Zygote metabolism FBrf0145179 21872816 11879645 2002 03 06 2002 03 29

0896-6273 33 5 2002 Feb 28 Genetic models meet trophic mechanisms: EGF family members are gliatrophins in Drosophila. 673-5 Trophic survival mechanisms are crucial for the determination of cell numbers in the developing vertebrate nervous system, but important neurotrophic factor families such as the neurotrophins have not yet been found in either Drosophila or C. elegans. Two independent studies on distinct glial populations in Drosophila have now shown that their survival is regulated by EGF family members secreted by adjacent neurons. Fly genetics thus promises new insights on trophic signaling mechanisms and confirms that trophic regulation of cell survival is an evolutionarily ancient mechanism for building the nervous system. Department of Biological Chemistry, Weizmann Institute of Science, 76100, Rehovot, Israel. Beck Gad G Fainzilber Mike M eng Journal Article Review Review, Tutorial

United States Neuron 8809320 0 Drosophila Proteins 0 Ligands 0 MAP Kinase Signaling System 0 Membrane Proteins 0 Transforming Growth Factor alpha 148175-53-5 spitz protein 62229-50-9 Epidermal Growth Factor IM Animal Cell Survival Drosophila Proteins metabolism Drosophila melanogaster genetics physiology Epidermal Growth Factor metabolism Ligands MAP Kinase Signaling System physiology Membrane Proteins genetics metabolism Neuroglia physiology Neurons metabolism Transforming Growth Factor alpha genetics metabolism 22 FBrf0149132 22038347 12021769 2002 06 03 2002 07 29 2002 11 05

1465-7392 4 6 2002 Jun Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1. 432-8 Cell death in higher organisms is negatively regulated by Inhibitor of Apoptosis Proteins (IAPs), which contain a ubiquitin ligase motif, but how ubiquitin-mediated protein degradation is regulated during apoptosis is poorly understood. Here, we report that Drosophila melanogaster IAP1 (DIAP1) auto-ubiquitination and degradation is actively regulated by Reaper (Rpr) and UBCD1. We show that Rpr, but not Hid (head involution defective), promotes significant DIAP1 degradation. Rpr-mediated DIAP1 degradation requires an intact DIAP1 RING domain. Among the mutations affecting ubiquitination, we found ubcD1, which suppresses rpr-induced apoptosis. UBCD1 and Rpr specifically bind to DIAP1 and stimulate DIAP1 auto-ubiquitination in vitro. Our results identify a novel function of Rpr in stimulating DIAP1 auto-ubiquitination through UBCD1, thereby promoting its degradation. Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University Box 252, 1230 York Ave. New York, NY 10021, USA. Ryoo Hyung Don HD Bergmann Andreas A Gonen Hedva H Ciechanover Aaron A Steller Hermann H eng R01GM60124 GM NIGMS Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Neuropeptides 0 Peptides 0 Ubiquitin 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 reaper peptide, Drosophila EC 3.4.22.- Caspases EC 6. Ligases EC 6.3.2.- ubiquitin-conjugating enzyme E2 IM Nat Cell Biol 2002 Jul;4(7):546 Age Factors Animal Apoptosis physiology Caspases metabolism Cell Count Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster Gene Expression Regulation, Developmental In Vitro Ligases genetics metabolism Mutagenesis physiology Neurons, Afferent cytology Neuropeptides genetics metabolism Peptides genetics metabolism Protein Binding physiology Protein Structure, Tertiary RNA Processing, Post-Transcriptional physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Ubiquitin metabolism FBrf0054978 91239580 1827919 1991 06 25 1991 06 25 2000 12 18

0027-8424 88 10 1991 May 15 A multimember kinesin gene family in Drosophila. 4424-7 Degenerate primers to the kinesin motor domain were used in the polymerase chain reaction to amplify DNA sequences from Drosophila genomic DNA and cDNA libraries. The amplified DNA sequences were hybridized to polytene chromosomes and the map positions of the hybridizing sites were determined. More than 30 sites of hybridization were detected, indicating that the kinesin gene family may be much larger than previously thought. One new family member has already been identified as a result of this screen. The map positions should aid in the identification of further kinesin family members. Some of these kinesin-related genes are anticipated to function in previously undiscovered roles in the cell. Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710. Endow S A SA Hatsumi M M eng GM31279 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 9007-49-2 DNA EC 3.6.1.- Kinesin EC 3.6.1.3 Adenosinetriphosphatase IM Adenosinetriphosphatase genetics physiology Amino Acid Sequence Animal Chromosomes physiology Cloning, Molecular DNA genetics Drosophila melanogaster genetics Female Gene Expression Kinesin Male Molecular Sequence Data Nucleic Acid Hybridization Polymerase Chain Reaction Sequence Homology, Nucleic Acid Support, U.S. Gov't, P.H.S. FBrf0126797 20183682 10716948 2000 04 24 2000 04 24 2000 12 18

0890-9369 14 5 2000 Mar 1 The Drosophila shark tyrosine kinase is required for embryonic dorsal closure. 604-14 Dorsal closure (DC) in the Drosophila embryo requires the coordinated interaction of two different functional domains of the epidermal cell layer-the leading edge (LE) and the lateral epidermis. In response to activation of a conserved c-Jun amino-terminal kinase (JNK) signaling module, the dorsal-most layer of cells, which constitute the LE of the stretching epithelial sheet, secrete Dpp, a member of the TGFbeta superfamily. Dpp and other LE cell-derived signaling molecules stimulate the bilateral dorsal elongation of cells of the dorsolateral epidermis over the underlaying amnioserosa and the eventual fusion of their LEs along the dorsal midline. We have found that flies bearing a Shark tyrosine kinase gene mutation, shark(1), exhibit a DC-defective phenotype. Dpp fails to be expressed in shark(1) mutant LE cells. Consistent with these observations, epidermal-specific reconstitution of shark function or overexpression of an activated form of c-Jun in the shark(1) mutant background, rescues the DC defect. Thus, Shark regulates the JNK signaling pathway leading to Dpp expression in LE cells. Furthermore, constitutive activation of the Dpp pathway throughout the epidermis fails to rescue the shark(1) DC defect, suggesting that Shark may function in additional pathways in the LE and/or lateral epithelium. Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, The Bronx, New York 10461, USA. Fernandez R R Takahashi F F Liu Z Z Steward R R Stein D D Stanley E R ER eng GM 55293 GM NIGMS P30-13330 PHS Journal Article

UNITED STATES Genes Dev 8711660 0 Insect Proteins 0 dpp protein, Drosophila 62-50-0 Ethyl Methanesulfonate EC 2.7.1.- Shark protein EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Genes Dev 2000 Apr 1;14(7):887 Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Epidermis embryology Ethyl Methanesulfonate Female Insect Proteins metabolism Male Mitogen-Activated Protein Kinases metabolism Morphogenesis physiology Mutagenesis Point Mutation Protein-Tyrosine Kinase genetics metabolism Signal Transduction Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. X Chromosome FBrf0155998 22399856 12510194 2003 01 03 2003 02 21 2003 06 16

1465-7392 5 1 2003 Jan Integrated activity of PDZ protein complexes regulates epithelial polarity. 53-8 Polarized cells contain numerous membrane domains, but it is unclear how the formation of these domains is coordinated to create a single integrated cell architecture. Genetic screens of Drosophila melanogaster embryos have identified three complexes, each containing one of the PDZ domain proteins--Stardust (Sdt), Bazooka (Baz) and Scribble (Scrib)--that control epithelial polarity and formation of zonula adherens. We find that these complexes can be ordered into a single regulatory hierarchy that is initiated by cell adhesion-dependent recruitment of the Baz complex to the zonula adherens. The Scrib complex represses apical identity along basolateral surfaces by antagonizing Baz-initiated apical polarity. The Sdt-containing Crb complex is recruited apically by the Baz complex to counter antagonistic Scrib activity. Thus, a finely tuned balance between Scrib and Crb complex activity sets the limits of the apical and basolateral membrane domains and positions cell junctions. Our data suggest a model in which the maturation of epithelial cell polarity is driven by integration of the sequential activities of PDZ-based protein complexes. Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. bilder@socrates.berkeley.edu Bilder David D Schober Markus M Perrimon Norbert N eng Journal Article

England Nat Cell Biol 100890575 0 Carrier Proteins 0 Drosophila Proteins 0 Membrane Proteins 0 Scribble protein, Drosophila 0 bazooka protein EC 2.7.4.4 Nucleoside-Phosphate Kinase EC 2.7.4.8 stardust protein, Drosophila IM Nat Cell Biol. 2003 Jan;5(1):12-4 12511884 Alleles Animal Binding Sites Carrier Proteins genetics metabolism Cell Polarity physiology Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian cytology physiology Epithelial Cells cytology physiology Membrane Proteins genetics metabolism Nucleoside-Phosphate Kinase genetics metabolism Support, Non-U.S. Gov't FBrf0149093 22045827 12049762 2002 06 06 2003 01 27

0925-4773 115 1-2 2002 Jul Wing vein formation in Drosophila melanogaster: hairless is involved in the cross-talk between Notch and EGF signaling pathways. 3-14 Wing vein development in Drosophila is controlled by different morphogenetic pathways, including Notch. Hairless (H) antagonizes Notch target gene activation by binding to the Notch signal transducer Suppressor of Hairless [Su(H)]. Accordingly, overexpression of H phenocopies reduction of Notch activity. Deletion of the Su(H)-binding domain in H-C2 results in loss of H activity. However, overexpression of H-C2 induces formation of ectopic veins. In a screen for genetic modifiers of this phenotype, we have identified several genes involved in Notch and epidermal growth factor (EGF) signaling. Most notably veinlet, an activator of EGF signaling, acts downstream of H-C2. H-C2 positively regulates veinlet maybe through inhibition of inter-vein determinants in agreement with a model, whereby Notch and EGF signaling pathways cross-regulate vein pre-patterning. Institut für Genetik (240), Universität Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany. Johannes Bernd B Preiss Anette A eng Journal Article

Ireland Mech Dev 9101218 0 Drosophila Proteins 0 Membrane Proteins 0 Transcription Factors 0 notch protein 148349-66-0 Hairless protein, Drosophila 62229-50-9 Epidermal Growth Factor IM Animal Drosophila Proteins metabolism Drosophila melanogaster growth & development metabolism Epidermal Growth Factor metabolism Membrane Proteins metabolism Morphogenesis Phenotype Signal Transduction Transcription Factors metabolism Up-Regulation Wing FBrf0049928 90128230 2515109 1990 03 15 1990 03 15 2000 12 18

0016-6731 123 4 1989 Dec Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene. 771-87 The torpedo (top) locus of Drosophila encodes the fruitfly homolog of the vertebrate epidermal growth factor receptor gene and the neu proto-oncogene. We have isolated 13 top alleles in a screen for mutations failing to complement the female sterility of top, a recessive maternal effect allele that disrupts the establishment of the dorsoventral pattern of the egg shell and embryo. Several alleles recovered in this screen are zygotic lethal mutations; genetic analysis of these alleles has demonstrated that top is allelic to the embryonic lethal locus faint little ball. The 13 mutations recovered in our screens and 19 previously isolated top alleles have been genetically characterized through complementation tests with a series of hypomorphic and amorphic alleles. Nearly every top allele fails to complement the maternal effect sterility of top. Complementation tests show that the gene is required not only for oogenesis and embryogenesis, but also for pupal viability, for the growth of certain imaginal discs and for the patterning of specific ectodermal derivatives of the imaginal discs. Complementation analysis further demonstrates that the top lesions can be divided into general phenotypic categories: alleles affecting all gene activities in a coordinate manner, alleles preferentially affecting embryogenesis, alleles preferentially retaining oogenesis activity and alleles differentially affecting the development of specific imaginal disc derivatives. Correlations observed between the various developmental defects produced by top lesions suggest that the gene possesses several differentially, though not independently, mutable activities. Biology Department, Princeton University, New Jersey 08544-1003. Clifford R J RJ Schüpbach T T eng 5 T32 GM07388-12 GM NIGMS GM40558-01 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Alleles Animal Drosophila melanogaster genetics growth & development Eye growth & development Genes, Lethal Mutation Oogenesis Phenotype Pupa Receptor, Epidermal Growth Factor genetics Support, U.S. Gov't, P.H.S. Zygote physiology FBrf0093527 97315202 9171376 1997 06 20 1997 06 20 2002 04 19

0890-9369 11 10 1997 May 15 A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. 1327-40 We present evidence that the in vivo activity of the HOX protein Antennapedia (ANTP) is modified because of phosphorylation by the serine/threonine kinase casein kinase II (CKII). Using an in vivo assay a form of ANTP that has alanine substitutions at its CKII target sites has, in addition to wild-type ANTP functions, the ability to alter severely thoracic and abdominal development. The novel functions of this protein suggest that this form of ANTP is not suppressed phenotypically by the more posterior homeotic proteins. In contrast, the in vivo activity of a form of ANTP that contains acidic amino acid substitutions at its CKII target sites, thereby mimicking a constitutively phosphorylated ANTP protein, is greatly reduced. This hypoactive form of ANTP, but not the alanine-substituted form, is also reduced in its ability to bind to DNA cooperatively with the homeodomain protein Extradenticle. Our results suggest that phosphorylation of ANTP by CKII is important for preventing inappropriate activities of this homeotic protein during embryogenesis. Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. Jaffe L L Ryoo H D HD Mann R S RS eng Journal Article

UNITED STATES Genes Dev 8711660 0 Antennapedia homeodomain protein 0 DNA-Binding Proteins 0 Genetic Markers 0 Homeodomain Proteins 9007-49-2 DNA EC 2.7.1.- casein kinase II EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Amino Acid Sequence Animal DNA metabolism DNA-Binding Proteins chemistry metabolism Drosophila melanogaster metabolism Genes, Homeobox Genetic Markers Homeodomain Proteins metabolism Molecular Sequence Data Phenotype Phosphorylation Protein Binding Protein-Serine-Threonine Kinases metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0111489 99403000 10471706 1999 10 28 1999 10 28 2000 12 18

0016-6731 153 1 1999 Sep The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. 135-77 A fundamental goal of genetics and functional genomics is to identify and mutate every gene in model organisms such as Drosophila melanogaster. The Berkeley Drosophila Genome Project (BDGP) gene disruption project generates single P-element insertion strains that each mutate unique genomic open reading frames. Such strains strongly facilitate further genetic and molecular studies of the disrupted loci, but it has remained unclear if P elements can be used to mutate all Drosophila genes. We now report that the primary collection has grown to contain 1045 strains that disrupt more than 25% of the estimated 3600 Drosophila genes that are essential for adult viability. Of these P insertions, 67% have been verified by genetic tests to cause the associated recessive mutant phenotypes, and the validity of most of the remaining lines is predicted on statistical grounds. Sequences flanking >920 insertions have been determined to exactly position them in the genome and to identify 376 potentially affected transcripts from collections of EST sequences. Strains in the BDGP collection are available from the Bloomington Stock Center and have already assisted the research community in characterizing >250 Drosophila genes. The likely identity of 131 additional genes in the collection is reported here. Our results show that Drosophila genes have a wide range of sensitivity to inactivation by P elements, and provide a rationale for greatly expanding the BDGP primary collection based entirely on insertion site sequencing. We predict that this approach can bring >85% of all Drosophila open reading frames under experimental control. Department of Embryology, Howard Hughes Medical Institute Research Laboratories, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA. spradling@mail1.ciwemb.edu Spradling A C AC Stern D D Beaton A A Rhem E J EJ Laverty T T Mozden N N Misra S S Rubin G M GM eng P50NIHHG750 HG NHGRI Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements IM Alleles Animal California Crosses, Genetic DNA Transposable Elements genetics Drosophila melanogaster genetics growth & development Expressed Sequence Tags Female Genes, Essential genetics Genes, Insect genetics Genes, Recessive genetics Genome Linkage (Genetics) genetics Male Models, Genetic Mutagenesis, Insertional Mutation genetics Phenotype Reproducibility of Results Sequence Analysis, DNA Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0076966 95107258 7808410 1995 01 30 1995 01 30 2001 11 02

0026-8925 245 5 1994 Dec 1 Mapping a mutator, mu2, which increases the frequency of terminal deletions in Drosophila melanogaster. 598-607 A mutator, mu2, in Drosophila melanogaster has been identified recently that potentiates the recovery of terminal deficiencies. The deleted chromosomes behave as if they had been capped; that is, they are protected from degradation and from fusion with other chromosome fragments. The mutator maps near the telomere on the left arm of chromosome 3. Using the selectable marker Aprt, 150 deficiencies for region 62 of the cytological map have been recovered. These deficiencies identify the map position of mu2 as 62B11-C1. A yeast artificial chromosome spanning this region has been subcloned into lambda phage, and the positions of deficiency breakpoints on either side of the mu2 gene have been identified within the subclones. These positions limit the location of the left end of the gene to a 23 kb region. In the course of these experiments, three additional, presumptive mutant alleles were identified, suggesting that other mutator alleles remain undiscovered in many standard laboratory stocks. Experimental Carcinogenesis and Mutagenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Wang M M Champion L E LE Biessmann H H Mason J M JM eng GM46211 GM NIGMS Journal Article

GERMANY Mol Gen Genet 0125036 0 Chromosomes, Artificial, Yeast 0 Genetic Markers EC 2.4.2.7 Adenine Phosphoribosyltransferase IM mu2 Adenine Phosphoribosyltransferase genetics Alleles Animal Chromosome Mapping veterinary Chromosomes, Artificial, Yeast Drosophila melanogaster genetics Female Genes, Insect Genetic Markers Male Mutation Phenotype Sequence Deletion Support, U.S. Gov't, P.H.S. Telomere genetics FBrf0049003 88145666 2830671 1988 04 07 1988 04 07 2000 12 18

0036-8075 239 4844 1988 Mar 4 Insertional mutagenesis of the Drosophila genome with single P elements. 1121-8 A versatile genetic method for identifying and cloning Drosophila melanogaster genes affecting any recognizable phenotype is described. Strains are constructed in which the insertion of a single P transposable element has caused a new mutation, greatly simplifying the genetic and molecular analysis of the affected gene. Mutagenesis is initiated by crossing two strains, each of which contains a specially designed P element. One element (jumpstarter), encoding P element transposase, efficiently mobilizes the second nonautonomous transposon (mutator), whose structure facilitates selection and cloning of new insertion mutations. Random mutator transpositions are captured in individual stocks that no longer contain jumpstarter, where they remain stable. This method was used to construct 1300 single P element insertion stocks which were then screened for recessive mutations. A library of single-element insertion strains will allow the structure and function of Drosophila genes to be readily correlated, and should have many other applications in Drosophila molecular genetics. Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210. Cooley L L Kelley R R Spradling A A eng Journal Article Review Review, Tutorial

UNITED STATES Science 0404511 0 DNA Transposable Elements 0 DNA, Recombinant 9007-49-2 DNA IM Animal Chromosomes Cloning, Molecular DNA genetics DNA Transposable Elements DNA, Recombinant Drosophila melanogaster genetics Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transformation, Genetic 45 FBrf0049353 89119561 2492450 1989 03 17 1989 03 17 2000 12 18

0092-8674 56 3 1989 Feb 10 The role of easter, an apparent serine protease, in organizing the dorsal-ventral pattern of the Drosophila embryo. 391-400 The maternally transcribed product of the Drosophila easter gene is essential for the establishment of a normal dorsal-ventral pattern in embryos. Loss-of-function mutations in easter result in a dorsalization of the embryonic pattern, while dominant gain-of-function mutations ventralize the embryonic pattern. P element insertion alleles of easter were isolated and used to identify genomic and cDNA clones that include the easter gene. Injection of in vitro-synthesized transcripts of the cDNA into embryos from easter mutant females completely rescued the mutant phenotype, allowing normal development. This result confirmed that the cDNA encodes easter and that the easter product is only required after fertilization. The sequence of the cDNA suggests that the product of the easter gene is an extracytoplasmic serine protease. The implications of the dominant alleles of this putative protease for the mechanism of dorsal-ventral pattern formation are discussed. Department of Molecular Biology, University of California, Berkeley 94720. Chasan R R Anderson K V KV eng GENBANK J03154 GM 35437 GM NIGMS Journal Article

UNITED STATES Cell 0413066 EC 3.4.21 Serine Endopeptidases IM Alleles Amino Acid Sequence Animal Base Sequence Cloning, Molecular Drosophila melanogaster embryology enzymology genetics Embryo, Nonmammalian enzymology Genes, Structural Molecular Sequence Data Mutation Phenotype Restriction Mapping Sequence Homology, Nucleic Acid Serine Endopeptidases genetics Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0055585 92191272 1547493 1992 04 22 1992 04 22 2000 12 18

0092-8674 68 5 1992 Mar 6 The primary sex determination signal of Drosophila acts at the level of transcription. 933-43 For Drosophila, the choice between male and female development is made by the switch gene, Sxl, in response to the X:A ratio. Once Sxl is turned on in females, it actively maintains the determined state, independent of the X:A signal, by a positive autoregulatory feedback loop in which Sxl proteins direct the female-specific splicing of Sxl transcripts. In this paper we have investigated the mechanism controlling pathway initiation. Our results suggest a two-step model for the initial activation of Sxl in females. In the first step, a special class of Sxl mRNAs is expressed in female embryos from an early promoter that responds to the genes signaling the X:A ratio. The proteins produced from these early mRNAs then initiate the autoregulatory loop by directing the female-specific processing of transcripts from the late Sxl promoter. Department of Biology, Princeton University, New Jersey 08544. Keyes L N LN Cline T W TW Schedl P P eng GENBANK M84162 M84163 M84182 S72766 S72767 S72768 S72769 S72771 S88324 X63098 Journal Article

UNITED STATES Cell 0413066 0 RNA, Messenger 0 Trans-Activators IM Cell 1992 May 1;69(3):following 572 Animal Base Sequence Drosophila melanogaster embryology genetics Feedback Gene Expression Regulation genetics Molecular Sequence Data RNA Splicing RNA, Messenger analysis Sequence Alignment Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators Transcription, Genetic FBrf0091164 97141928 8988178 1997 01 28 1997 01 28 2000 12 18

1061-4036 15 1 1997 Jan Low mutation rates of microsatellite loci in Drosophila melanogaster. 99-102 Analysis of variation at microsatellite DNA loci is widely used in studies of parentage, linkage and evolutionary history. The utility of microsatellites is primarily due to high levels of allelic diversity, believed to reflect mutation rates orders of magnitude higher than base pair substitutions at single-copy genes. For humans, mice, rats and pigs, microsatellite mutation rates have been estimated at 10(-3)-10(-5). However, a recent study comparing microsatellite variation in humans with non-human primates suggests that microsatellite mutation rates may vary considerably across taxa. We measured mutation rates of 24 microsatellite loci in mutation accumulation lines of Drosophila melanogaster. Surprisingly, only a single mutation was detected after screening 157,680 allele-generations, yielding an estimated average mutation rate per locus of 6.3 x 10(-6), a mutation rate considerably lower than reported for various mammals. We propose that the comparatively low mutation rate is primarily a function of short microsatellite repeat lengths in the D. melanogaster genome. Section of Genetics and Development, Cornell University, Ithaca, New York 14853, USA. Schug M D MD Mackay T F TF Aquadro C F CF eng GENBANK D13782 J01139 J03158 K03277 L07660 L07835 L32725 M14740 M17119 M19692 M26267 M31129 M32311 M64750 M72421 X02974 X03787 X52286 X52454 X53543 X58286 X72303 Z11743 GM 17872 GM NIGMS GM 36431 GM NIGMS GM 45344 GM NIGMS Journal Article

UNITED STATES Nat Genet 9216904 IM Animal Drosophila melanogaster genetics Human Microsatellite Repeats genetics Molecular Sequence Data Mutation Support, U.S. Gov't, P.H.S. FBrf0038035 83106430 6818105 1983 03 11 1983 03 11 2000 12 18

0016-6731 102 2 1982 Oct Studies on the sex-specific lethals of Drosophila melanogaster. V. Sex transformation caused by interactions between a female-specific lethal, Sxlf 1, and the male-specific lethals mle(3)132, msl-2(27), and mle. 233-43 Interactions between a female-specific lethal mutant, Sxlf 1, and each of three male-specific lethal mutants, mle(3)132, msl-2(27) and mle, of Drosophila melanogaster were observed to produce morphological changes in various sexually dimorphic external characters. Chromosomal females heterozygous for Sxlf 1 and homozygous for any one of the male-specific lethals (and to a lesser degree heterozygous for male-specific lethals) sometimes had sex combs, male-type tergites, male-type sternites, male-type anal plates or male-type external genitalia. Penetrance was not high and expression was often incomplete; single individuals never had all the sexually dimorphic structures transformed. When mothers were homozygous for male-specific lethals, higher proportions of female progeny were affected than when mothers were heterozygous, suggesting a maternal effect. Uenoyama T T Fukunaga A A Ioshi K K eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Crosses, Genetic Drosophila melanogaster genetics Female Genes, Lethal Male Recombination, Genetic Transformation, Genetic FBrf0151941 22308870 12421697 2002 11 07 2003 02 21 2003 09 29

0950-1991 129 24 2002 Dec Hephaestus encodes a polypyrimidine tract binding protein that regulates Notch signalling during wing development in Drosophila melanogaster. 5553-66 We describe the role of the Drosophila melanogaster hephaestus gene in wing development. We have identified several hephaestus mutations that map to a gene encoding a predicted RNA-binding protein highly related to human polypyrimidine tract binding protein and Xenopus laevis 60 kDa Vg1 mRNA-binding protein. Polypyrimidine tract binding proteins play diverse roles in RNA processing including the subcellular localization of mRNAs, translational control, internal ribosome entry site use, and the regulation of alternate exon selection. The analysis of gene expression in imaginal discs and adult cuticle of genetic mosaic animals supports a role for hephaestus in Notch signalling. Somatic clones lacking hephaestus express the Notch target genes wingless and cut, induce ectopic wing margin in adjacent wild-type tissue, inhibit wing-vein formation and have increased levels of Notch intracellular domain immunoreactivity. Clones mutant for both Delta and hephaestus have the characteristic loss-of-function thick vein phenotype of DELTA: These results lead to the hypothesis that hephaestus is required to attenuate Notch activity following its activation by Delta. This is the first genetic analysis of polypyrimidine tract binding protein function in any organism and the first evidence that such proteins may be involved in the Notch signalling pathway. Genes and Development Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada. Dansereau David A DA Lunke Martine D MD Finkielsztein Ariel A Russell Michael A MA Brook William J WJ eng Journal Article

England Development 8701744 0 DNA, Complementary 0 Drosophila Proteins 0 Ligands 0 Membrane Proteins 0 delta protein 0 notch protein 139076-35-0 Polypyrimidine Tract-Binding Protein IM Alleles Animal Cloning, Molecular DNA, Complementary metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics Immunohistochemistry Ligands Membrane Proteins metabolism Models, Biological Models, Genetic Mutagenesis, Site-Directed Mutation Phenotype Polypyrimidine Tract-Binding Protein genetics metabolism Protein Binding Signal Transduction Support, Non-U.S. Gov't Wing embryology FBrf0158901 22627841 12743042 2003 05 13 2003 07 14

0261-4189 22 10 2003 May 15 The Drosophila hairy RNA localization signal modulates the kinetics of cytoplasmic mRNA transport. 2484-94 In several Drosophila cell types, mRNA transport depends on microtubules, the molecular motor dynein and trans-acting factors including Egalitarian and Bicaudal-D. However, the molecular basis of transcript recognition by the localization machinery is poorly understood. Here, we characterize the features of hairy pair-rule RNA transcripts that mediate their apical localization, using in vivo injection of fluorescently labelled mRNAs into syncytial blastoderm embryos. We show that a 121-nucleotide element within the 3'-untranslated region is necessary and sufficient to mediate apical transport. The signal comprises two essential stem-loop structures, in which double-stranded stems are crucial for localization. Base-pair identities within the stems are not essential, but can contribute to the efficiency of localization, suggesting that specificity is mediated by higher-order structure. Using time-lapse microscopy, we measure the kinetics of localization and show that impaired localization of mutant signals is due to delayed formation of active motor complexes and, unexpectedly, to slower movement. These findings, and those from co-injecting wild-type and mutant RNAs, suggest that the efficiency of molecular motors is modulated by the character of their cargoes. Developmental Genetics and Light Microscopy Laboratories, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Bullock Simon L SL Zicha Daniel D Ish-Horowicz David D eng Journal Article

England EMBO J 8208664 0 Drosophila Proteins 0 Insect Proteins 0 RNA, Messenger 0 Repressor Proteins 0 egalitarian protein, Drosophila 0 sycaudalD protein, Drosophila 127385-83-5 hairy protein, insect IM Animal Base Sequence Cell Polarity Drosophila Proteins genetics metabolism Drosophila melanogaster genetics physiology Insect Proteins genetics metabolism Molecular Sequence Data Mutation Nucleic Acid Conformation Protein Transport physiology RNA, Messenger genetics metabolism Repressor Proteins genetics metabolism Sequence Alignment Support, Non-U.S. Gov't FBrf0056221 92354890 1339381 1992 09 08 1992 09 08 2003 08 07

0016-6731 131 2 1992 Jun The embryonically active gene, unkempt, of Drosophila encodes a Cys3His finger protein. 377-88 The unkempt gene of Drosophila encodes a set of embryonic RNAs, which are abundant during early stages of embryogenesis and are present ubiquitously in most somatic tissues from the syncytial embryo through stage 15 of embryogenesis. Expression of unkempt RNAs becomes restricted predominantly to the central nervous system in stages 16 and early 17. Analysis of cDNAs from this locus reveals the presence of five Cys3His fingers in the protein product. Isolation and analysis of mutations affecting the unkempt gene, including complete deletions of this gene, indicate that there is no zygotic requirement for unkempt during embryogenesis, presumably due to the contribution of maternally supplied RNA, although the gene is essential during post-embryonic development. Barnard College, New York, New York 10027. Mohler J J Weiss N N Murli S S Mohammadi S S Vani K K Vasilakis G G Song C H CH Epstein A A Kuang T T English J J eng GENBANK X12536 X61776 X61777 X61778 X61779 X61780 X61781 X66930 X66931 Z11527 R29HD22751 HD NICHD Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Nerve Tissue Proteins 0 RNA, Messenger 148411-94-3 unk protein, Drosophila IM Amino Acid Sequence Animal Base Sequence Central Nervous System embryology metabolism Consensus Sequence DNA-Binding Proteins biosynthesis genetics physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian metabolism Gene Expression Genes, Lethal Genes, Structural Molecular Sequence Data Morphogenesis Nerve Tissue Proteins biosynthesis genetics physiology Protein Conformation RNA, Messenger biosynthesis Support, U.S. Gov't, P.H.S. Zinc Fingers genetics FBrf0045776 87215934 3107840 1987 07 09 1987 07 09 2000 12 18

0092-8674 49 5 1987 Jun 5 Germ line and soma cooperate during oogenesis to establish the dorsoventral pattern of egg shell and embryo in Drosophila melanogaster. 699-707 Mutations in gurken and torpedo cause a ventralization in the follicle cell epithelium during Drosophila oogenesis and in the pattern of the embryo that develops in the resultant egg. Both genes lie midway in an epistatic series between fs(1)K10 and dorsal; the mutations block the dorsalization normally observed in K10 eggs but have no effect on the phenotype of embryos derived from dorsal mothers. Analysis of germ-line mosaics demonstrates that both ovarian and embryonic phenotypes will be produced when either the gurken+ gene is removed from the germ line or torpedo+ is removed from the soma. This shows that the dorsoventral pattern of the Drosophila egg chamber depends on the transfer of spatial information from the germ line to the somatic follicle cells, and from somatic cells to the oocyte. Schüpbach T T eng Journal Article

UNITED STATES Cell 0413066 IM Animal Chorion physiology Drosophila melanogaster embryology genetics Female Gastrula physiology Genes, Structural Mosaicism Mutation Oocytes growth & development Oogenesis Phenotype Support, U.S. Gov't, Non-P.H.S. FBrf0144897 21850431 11861560 2002 02 25 2002 05 24

0016-6731 160 2 2002 Feb Sex determination signals control ovo-B transcription in Drosophila melanogaster germ cells. 537-45 Nonautonomous inductive signals from the soma and autonomous signals due to a 2X karyotype determine the sex of Drosophila melanogaster germ cells. These two signals have partially overlapping influences on downstream sex determination genes. The upstream OVO-B transcription factor is required for the viability of 2X germ cells, regardless of sexual identity, and for female germline sexual identity. The influence of inductive and autonomous signals on ovo expression has been controversial. We show that ovo-B is strongly expressed in the 2X germ cells in either a male or a female soma. This indicates that a 2X karyotype controls ovo-B expression in the absence of inductive signals from the female soma. However, we also show that female inductive signals positively regulate ovo-B transcription in the 1X germ cells that do not require ovo-B function. Genetic analysis clearly indicates that inductive signals from the soma are not required for ovo-B function in 2X germ cells. Thus, while somatic inductive signals and chromosome karyotype have overlapping regulatory influences, a 2X karyotype is a critical germline autonomous determinant of ovo-B function in the germline. Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Andrews Justen J Oliver Brian B eng Journal Article

United States Genetics 0374636 0 DNA-Binding Proteins 0 Protein Isoforms 0 RNA, Messenger 0 Transcription Factors 0 ovo protein IM Animal DNA-Binding Proteins genetics physiology Drosophila melanogaster genetics physiology Female Gene Expression Regulation genetics physiology Germ Cells physiology Male Mutation genetics physiology Promoter Regions (Genetics) physiology Protein Isoforms genetics physiology RNA, Messenger genetics physiology Sex Determination (Genetics) Signal Transduction physiology Transcription Factors genetics physiology Transcription, Genetic physiology FBrf0149122 22010441 12015603 2002 05 16 2002 06 10 2003 06 16

0028-0836 417 6886 2002 May 16 Stress response genes protect against lethal effects of sleep deprivation in Drosophila. 287-91 Sleep is controlled by two processes: a homeostatic drive that increases during waking and dissipates during sleep, and a circadian pacemaker that controls its timing. Although these two systems can operate independently, recent studies indicate a more intimate relationship. To study the interaction between homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per(01)), timeless (tim(01)), clock (Clk(jrk)) and cycle (cyc(01)). cyc(01) mutants showed a disproportionately large sleep rebound and died after 10 hours of sleep deprivation, although they were more resistant than other clock mutants to various stressors. Unlike other clock mutants, cyc(01) flies showed a reduced expression of heat-shock genes after sleep loss. However, activating heat-shock genes before sleep deprivation rescued cyc(01) flies from its lethal effects. Consistent with the protective effect of heat-shock genes, was the observation that flies carrying a mutation for the heat-shock protein Hsp83 (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep deprivation. These data represent the first step in identifying the molecular mechanisms that constitute the sleep homeostat. The Neurosciences Institute, 10640 John J. Hopkins Drive, San Diego, California 92121, USA. Shaw Paul J PJ Tononi Giulio G Greenspan Ralph J RJ Robinson Donald F DF eng Journal Article

England Nature 0410462 0 CYCLE protein 0 Clock protein 0 Drosophila Proteins 0 Heat-Shock Proteins 0 Insect Proteins 0 Nuclear Proteins 0 PER protein, Drosophila 0 Trans-Activators 0 heat-shock protein 83 0 timeless protein, Drosophila IM Animal Circadian Rhythm genetics physiology Darkness Dehydration Drosophila Proteins genetics metabolism Drosophila melanogaster genetics physiology Female Food Deprivation Gene Expression Regulation Genes, Insect genetics Genes, Lethal genetics Heat-Shock Proteins genetics metabolism Heat-Shock Response genetics Homeostasis Insect Proteins genetics metabolism Light Mutation genetics Nuclear Proteins genetics metabolism Oxidative Stress Sleep genetics physiology Sleep Deprivation genetics mortality physiopathology Stress genetics metabolism Support, Non-U.S. Gov't Survival Rate Trans-Activators genetics metabolism Wakefulness genetics physiology FBrf0112114 99449701 10518471 1999 12 17 1999 12 17 2000 12 18

0022-0949 202 ( Pt 21) 1999 Nov Genes to remember. 2887-91 It has been known for several decades that the formation of long-term memory requires gene expression. In recent years, the use of genetic and molecular approaches has led to the identification and characterization of genes and molecules that play a fundamental role in the biological mechanisms underlying learning and memory. From these studies, it appears that molecules and molecular mechanisms essential for the process of memory have been conserved throughout evolution. The cyclic AMP (cAMP)-dependent activation pathway and a cAMP-dependent cascade of gene expression have been shown to be essential for memory formation in Aplysia californica, Drosophila melanogaster and rodents. Moreover, members of the transcription factor family cAMP response element binding proteins (CREBs) seem to represent key molecules for transforming incoming information into long-term memory. Here, we review the studies showing that conserved molecules and biological mechanisms are engaged in simple and complex forms of memory. Department of Neuroscience, Brown University, Providence, RI 02912, USA. calberini@brown.edu Alberini C M CM eng Journal Article Review Review, Tutorial

ENGLAND J Exp Biol 0243705 0 DNA-Binding Protein, Cyclic AMP-Responsive 60-92-4 Cyclic AMP EC 2.7.1.37 Protein Kinases IM Animal Cyclic AMP pharmacology DNA-Binding Protein, Cyclic AMP-Responsive genetics physiology Evolution Genetics Human Memory Mutation Protein Kinases metabolism Support, Non-U.S. Gov't 38 FBrf0053873 91114698 1671215 1991 03 01 1991 03 01 2000 12 18

0261-4189 10 1 1991 Jan Direct interaction of the Polycomb protein with Antennapedia regulatory sequences in polytene chromosomes of Drosophila melanogaster. 153-62 The Polycomb (Pc) gene is responsible for the elaboration and maintenance of the expression pattern of the homeotic genes during development of Drosophila. In mutant Pc- embryos, homeotic transcripts are ectopically expressed, leading to abdominal transformations in all segments. From this it was suggested that PC+ acts as a repressor of homeotic gene transcription. We have mapped the cis-acting control sequences of the homeotic Antennapedia (Antp) gene regulated by Pc. Using Antp P1 and P2 promoter fragments linked to the E. coli lacZ reporter gene we show different expression patterns of beta-galactosidase (beta-gal) in transformed Pc+ and Pc- embryos. In addition we are able to visualize by immunocytochemical techniques on polytene chromosomes the direct binding of the Pc protein to the transposed cis-regulatory promoter fragments. However, short Antp P1 promoter constructs which are--due to position effects--ectopically activated in salivary glands, do not reveal a Pc binding signal. Center of Molecular Biology, University of Heidelberg, FRG. Zink B B Engström Y Y Gehring W J WJ Paro R R eng Journal Article

ENGLAND EMBO J 8208664 0 Proteins 0 Recombinant Fusion Proteins 134549-01-2 Polycomb protein, insect EC 3.2.1.23 beta-Galactosidase IM Animal Chromosome Mapping Drosophila melanogaster genetics Exons Genes, Homeobox Homozygote Mutation Promoter Regions (Genetics) Protein Binding Proteins genetics Recombinant Fusion Proteins metabolism Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't beta-Galactosidase genetics metabolism FBrf0158841 22482246 12593986 2003 02 20 2003 04 18

0959-4388 13 1 2003 Feb Axon targeting in the Drosophila visual system. 90-5 The neuronal wiring of the Drosophila melanogaster visual system is constructed through an intricate series of cell-cell interactions. Recent studies have identified some of the gene regulatory and cytoskeletal signaling pathways responsible for the layer-specific targeting of Drosophila photoreceptor axons. Target selection decisions of the R1-R6 subset of photoreceptor axons have been found to be influenced by the nuclear factors Brakeless and Runt, and target selection decisions of the R7 subset of axons have been found to require the cell-surface proteins Ptp69d, Lar and N-cadherin. A role for the visual system glia in orienting photoreceptor axon outgrowth and target selection has also been uncovered. Department of Biology, 68-230 Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Tayler Timothy D TD Garrity Paul A PA eng Journal Article Review Review, Tutorial

England Curr Opin Neurobiol 9111376 IM Animal Cell Communication genetics Cell Differentiation genetics Drosophila melanogaster cytology embryology metabolism Growth Cones metabolism ultrastructure Neuroglia cytology metabolism Optic Lobe cytology embryology metabolism Photoreceptors, Invertebrate cytology embryology metabolism Signal Transduction genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Visual Pathways cytology embryology metabolism 35 FBrf0064770 93350641 8394175 1993 09 16 1993 09 16 2003 06 16

1061-4036 4 2 1993 Jun Drosophila awdK-pn, a homologue of the metastasis suppressor gene nm23, suppresses the Tum-1 haematopoietic oncogene. 195-201 The human nm23-H1 gene is a suppressor of solid tumour metastasis in some types of cancer. It is known that nm23 genes encode nucleoside diphosphate kinase polypeptides, but the regulatory pathways involving Nm23 are unclear. One approach to understanding nm23 function is to identify loci which interact with nm23. The Drosophila awd gene, a homologue of nm23, provides a model system for this genetic analysis. We report that the dominant awdK-pn allele suppresses haematopoietic defects associated with the Tum-l oncogene. Premature differentiation and aggregation of Tum-l blood cells is reduced by awdK-pn, resulting in an increased survival of Tum-l hemizygotes. Tum-l lethality is also suppressed by pn mutations, indicating the existence of a haematopoietic regulatory pathway involving the Tum-l, AwdK-pn and Pn proteins. Developmental Genetics Group, Dana Farber Cancer Institute, Boston, Massachusetts. Zinyk D L DL McGonnigal B G BG Dearolf C R CR eng Journal Article

UNITED STATES Nat Genet 9216904 0 Insect Hormones 129311-56-4 abnormal wing discs protein, Drosophila EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.4.6 Nucleoside-Diphosphate Kinase IM Tum-I awd awd<up>K-pn</up> awd<up>Killer-of-prune</up> hop nm23 nm23-H1 nm23-H2 Alleles Animal Cell Differentiation genetics Comparative Study Crosses, Genetic Drosophila melanogaster genetics growth & development Enhancer Elements (Genetics) Female Gene Expression Regulation, Neoplastic Genes, Insect Genes, Lethal Genes, Recessive Genes, Tumor Suppressor Hematopoiesis genetics Hematopoietic Stem Cells pathology Heterozygote Human Insect Hormones genetics physiology Male Neoplasm Metastasis genetics Nucleoside-Diphosphate Kinase genetics Oncogenes Phenotype Protein-Tyrosine Kinase genetics Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0127346 20266369 10805795 2000 06 13 2000 06 13 2002 11 01

0027-8424 97 10 2000 May 9 LexA chimeras reveal the function of Drosophila Fos as a context-dependent transcriptional activator. 5351-6 The transcriptional activation potential of proteins can be assayed in chimeras containing a heterologous DNA-binding domain that mediates their recruitment to reporter genes. This approach has been widely used in yeast and in transient mammalian cell assays. Here, we applied it to assay the transactivation potential of proteins in transgenic Drosophila embryos. We found that a chimera between the DNA-binding bacterial LexA protein and the transactivation domain from yeast GAL4 behaved as a potent synthetic activator in all embryonic tissues. In contrast, a LexA chimera containing Drosophila Fos (Dfos) required an unexpected degree of context to function as a transcriptional activator. We provide evidence to suggest that this context is provided by Djun and Mad (a Drosophila Smad), and that these partner factors need to be activated by signaling from Jun N-terminal kinase and decapentaplegic, respectively. Because Dfos behaves as an autonomous transcriptional activator in more artificial assays systems, our data suggest that context-dependence of transcription factors may be more prevalent than previously thought. Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. Szüts D D Bienz M M eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Bacterial Proteins 0 Chimeric Proteins 0 DNA-Binding Proteins 0 Fungal Proteins 0 GAL4 protein, S cerevisiae 0 Homeodomain Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins c-fos 0 Repressor Proteins 0 Transcription Factors 0 dpp protein, Drosophila 0 lexA protein 0 ultrabithorax protein EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase EC 3.4.21 Serine Endopeptidases IM Animal Animals, Genetically Modified Bacterial Proteins metabolism Base Sequence Chimeric Proteins metabolism DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Enhancer Elements (Genetics) Fungal Proteins genetics metabolism Homeodomain Proteins genetics Insect Proteins metabolism Mitogen-Activated Protein Kinases metabolism Proto-Oncogene Proteins c-fos metabolism Repressor Proteins metabolism Serine Endopeptidases metabolism Signal Transduction Support, Non-U.S. Gov't Trans-Activation (Genetics) Transcription Factors genetics metabolism FBrf0108296 99177176 10075933 1999 05 25 1999 05 25 2000 12 18

0261-4189 18 6 1999 Mar 15 A function of CBP as a transcriptional co-activator during Dpp signalling. 1630-41 CBP/p300 is a transcriptional co-activator that is recruited to enhancers by various DNA-binding proteins, including proteins whose activity is controlled by extracellular signals. Here, we report that Drosophila CBP loss-of-function mutants show specific defects which mimic those seen in mutants that lack the extracellular signal Dpp or its effector Mad. Furthermore, we find that CBP loss severely compromises the ability of Dpp target enhancers to respond to endogenous or exogenous Dpp. Finally, we show that CBP binds to the C-terminal domain of Mad. Our results provide evidence that CBP functions as a co-activator during Dpp signalling, and they suggest that Mad may recruit CBP to effect the transcriptional activation of Dpp-responsive genes during development. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Waltzer L L Bienz M M eng Journal Article

ENGLAND EMBO J 8208664 0 DNA-Binding Proteins 0 E1A-associated p300 protein 0 Homeodomain Proteins 0 Insect Proteins 0 Mad protein 0 Nuclear Proteins 0 Trans-Activators 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 0 ultrabithorax protein IM Animal Crosses, Genetic DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Enhancer Elements (Genetics) Female Gene Expression Regulation, Developmental Homeodomain Proteins genetics Insect Proteins genetics physiology Male Mesoderm physiology Nuclear Proteins metabolism Phenotype Recombination, Genetic Signal Transduction Support, Non-U.S. Gov't Trans-Activators metabolism Transforming Growth Factor beta physiology Viscera embryology FBrf0068418 94148222 8314084 1994 03 18 1994 03 18 2000 12 18

0890-9369 8 3 1994 Feb 1 Stripe-specific regulation of pair-rule genes by hopscotch, a putative Jak family tyrosine kinase in Drosophila. 300-12 We describe the characterization of the Drosophila gene, hopscotch (hop), which is required maternally for the establishment of the normal array of embryonic segments. In hop embryos, although expression of the gap genes appears normal, there are defects in the expression patterns of the pair-rule genes even-skipped, runt, and fushi tarazu, as well as the segment-polarity genes engrailed and wingless. We demonstrate that the effect of hop on the expression of these genes is stripe-specific. The hop gene encodes a putative nonreceptor tyrosine kinase of the Janus kinase family, based on an internal duplication of the catalytic domain. We present a model in which the Hop tyrosine kinase is involved in the control of pair-rule gene transcription in a stripe-specific manner. Our results provide the first evidence for stripe-specific regulation of pair-rule genes by a tyrosine kinase. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115. Binari R R Perrimon N N eng GENBANK L26975 Journal Article

UNITED STATES Genes Dev 8711660 0 Transcription Factors EC 2.7.1.- Hop protein EC 2.7.1.- Janus kinase 2 EC 2.7.1.112 Protein-Tyrosine Kinase IM hop Amino Acid Sequence Animal Base Sequence Comparative Study Drosophila melanogaster embryology enzymology genetics Embryo, Nonmammalian physiology Female Gene Expression Regulation, Enzymologic Genes, Lethal Genes, Structural, Insect Larva Male Molecular Sequence Data Promoter Regions (Genetics) Protein-Tyrosine Kinase chemistry genetics physiology Sequence Analysis, DNA Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics X Chromosome FBrf0057398 92350664 1386424 1992 09 02 1992 09 02 2000 12 18

0305-1048 20 14 1992 Jul 25 RNA binding specificity of a Drosophila snRNP protein that shares sequence homology with mammalian U1-A and U2-B" proteins. 3645-50 We have characterized a recombinant Drosophila melanogaster RNA binding protein, D25, by virtue of its antigenic relationship to mammalian U1 and U2 small nuclear ribonucleoprotein (U snRNP) proteins. Sequence analysis revealed that D25 bears strong similarity to both the human U1 snRNP-A (U1-A) and U2 snRNP-B" (U2-B") proteins. However, at residues known to be critical for the RNA binding specificities of U1-A and U2-B" D25 sequence is more similar to U2-B". Using direct RNA binding assays D25 selected U1 RNA from either HeLa or Drosophila Kc cell total RNA. Furthermore, D25 bound U1 RNA when transfected into mammalian cells. Thus, D25 appears to be a Drosophila homolog of the mammalian U1-A protein, despite its sequence similarity to U2-B". Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710. Harper D S DS Fresco L D LD Keene J D JD eng GENBANK M89775 GM13687-01 GM NIGMS Journal Article

ENGLAND Nucleic Acids Res 0411011 0 RNA, Small Nuclear 0 Ribonucleoproteins 0 Ribonucleoproteins, Small Nuclear 0 U1A protein IM Amino Acid Sequence Animal Blotting, Western Cloning, Molecular Drosophila melanogaster genetics metabolism Escherichia coli genetics Hela Cells Human Molecular Sequence Data RNA, Small Nuclear metabolism Ribonucleoproteins chemistry genetics metabolism Ribonucleoproteins, Small Nuclear Support, U.S. Gov't, P.H.S. FBrf0089622 96293356 8698810 1996 09 03 1996 09 03 2002 11 01

0021-9525 134 1 1996 Jul Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis. 133-48 Morphological and biochemical analyses have identified a set of proteins which together form a structure known as the adherens junction. Elegant experiments in tissue culture support the idea that adherens junctions play a key role in cell-cell adhesion and in organizing cells into epithelia. During normal embryonic development, cells quickly organize epithelia; these epithelial cells participate in many of the key morphogenetic movements of gastrulation. This prompted the hypothesis that adherens junctions ought to be critical for normal embryonic development. Drosophila Armadillo, the homologue of vertebrate beta-catenin, is a core component of the adherens junction protein complex and has been hypothesized to be essential for adherens junction function in vivo. We have used an intermediate mutant allele of armadillo, armadilloXP33, to test these hypotheses in Drosophila embryos. Adherens junctions cannot assemble in the absence of Armadillo, leading to dramatic defects in cell-cell adhesion. The epithelial cells of the embryo lose adhesion to each other, round up, and apparently become mesenchymal. Mutant cells also lose their normal cell polarity. These disruptions in the integrity of epithelia block the appropriate morphogenetic movements of gastrulation. These results provide the first demonstration of the effect of loss of adherens junctions on Drosophila embryonic development. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, 27599-3280, USA. Cox R T RT Kirkpatrick C C Peifer M M eng 5T32 GM07092 GM NIGMS Journal Article

UNITED STATES J Cell Biol 0375356 0 Actins 0 Cadherins 0 Cell Adhesion Molecules 0 Cytoskeletal Proteins 0 Membrane Proteins 0 Proteins 0 armadillo protein, Drosophila 0 crb protein, Drosophila 138930-21-9 CAP102 IM Actins metabolism Animal Cadherins metabolism Cell Adhesion Cell Adhesion Molecules physiology Cell Polarity Cytoskeletal Proteins metabolism DNA Mutational Analysis Drosophila melanogaster embryology Epithelial Cells Gastrula cytology Intercellular Junctions ultrastructure Membrane Proteins physiology Microfilaments ultrastructure Microscopy, Electron, Scanning Morphogenesis Oogenesis Proteins physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0099762 98072489 9409831 1998 02 19 1998 02 19 2000 12 18

0016-6731 147 4 1997 Dec P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F. 1697-722 We have established a collection of 2460 lethal or semi-lethal mutant lines using a procedure thought to insert single P elements into vital genes on the third chromosome of Drosophila melanogaster. More than 1200 randomly selected lines were examined by in situ hybridization and 90% found to contain single insertions at sites that mark 89% of all lettered subdivisions of the Bridges' map. A set of chromosomal deficiencies that collectively uncover approximately 25% of the euchromatin of chromosome 3 reveal lethal mutations in 468 lines corresponding to 145 complementation groups. We undertook a detailed analysis of the cytogenetic interval 86E-87F and identified 87 P-element-induced mutations falling into 38 complementation groups, 16 of which correspond to previously known genes. Twenty-one of these 38 complementation groups have at least one allele that has a P-element insertion at a position consistent with the cytogenetics of the locus. We have rescued P elements and flanking chromosomal sequences from the 86E-87F region in 35 lines with either lethal or genetically silent P insertions, and used these as probes to identify cosmids and P1 clones from the Drosophila genome projects. This has tied together the physical and genetic maps and has linked 44 previously identified cosmid contigs into seven "super-contigs" that span the interval. STS data for sequences flanking one side of the P-element insertions in 49 lines has identified insertions in the alphagamma element at 87C, two known transposable elements, and the open reading frames of seven putative single copy genes. These correspond to five known genes in this interval, and two genes identified by the homology of their predicted products to known proteins from other organisms. Department of Anatomy and Physiology, University of Dundee, United Kingdom. Deák P P Omar M M MM Saunders R D RD Pál M M Komonyi O O Szidonya J J Maróy P P Zhang Y Y Ashburner M M Benos P P Savakis C C Siden-Kiamos I I Louis C C Bolshakov V N VN Kafatos F C FC Madueno E E Modolell J J Glover D M DM eng Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 DNA, Complementary IM Alleles Animal Base Sequence Chromosome Mapping DNA Transposable Elements DNA, Complementary Drosophila melanogaster genetics Female Genes, Insect Genes, Lethal Male Mutagenesis, Insertional Restriction Mapping Support, Non-U.S. Gov't FBrf0055173 92320588 1668189 1992 08 04 1992 08 04 2000 12 18

0168-9525 7 11-12 1991 Nov-Dec Signal transduction and the fate of the R7 photoreceptor in Drosophila. 372-7 The sevenless protein tyrosine kinase receptor plays a central role in the pathway of cell fate induction that determines the development of the R7 photoreceptor in the Drosophila eye. In the last year we have learned much about the probable ligand for sevenless and have begun to dissect the signal transduction pathway that relays the information from the sevenless kinase. Studies of the mechanisms governing the specificity of signal transmission and reception suggest that the sevenless signal directs a bipotential cell towards a neuronal rather than a cone cell fate. Howard Hughes Medical Institute, University of California, Berkeley 94720. Rubin G M GM eng Journal Article Review Review, Tutorial

ENGLAND Trends Genet 8507085 0 Eye Proteins 0 Membrane Glycoproteins 0 Membrane Proteins 0 Receptors, Cell Surface 0 Recombinant Fusion Proteins 0 bride of sevenless protein 0 sevenless protein EC 2.7.1.112 Protein-Tyrosine Kinase IM N<up>spl</up> Rap1 Ras1 Sos boss hsp-70 let-23 rap1/Krev sev sina Animal Drosophila melanogaster physiology Eye growth & development Eye Proteins genetics physiology Gene Expression Regulation Genes, Structural Membrane Glycoproteins genetics physiology Membrane Proteins genetics physiology Models, Genetic Photoreceptors metabolism Protein-Tyrosine Kinase genetics physiology Receptors, Cell Surface genetics physiology Recombinant Fusion Proteins biosynthesis Signal Transduction Suppression, Genetic 32 FBrf0037133 82057917 6795495 1982 01 28 1982 01 28 2000 12 18

0027-5107 81 3 1981 May Genetic analysis of X-linked mutagen-sensitive mutants of Drosophila melanogaster. 329-43 Mutants at 2 new loci which control mutagen-sensitivity are described. Mutants of both foci are female-sterile and are hypersensitive to killing by MMS; neither increases the frequency of sex-linked recessive lethals. A screen of previously described female-sterile and meiotic mutants has revealed that a number of these are also sensitive to mutagens. In addition, several new mutants have been identified on the basis of sensitivity to either HN2 or MMS. An analysis of complementation data suggests that all of the X-linked genes controlling sensitivity to MMS may now have been identified. Among the new mei-41 alleles are mutants which show very little meiotic nondisjunction or loss. Cytogenetic mapping of previously known mutants is also described. The mutants mus(1)104D1 and mei-41D5 are located in the region 14B13+/- -14D1,2 on the polytene chromosome map, and they map very close to each other genetically. Cytogenetically mus(1)101D1 is between salivary chromosome bands 12A6,7 and 12D3, mus(1)103D1 is between bands 12A1,2 and 12A6,7 and mus(1)109A1 is in section 8F3--9A2. Mason J M JM Green M M MM Shaw K E KE Boyd J B JB eng GM 22221 GM NIGMS Journal Article

NETHERLANDS Mutat Res 0400763 0 Mitogens IM Animal Chromosome Mapping Drosophila melanogaster genetics Drug Resistance Female Genes, Structural Infertility, Female genetics Linkage (Genetics) Mitogens pharmacology Mutation Sex Chromosomes Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. X Chromosome FBrf0098834 97476318 9335604 1997 12 08 1997 12 08 2002 11 08

0016-6731 147 2 1997 Oct Mobile element 297 in the Abd-B gene of Drosophila melanogaster, not Delta 88, is responsible for the tuh-3 mutation. 679-88 The tumorous-head-3 (tuh-3) mutation has been associated with the insertion of mobile element Delta 88 at +200 on the bithorax complex (BX-C) DNA map, 5' of all Abdominal-B (Abd-B) transcripts. Different phenotypes of tuh-3 are regulated by the tumorous-head-1 (tuh-1) maternal effect locus. In the presence of the recessive tuh-1h maternal effect, tuh-3 offspring produce homeotic abdominal and genital tissue in the head. In the presence of the dominant tuh-1g maternal effect, tuh-3 offspring have normal heads but now show genital defects. One other mutant, I127B, produces flies with identical defects to that of tuh-3 in the presence of both maternal effects. Molecular analysis of I127B revealed the insertion of mobile element 297 in the Abd-B gene, approximately 25 kb downstream of the Delta 88 insertion in tuh-3. No other abnormalities were detected. Reexamination of our tuh-3 strain revealed a 297 insertion in an identical region to that of I127B, in addition to the Delta 88 insertion. Recombinants of tuh-3, carrying 297 only, produced homeotic head defects and genital defects in the presence of the tuh-1h and tuh-1g maternal effects, respectively. Recombinants of tuh-3, carrying Delta 88 only, failed to produce any defects in the presence of either maternal effect. Based upon these results, we propose that it is the 297 insertion in the Abd-B gene, not Delta 88, that is responsible for the tuh-3 mutation. Department of Biology, University of Central Florida, Orlando 32816, USA. mack@cmgm.stanford.edu. Mack J A JA Smith R D RD Kuhn D T DT eng Journal Article

UNITED STATES Genetics 0374636 0 Abd-B proteins, Drosophila 0 DNA Transposable Elements 0 Homeodomain Proteins 9007-49-2 DNA IM Animal Base Sequence Cloning, Molecular DNA DNA Transposable Elements Drosophila melanogaster genetics Female Genomic Imprinting Homeodomain Proteins genetics Male Molecular Sequence Data Mutation Recombination, Genetic Support, U.S. Gov't, Non-P.H.S. FBrf0100065 98078701 9418892 1998 01 22 1998 01 22 2000 12 18

0270-7306 18 1 1998 Jan Regulation of sex-specific selection of fruitless 5' splice sites by transformer and transformer-2. 450-8 In Drosophila melanogaster, the fruitless (fru) gene controls essentially all aspects of male courtship behavior. It does this through sex-specific alternative splicing of the fru pre-mRNA, leading to the production of male-specific fru mRNAs capable of expressing male-specific fru proteins. Sex-specific fru splicing involves the choice between alternative 5' splice sites, one used exclusively in males and the other used only in females. Here we report that the Drosophila sex determination genes transformer (tra) and transformer-2 (tra-2) switch fru splicing from the male-specific pattern to the female-specific pattern through activation of the female-specific fru 5' splice site. Activation of female-specific fru splicing requires cis-acting tra and tra-2 repeat elements that are part of an exonic splicing enhancer located immediately upstream of the female-specific fru 5' splice site and are recognized by the TRA and TRA-2 proteins in vitro. This fru splicing enhancer is sufficient to promote the activation by tra and tra-2 of both a 5' splice site and the female-specific doublesex (dsx) 3' splice site, suggesting that the mechanisms of 5' splice site activation and 3' splice site activation may be similar. Department of Biological Sciences, Stanford University, California 94305-5020, USA. vheinric@cmgm.stanford.edu Heinrichs V V Ryner L C LC Baker B S BS eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Nerve Tissue Proteins 0 Ribonucleoproteins 0 Transcription Factors 0 fruitless protein 0 transformer-2 protein IM Animal Drosophila melanogaster genetics Female Gene Expression Regulation Genes, Insect Male Nerve Tissue Proteins genetics RNA Splicing Ribonucleoproteins genetics Sex Factors Support, U.S. Gov't, P.H.S. Transcription Factors genetics FBrf0127351 20221548 10757786 2000 05 15 2000 05 15 2002 11 01

0270-7306 20 9 2000 May TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development. 3015-26 Transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK superfamily and has been characterized as a component of the TGF-beta/bone morphogenetic protein signaling pathway. TAK1 function has been extensively studied in cultured cells, but its in vivo function is not fully understood. In this study, we isolated a Drosophila homolog of TAK1 (dTAK1) which contains an extensively conserved NH(2)-terminal kinase domain and a partially conserved COOH-terminal domain. To learn about possible endogenous roles of TAK1 during animal development, we generated transgenic flies which express dTAK1 or the mouse TAK1 (mTAK1) gene in the fly visual system. Ectopic activation of TAK1 signaling leads to a small eye phenotype, and genetic analysis reveals that this phenotype is a result of ectopically induced apoptosis. Genetic and biochemical analyses also indicate that the c-Jun amino-terminal kinase (JNK) signaling pathway is specifically activated by TAK1 signaling. Expression of a dominant negative form of dTAK during embryonic development resulted in various embryonic cuticle defects including dorsal open phenotypes. Our results strongly suggest that in Drosophila melanogaster, TAK1 functions as a MAPKKK in the JNK signaling pathway and participates in such diverse roles as control of cell shape and regulation of apoptosis. Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan. Takatsu Y Y Nakamura M M Stapleton M M Danos M C MC Matsumoto K K O'Connor M B MB Shibuya H H Ueno N N eng GENBANK AF199466 GM47462 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Plasmids 0 Transforming Growth Factor beta EC 2.7.1.- MAPK kinase kinase 7 EC 2.7.1.37 MAP Kinase Kinase Kinases EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Amino Acid Sequence Animal Animals, Genetically Modified Apoptosis Drosophila embryology Eye embryology Genes, Dominant MAP Kinase Kinase Kinases genetics physiology Mice Microscopy, Electron, Scanning Mitogen-Activated Protein Kinases metabolism Molecular Sequence Data Phenotype Phosphorylation Phylogeny Plasmids Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transforming Growth Factor beta metabolism FBrf0151530 21930744 11932008 2002 04 04 2002 10 08 2003 08 29

0168-9525 18 4 2002 Apr New alleles of Notch draw a blueprint for multifunctionality. 168-70 The Drosophila Notch protein is one of a family of receptors that mediate an essential and perhaps universal function in the assignation of cell fates during development. Activation of Notch by its ligand, Delta, leads to the cleavage of the intracellular domain of the receptor. This domain relocates to the nucleus, where it combines with the transcription factor Suppressor of Hairless to regulate gene expression. In a recent report, Ramain, Heitzler and colleagues reveal the existence of a second Notch signalling activity that is independent of Suppressor of Hairless and might be used to link Notch activity to that of other signalling pathways, most notably Wingless/Wnt signalling. This link might be a central element in many processes of cell-fate assignation during development. Dept of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. ama11@cus.cam.ac.uk Arias Alfonso Martinez AM eng Journal Article

England Trends Genet 8507085 0 Membrane Proteins 0 Repressor Proteins 0 notch protein 0 suppressor of Hairless protein, Drosophila IM Alleles Animal Drosophila melanogaster embryology genetics Epistasis, Genetic Gene Deletion Gene Expression Regulation physiology Membrane Proteins genetics Multigene Family genetics physiology Repressor Proteins physiology Signal Transduction FBrf0064592 94073971 8252628 1994 01 10 1994 01 10 2002 11 08

0092-8674 75 5 1993 Dec 3 The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye. 927-38 Cell-type specification in the Drosophila compound eye begins at the morphogenetic furrow. The furrow sweeps across the developing eye epithelium and is coincident with four classes of cellular events: coordinated changes in cell shape, changes in gene expression, synchronization of the cell cycle, and the specification of a regular array of ommatidial founder cells. The molecular mechanisms that induce these events in the developing eye have hitherto been unknown. We identify here a gene specifically required for furrow progression, hedgehog (hh). We show that hh expression posterior to the morphogenetic furrow is continuously required for its progression. We propose that forward diffusion of hh protein induces anterior cells to enter the furrow. Department of Biological Sciences, University of Southern California, Los Angeles 90089. Ma C C Zhou Y Y Beachy P A PA Moses K K eng 1RO1EYO922-02 EY NEI Journal Article

UNITED STATES Cell 0413066 0 Insect Hormones 0 Membrane Proteins 0 Proteins 0 RNA, Messenger 0 patched protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Drosophila melanogaster embryology Eye embryology Female Gene Expression Genes, Dominant Genes, Structural, Insect Genes, Suppressor Insect Hormones physiology Membrane Proteins physiology Morphogenesis Mosaicism Photoreceptors, Invertebrate embryology Proteins physiology RNA, Messenger genetics Retina embryology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0141562 21601152 11735223 2001 12 12 2002 02 21 2002 11 01

0888-7543 78 3 2001 Dec Comparative genomic sequence analysis of the FXR gene family: FMR1, FXR1, and FXR2. 169-77 Mutations in the X-linked gene FMR1 cause fragile X syndrome, the leading cause of inherited mental retardation. Two autosomal paralogs of FMR1 have been identified, and are known as FXR1 and FXR2. Here we describe and compare the genomic structures of the mouse and human genes FMR1, FXR1, and FXR2. All three genes are very well conserved from mouse to human, with identical exon sizes for all but two FXR2 exons. In addition, the three genes share a conserved gene structure, suggesting they are derived from a common ancestral gene. As a first step towards exploring this hypothesis, we reexamined the Drosophila melanogaster gene Fmr1, and found it to have several of the same intron/exon junctions as the mammalian FXRs. Finally, we noted several regions of mouse/human homology in the noncoding portions of FMR1 and FXR1. Knowledge of the genomic structure and sequence of the FXR family of genes will facilitate further studies into the function of these proteins. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Kirkpatrick L L LL McIlwain K A KA Nelson D L DL eng GM52982 GM NIGMS HD24064 HD NICHD HD29256 HD NICHD HD38038 HD NICHD Journal Article

United States Genomics 8800135 0 3' Untranslated Regions 0 Chromosomes, Artificial, Bacterial 0 FXR1 protein, human 0 FXR2 protein, human 0 Nerve Tissue Proteins 0 RNA-Binding Proteins 139135-51-6 FMR-1 protein 9007-49-2 DNA IM 3' Untranslated Regions Animal Base Sequence Chromosomes, Artificial, Bacterial Comparative Study DNA Exons Human Introns Mice Molecular Sequence Data Multigene Family Nerve Tissue Proteins genetics Promoter Regions (Genetics) RNA-Binding Proteins genetics Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome FBrf0099018 98033249 9367426 1997 12 11 1997 12 11 2000 12 18

0950-1991 124 19 1997 Oct The roles of hedgehog and engrailed in patterning adult abdominal segments of Drosophila. 3703-14 We present evidence that hedgehog (hh) protein secreted by posterior compartment cells plays a key role in patterning the posterior portion of the anterior compartment in adult abdominal segments. Loss of function of hh in the hh(ts2) mutant causes the loss of posterior tergite characteristics in the anterior compartment, whereas ectopic expression driven by hs-hh or the gain-of-function allele hh(Mir) causes transformation of anterior structures toward the posterior. FLP-out hh-expressing clones in the anterior compartment induce surrounding wild-type cells to produce posterior tergite structures, establishing that hh functions nonautonomously. The effects of pulses of ectopic expression driven by hs-hh indicate that bristle type and pigmentation are patterned by hh at widely different times in pupal development. We also present evidence that the primary polarization of abdominal segments is symmetric. This symmetry is strikingly revealed by ectopic expression of engrailed (en). As expected, this transforms anterior compartment cells to posterior compartment identity. In addition, however, ectopic en expression causes an autonomous reversal of polarity in the anterior portion of the anterior compartment, but not the posterior portion. By determining the position of polarity reversal within en-expressing clones, we were able to define a cryptic line of symmetry that lies within the pigment band of the normal tergite. This line appears to be retained in hh(ts2) mutants raised at the restrictive temperature, suggesting it is not established by hh signaling. We argue that the primary role of hh in controlling polarity is to cause anterior compartment cells to reverse their interpretation of an underlying symmetric polarization. Consistent with this, we find that strong ectopic expression of hh causes mirror-symmetric double posterior patterning, whereas hh loss of function can cause mirror-symmetric double anterior patterning. Department of Biology, Washington University, St Louis, MO 63130, USA. Kopp A A Muskavitch M A MA Duncan I I eng GM32318 GM NIGMS SO7 RR07031 RR NCRR Journal Article

ENGLAND Development 8701744 0 Homeodomain Proteins 0 Insect Proteins 0 engrailed protein 149291-21-4 hedgehog protein, Drosophila IM Abdomen Animal Body Patterning Drosophila melanogaster anatomy & histology genetics Epidermis physiology Gene Expression Regulation, Developmental Heat Homeodomain Proteins biosynthesis physiology Insect Proteins biosynthesis physiology Phenotype Pupa Support, U.S. Gov't, P.H.S. FBrf0054677 91260708 1710769 1991 07 17 1991 07 17 2000 12 18

0270-7306 11 7 1991 Jul The complex set of late transcripts from the Drosophila sex determination gene sex-lethal encodes multiple related polypeptides. 3584-602 Sex-lethal (Sxl), a key sex determination gene in Drosophila melanogaster, is known to express a set of three early transcripts arising during early embryogenesis and a set of seven late transcripts occurring from midembryogenesis through adulthood. Among the late transcripts, male-specific mRNAs were distinguished from their female counterparts by the presence of an extra exon interrupting an otherwise long open reading frame (ORF). We have now analyzed the structures of the late Sxl transcripts by cDNA sequencing, Northern (RNA) blotting, primer extension, and RNase protection. The late transcripts appear to use a common 5' end but differ at their 3' ends by the use of alternative polyadenylation sites. Two of these sites lack canonical AATAAA sequences, and their use correlates in females with the presence of a functional germ line, suggesting possible tissue-specific polyadenylation. Besides the presence of the male-specific exon, no additional sex-specific splicing events were detected, although a number of non-sex-specific splicing variants were observed. In females, the various forms of late Sxl transcript potentially encode up to six slightly different polypeptides. All of the protein-coding differences occur outside the previously defined ribonucleoprotein motifs. One class of Sxl mRNAs also includes a second long ORF in the same frame as the first ORF but separated from it by a single ochre codon. The function of this second ORF is unknown. Significant amounts of apparently partially processed Sxl RNAs were observed, consistent with the hypothesis that the regulated Sxl splices occur relatively slowly. Department of Molecular Biology, Princeton University, New Jersey 08544. Samuels M E ME Schedl P P Cline T W TW eng GENBANK D00651 D00652 D00653 D00654 M59447 M59448 M63851 M64825 M64826 M64827 Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Oligonucleotide Probes 0 RNA, Messenger 24937-83-5 Poly A 63231-63-0 RNA 9007-49-2 DNA IM Sxl Amino Acid Sequence Animal Base Sequence Blotting, Northern DNA genetics isolation & purification Drosophila melanogaster genetics physiology Female Gene Library Genes, Lethal Male Molecular Sequence Data Oligonucleotide Probes Open Reading Frames Poly A genetics isolation & purification RNA genetics isolation & purification RNA, Messenger genetics Restriction Mapping Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Translation, Genetic FBrf0080497 95226383 7711018 1995 05 17 1995 05 17 2000 12 18

0006-2960 34 15 1995 Apr 18 Comparison of the signaling abilities of the Drosophila and human insulin receptors in mammalian cells. 4962-8 Chimeric receptors encoding either the whole or a portion of the cytoplasmic domain of the drosophila insulin receptor (IR) with the extracellular domain of the human IR were expressed either transiently in COS cells or stably in Chinese hamster ovary cells and compared with the wild-type human IR. All three receptors bound insulin equally and exhibited an insulin-activated tyrosine kinase activity. The ability of the drosophila cytoplasmic domain to mediate the tyrosine phosphorylation of insulin receptor substrate 1, stimulate cell proliferation, and activate MAP kinase was found to be indistinguishable from that of the human IR. The chimeric drosophila receptors did not bind more phosphatidylinositol 3-kinase than the human IR, despite containing a C-terminal extension with potential tyrosine phosphorylation sites in the motif recognized by the SH2 domain of this enzyme. Thus, the essential signal-transducing abilities of the IR appear to have been conserved from invertebrates to mammals, despite the considerable differences in the sequences of these receptors. Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305, USA. Yamaguchi T T Fernandez R R Roth R A RA eng DK 34926 DK NIDDK DK 41765 DK NIDDK Journal Article

UNITED STATES Biochemistry 0370623 0 Chimeric Proteins 0 DNA, Complementary EC 2.7.1.112 Receptor, Insulin IM Animal Base Sequence CHO Cells Cell Line Chimeric Proteins biosynthesis Comparative Study Cricetulus DNA, Complementary Drosophila melanogaster chemistry Enzyme Activation Hamsters Human Immunoblotting Molecular Sequence Data Precipitin Tests Radioligand Assay Receptor, Insulin biosynthesis metabolism physiology Signal Transduction physiology Species Specificity Support, U.S. Gov't, P.H.S. FBrf0058083 93321590 8330518 1993 08 17 1993 08 17 2000 12 18

0950-1991 117 2 1993 Feb Specifying the path of the intersegmental nerve of the Drosophila embryo: a role for Delta and Notch. 431-40 The intersegmental nerve (ISN) of the Drosophila embryo follows a reproducible course near the anterior border of each segment. Based on the experiments reported here, we suggest that growth of the axons constituting the nerve is guided, in part, by the transmembrane proteins Delta and Notch. In particular, we suggest that expression of Delta protein on a branch of the trachea provides a path for the nerve through the lateral part of the embryo, and that the growing axons use the Notch protein on their surfaces to recognize this path. Consistent with this idea, we show that disruption of the trachea abolishes the ability of the ISN to extend through this part of the embryonic periphery. Finally, we argue that the same regulatory network that directs these peripheral axons also specifies the trajectory of part of the axonal scaffold of the central nervous system. Howard Hughes Medical Institute, University of California, San Francisco 94143. Giniger E E Jan L Y LY Jan Y N YN eng Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 Membrane Proteins 0 delta protein 0 notch protein IM Animal Axons ultrastructure Central Nervous System embryology Drosophila melanogaster embryology Insect Hormones physiology Membrane Proteins physiology Mutation physiology Peripheral Nerves embryology ultrastructure Support, Non-U.S. Gov't FBrf0131402 20530495 11076763 2001 02 02 2001 02 02 2001 11 02

0950-1991 127 24 2000 Dec DRacGAP, a novel Drosophila gene, inhibits EGFR/Ras signalling in the developing imaginal wing disc. 5427-38 We have identified a novel Drosophila gene, DRacGAP, which behaves as a negative regulator of &Rgr;-family GTPases DRac1 and DCdc42. Reduced function of DRacGAP or increased expression of DRac1 in the wing imaginal disc cause similar effects on vein and sensory organ development and cell proliferation. These effects result from enhanced activity of the EGFR/Ras signalling pathway. We find that in the wing disc, DRac1 enhances EGFR/Ras-dependent activation of MAP Kinase in the prospective veins. Interestingly, DRacGAP expression is negatively regulated by the EGFR/Ras pathway in these regions. During vein formation, local DRacGAP repression would ensure maximal activity of Rac and, in turn, of Ras pathways in vein territories. Additionally, maximal expression of DRacGAP at the vein/intervein boundaries would help to refine the width of the veins. Hence, control of DRacGAP expression by the EGFR/Ras pathway is a previously undescribed feedback mechanism modulating the intensity and/or duration of its signalling during Drosophila development. Centro de Biología Molecular Severo Ochoa, CSIC and UAM Cantoblanco, Spain. Sotillos S S Campuzano S S eng Journal Article

ENGLAND Development 8701744 0 DNA Primers 0 GTPase-Activating Proteins EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 3.6.1.- ras Proteins IM Amino Acid Sequence Animal Animals, Genetically Modified Apoptosis genetics Base Sequence Cell Cycle genetics Cell Division genetics DNA Primers genetics Drosophila melanogaster genetics growth & development metabolism GTPase-Activating Proteins genetics Gene Expression Regulation, Developmental Genes, Insect Lac Operon Models, Biological Molecular Sequence Data Mutagenesis, Site-Directed Receptor, Epidermal Growth Factor metabolism Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Wing growth & development ras Proteins metabolism FBrf0147184 22002189 12006672 2002 05 13 2002 05 22 2003 01 22

1531-2267 9 2 2002 Programmed cell death takes flight: genetic and genomic approaches to gene discovery in Drosophila. 59-69 Programmed cell death (PCD) is an essential and wide-spread physiological process that results in the elimination of cells. Genes required to carry out this process have been identified, and many of these remain the subjects of intense investigation. Here, we describe PCD, its functions, and some of the consequences when it goes awry. We review PCD in the model system, the fruit fly, Drosophila melanogaster, with a particular emphasis on cell death gene discovery resulting from both genetics and genomics-based approaches. Genome Sequence Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6. sgorski@bcgsc.bc.ca Gorski S S Marra M M eng Journal Article Review Review, Academic

United States Physiol Genomics 9815683 IM Animal Apoptosis genetics physiology Drosophila melanogaster cytology genetics Evolution Gene Expression Profiling Genes, Insect Genome Human Models, Biological Support, Non-U.S. Gov't 157 FBrf0084085 96074618 7479910 1995 12 28 1995 12 28 2000 12 18

0027-8424 92 24 1995 Nov 21 Activated Drosophila Ras1 is selectively suppressed by isoprenyl transferase inhibitors. 10919-23 Ras CAAX (C = cysteine, A = aliphatic amino acid, and X = any amino acid) peptidomimetic inhibitors of farnesyl protein transferase suppress Ras-dependent cell transformation by preventing farnesylation of the Ras oncoprotein. These compounds are potential anticancer agents for tumors associated with Ras mutations. The peptidomimetic FTI-254 was tested for Ras1-inhibiting activity in whole animals by injection of activated Ras1val12 Drosophila larvae. FTI-254 decreased the ability of Ras1val12 to form supernumerary R7 photoreceptor cells in the compound eye of transformed flies. In contrast, it had no effect on the related supernumerary R7 phenotypes of flies transformed with either the activated sevenless receptor tyrosine kinase, Raf kinase, or a chimeric Ras1val12 protein that is membrane associated through myristylation instead of isoprenylation. Therefore, FTI-254 acts as an isoprenylation inhibitor to selectively inhibit Ras1val12 signaling activity in a whole-animal model system. Department of Biological Sciences, University of Pittsburgh, PA 15260, USA. Kauffmann R C RC Qian Y Y Vogt A A Sebti S M SM Hamilton A D AD Carthew R W RW eng CA55823 CA NCI EY10111 EY NEI Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Enzyme Inhibitors 0 Oligopeptides EC 2. Transferases EC 2.5.1.29 farnesyltranstransferase EC 3.6.1.- Proto-Oncogene Protein p21(ras) IM Amino Acid Sequence Animal Drosophila melanogaster anatomy & histology Enzyme Inhibitors pharmacology Eye Abnormalities etiology Molecular Sequence Data Oligopeptides pharmacology Proto-Oncogene Protein p21(ras) antagonists & inhibitors physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transferases antagonists & inhibitors physiology FBrf0096169 97386448 9244297 1997 08 28 1997 08 28 2002 04 19

0092-8674 90 2 1997 Jul 25 Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. 225-34 The hedgehog gene of Drosophila melanogaster encodes a secreted protein (HH) that plays a vital role in cell fate and patterning. Here we describe a protein complex that mediates signal transduction from HH. The complex includes the products of at least three genes: fused (a protein-serine/threonine kinase), cubitus interruptus (a transcription factor), and costal2 (a kinesin-like protein). The complex binds with great affinity to microtubules in the absence of HH, but binding is reversed by HH. Mutations in the extracatalytic domain of FU abolish both the biological function of the protein and its association with COS2. We conclude that the complex may facilitate signaling from HH by governing access of the cubitus interruptus protein to the nucleus. G.W. Hooper Foundation and Department of Microbiology and Immunology, University of California, San Francisco, 94143-0552, USA. Robbins D J DJ Nybakken K E KE Kobayashi R R Sisson J C JC Bishop J M JM Thérond P P PP eng CA44338 CA NCI CA45508 CA NCI Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 Insect Proteins 0 costal2 protein 0 cubitus interruptus protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 3.6.1.- Kinesin IM Amino Acid Sequence Animal Cells, Cultured DNA-Binding Proteins genetics metabolism Drosophila melanogaster chemistry growth & development physiology Embryo, Nonmammalian chemistry physiology Gene Expression Regulation, Developmental physiology Insect Proteins genetics metabolism Kinesin genetics metabolism pharmacology Microtubules metabolism Phosphorylation Protein Binding physiology Protein Structure, Tertiary Protein-Serine-Threonine Kinases chemistry genetics metabolism Signal Transduction physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zinc Fingers genetics FBrf0037137 82125161 6799811 1982 04 12 1982 04 12 2000 12 18

0027-5107 83 3 1981 Oct Differences in the induction of specific deletions and duplications by two male recombination factors isolated from the same Drosophila natural population. 383-93 2 male recombination factors, the 31.1 and 23.5 MRF isolated from the same natural population, were tested for the induction of specific deletions and duplications in the regions b and cn of the second chromosome. Genetic and cytological analysis of the double recombinants derived from appropriate crosses of the 23.5/CyL4 and 31.1/CyL4 strains with the dp b cn bw; ve revealed the following differences between the 2 MRFs. (1) The 23.5 MRF induced (a) higher frequencies of double "putative' recombinants, which often appeared in large clusters, (b) large clusters of single recombinants and (c) cases were the wild-type and sometimes the dp b cn bw phenotype were not produced among the F2-F10 progeny. Such cases were never found with 31.1 MRF. (2) The b and cn recombinants carried deletions whereas the reciprocal dp cn bw and dp b bw had duplications of the corresponding regions. Each cluster carried an identical deletion or duplication. (3) The breakpoints of the 22 cn deletions detected were distributed in the polytene region 42E-44C. On the basis of the cn deletions, we mapped the cn and so loci to polytene intervals 43E6-16 and 42E3.4--43C5.6, respectively. Hypotheses explaining the different results obtained by the 2 factors are discussed. Yannopoulos G G Stamatis N N Zacharopoulou A A Pelecanos M M eng Journal Article

NETHERLANDS Mutat Res 0400763 IM Animal Chromosome Deletion Chromosome Mapping Chromosomes ultrastructure DNA Replication Drosophila melanogaster genetics Male Phenotype Recombination, Genetic Sex Factors FBrf0082580 95324812 7601354 1995 08 07 1995 08 07 2003 03 28

0890-9369 9 12 1995 Jun 15 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. 1518-29 The spitz gene encoding a TGF-alpha homolog, has been shown to affect a subset of developmental processes that are similar to those regulated by DER, the Drosophila EGF receptor homolog. This work demonstrates that Spitz triggers the DER signaling cascade. Addition of a secreted, but not the membrane-associated form of Spitz to S2 Drosophila cells expressing DER gives rise to a rapid tyrosine autophosphorylation of DER. Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. The profile of MAP kinase activation provides a quantitative assay for DER activation. A dose response between the levels of Spitz and MAP kinase activity was observed. The secreted Spitz protein was expressed in embryos to assess its biological activity. An alteration in cell fates was observed in the ventral ectoderm, such that lateral cells acquired the ventral-most fates. The result indicates that graded activation of the DER pathway may normally give rise to a repertoire of discrete cell fates in the ventral ectoderm. Spatially restricted processing of Spitz may be responsible for this graded activation. The Rhomboid (Rho) and Star proteins were suggested, on the basis of genetic interactions, to act as modulators of DER signaling. No alteration in DER autophosphorylation or the pattern of MAP kinase activation by secreted Spitz was observed when the Rho and Star proteins were coexpressed with DER in S2 cells. In embryos mutant for rho or Star the ventralizing effect of secreted Spitz is epistatic, suggesting that Rho and Star may normally facilitate processing of the Spitz precursor. Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel. Schweitzer R R Shaharabany M M Seger R R Shilo B Z BZ eng Journal Article

UNITED STATES Genes Dev 8711660 0 Insect Hormones 0 Membrane Proteins 0 Phosphoproteins 0 Receptors, Invertebrate Peptide 0 Recombinant Fusion Proteins 0 Rho protein, Drosophila 0 drk protein, Drosophila 0 epidermal growth factor receptor homolog, Drosophila 0 rho-2 protein, Drosophila 0 steroidogenic acute regulatory protein 148175-53-5 spitz protein EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase IM Drk flb rho spi Animal Ca(2+)-Calmodulin Dependent Protein Kinase metabolism Cells, Cultured Drosophila melanogaster embryology genetics Ectoderm physiology Embryo, Nonmammalian metabolism ultrastructure Epistasis, Genetic Gene Expression Regulation, Developmental Insect Hormones metabolism Membrane Proteins genetics metabolism physiology secretion Phosphoproteins metabolism Phosphorylation Protein Processing, Post-Translational Receptor Protein-Tyrosine Kinases metabolism Receptor, Epidermal Growth Factor genetics physiology Receptors, Invertebrate Peptide genetics physiology Recombinant Fusion Proteins metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0144809 21676280 11819114 2002 01 30 2002 06 11 2003 01 03

0949-944X 211 12 2001 Dec Drosophila vitelline membrane cross-linking requires the fs(1)Nasrat, fs(1)polehole and chorion genes activities. 573-80 Abstract. During the final step of Drosophila vitelline membrane formation, the structural proteins composing this layer become cross-linked by covalent bonds. In the present report, we analyzed the vitelline membrane cross-linking in mutants having defects either in this layer or in the chorionic layers. In the fs(1)Nasrat and fs(1)polehole mutant alleles conferring defects in vitelline membrane formation, disruption of vitelline membrane cross-linking was observed, indicating the involvement of these two genes in the process. On the contrary, in the fs(1)Nasrat and fs(1)polehole alleles showing defects only at the termini of the embryo the vitelline membrane is properly formed, confirming a multifunctional activity of their gene products. Altered vitelline membrane cross-linking was also detected in a mutant of the chorion protein gene Cp36and in the chorion amplification mutant fs(1)K1214, suggesting a role of the structural components of chorion layers in the process of vitelline membrane hardening. Dipartimento di Biologia Evoluzionistica Sperimentale, Via Selmi 3, 40126 Bologna, Italy. Cernilogar F M FM Fabbri F F Andrenacci D D Taddei C C Gargiulo G G eng Journal Article 2001 12 01

Germany Dev Genes Evol 9613264 0 Drosophila Proteins 0 Egg Proteins 0 Membrane Proteins 0 Nasrat protein, Drosophila 0 Polehole protein, Drosophila 0 chorion proteins IM Animal Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics physiology Egg Proteins genetics metabolism Female Membrane Proteins genetics metabolism Mutation Ovary physiology ultrastructure Support, Non-U.S. Gov't Vitelline Membrane metabolism physiology FBrf0105830 98453412 9778512 1999 01 19 1999 01 19 2003 06 16

0950-1991 125 22 1998 Nov Homologous association of the Bithorax-Complex during embryogenesis: consequences for transvection in Drosophila melanogaster. 4541-52 Transvection is the phenomenon by which the expression of a gene can be controlled by its homologous counterpart in trans, presumably due to pairing of alleles in diploid interphase cells. Transvection or trans-sensing phenomena have been reported for several loci in Drosophila, the most thoroughly studied of which is the Bithorax-Complex (BX-C). It is not known how early trans-sensing occurs nor the extent or duration of the underlying physical interactions. We have investigated the physical proximity of homologous genes of the BX-C during Drosophila melanogaster embryogenesis by applying fluorescent in situ hybridization techniques together with high-resolution confocal light microscopy and digital image processing. The association of homologous alleles of the BX-C starts in nuclear division cycle 13, reaches a plateau of 70% in postgastrulating embryos, and is not perturbed by the transcriptional state of the genes throughout embryogenesis. Pairing frequencies never reach 100%, indicating that the homologous associations are in equilibrium with a dissociated state. We determined the effects of translocations and a zeste protein null mutation, both of which strongly diminish transvection phenotypes, on the extent of diploid homologue pairing. Although translocating one allele of the BX-C from the right arm of chromosome 3 to the left arm of chromosome 3 or to the X chromosome abolished trans-regulation of the Ultrabithorax gene, pairing of homologous alleles surprisingly was reduced only to 20-30%. A zeste protein null mutation neither delayed the onset of pairing nor led to unpairing of the homologous alleles. These data are discussed in the light of different models for trans-regulation. We examined the onset of pairing of the chromosome 4 as well as of loci near the centromere of chromosome 3 and near the telomere of 3R in order to test models for the mechanism of homologue pairing. Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, FRG. Gemkow M J MJ Verveer P J PJ Arndt-Jovin D J DJ eng Journal Article

ENGLAND Development 8701744 0 Abd-B proteins, Drosophila 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 zeste protein 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila IM Alleles Animal Chromosome Mapping Chromosome Painting Crosses, Genetic DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Gene Expression Regulation Gene Rearrangement Genes, Insect Homeodomain Proteins genetics In Situ Hybridization, Fluorescence Insect Proteins genetics Mitosis genetics Sequence Deletion Support, Non-U.S. Gov't Transcription, Genetic Translocation (Genetics) FBrf0052520 91265339 1982923 1991 07 22 1991 07 22 2001 11 02

0925-4773 33 1 1990 Dec Altering the regulatory targets of the Deformed protein in Drosophila embryos by substituting the Abdominal-B homeodomain. 83-93 The homeotic selector genes of Drosophila melanogaster encode transcriptional regulatory proteins that control the determination of different segmental fates. Binding of selector proteins to regulatory DNA sequences is mediated by an evolutionary conserved protein domain, the homeodomain. Although homeodomains encoded by the selector genes are very similar in their amino acid sequence and in vitro DNA-binding properties, here we provide additional evidence that the homeodomain is responsible for most of the regulatory specificity of the entire protein. A heat-shock promoter/selector gene was constructed that encodes a Deformed/Abdominal-B chimera in which the Abdominal-B homeodomain is substituted for that of Deformed. Expression of this chimeric protein throughout the embryo causes morphological transformation of anterior segments toward more posterior identities. A number of other homeotic selector genes, all normally repressed by Abdominal-B, are ectopically activated by the chimeric protein. These results support the hypothesis that the target specificity of similar homeodomain proteins is largely determined by the amino acid sequence of the homeodomain. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511. Kuziora M A MA McGinnis W W eng PO1-38913 PHS Journal Article

IRELAND Mech Dev 9101218 0 Heat-Shock Proteins 0 Recombinant Fusion Proteins 0 Transcription Factors IM Abd-A Abd-B Antp Dfd Scr Ubx abd-A abd-B hsp70 ry<up>505</up> Abdomen embryology Animal Animals, Genetically Modified Base Sequence Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Dominant Genes, Homeobox Genes, Synthetic Heat-Shock Proteins genetics Larva Molecular Sequence Data Morphogenesis genetics Recombinant Fusion Proteins biosynthesis genetics physiology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors genetics physiology Transcription, Genetic FBrf0051656 91006062 2120049 1990 11 21 1990 11 21 2000 12 18

0261-4189 9 11 1990 Nov Alternatively spliced transcripts of the sex-determining gene tra-2 of Drosophila encode functional proteins of different size. 3619-29 The Drosophila transformer-2 gene (tra-2) is required for female sex determination in somatic cells and for spermatogenesis in male germ cells. We studied the organization of the tra-2 gene and characterized the transcripts in wild type and mutant animals. Two transcripts are detected in males and females; they differ in their abundance and in the presence (minor transcript Tmin) or absence (major transcript Tmaj) of one exon. Two other transcripts are present only in male germ cells. One of these is rare (msTmin) and represents a spliced form of the other, more abundant transcript (msTmaj). The transcript Tmaj encodes a protein of 264 amino acids, whereas transcripts Tmin and msTmaj encode proteins that are truncated at the N-terminus. All three putative proteins contain a stretch of approximately 90 amino acids, the ribonucleoprotein motif (RNP motif), which shows similarity to a variety of different ribonucleoproteins. Transformation studies reveal that a cDNA corresponding to the transcript Tmaj can provide all the functions for female sex determination and male fertility. Surprisingly, a cDNA corresponding to the transcript msTmaj could only supply some female sex-determining function, but was unable to restore fertility in mutant males. Sequence analysis of two temperature-sensitive mutations provides evidence that the RNP motif represents an important functional domain of the tra-2 protein. Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138. Amrein H H Maniatis T T Nöthiger R R eng Journal Article

ENGLAND EMBO J 8208664 0 Oligonucleotides 0 RNA, Messenger 0 Ribonucleoproteins 0 transformer-2 protein IM Amino Acid Sequence Animal Base Sequence Drosophila melanogaster genetics Female Genes, Structural Male Molecular Sequence Data Mutation Oligonucleotides Polymerase Chain Reaction Polymorphism (Genetics) RNA Splicing RNA, Messenger genetics Restriction Mapping Ribonucleoproteins genetics Sex Determination (Analysis) Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0105857 99077280 9862464 1999 01 11 1999 01 11 2000 12 18

0014-5793 440 1-2 1998 Nov 27 The Drosophila inhibitor of apoptosis D-IAP1 suppresses cell death induced by the caspase drICE. 243-8 Many members of the Inhibitor of Apoptosis (IAP) family inhibit cell death and existing data suggest at least two mechanisms of action. Drosophila IAPs (D-IAP1 and D-IAP2) and a baculovirus-derived IAP, Op-IAP, physically interact with and inhibit the anti-apoptotic activity of Reaper, HID, and Grim, three genetically defined inducers of apoptosis in Drosophila, while human IAPs, c-IAP1, c-IAP2, and X-IAP interact with a number of different proteins including specific members of the caspase family of cysteine proteases which are crucial in the execution of cell death. We have examined whether insect-active IAPs can inhibit apoptosis induced by selected caspases, Drosophila drICE, Sf-caspase-1, and mammalian caspase-3, in insect SF-21 cells. D-IAP1 inhibited apoptosis induced by the active forms of all three caspases tested and physically interacted with the active, but not the proform of drICE. MIHA, the mouse homolog of X-IAP and an effective inhibitor of caspase-3, also interacted with and blocked apoptosis induced by active drICE but was relatively ineffective in blocking Sf-caspase-1. Op-IAP and D-IAP2 were unable to inhibit effectively any of the active caspases tested and failed to interact with drICE. The Drosophila IAPs and Op-IAP, but not MIHA, blocked HID-initiated activation of pro-drICE. We conclude that D-IAP1 is capable of inhibiting the activation of drICE as well as inhibiting apoptosis induced by the active form of drICE. In contrast, D-IAP2 and Op-IAP are more limited in their inhibitory targets and may be limited to inhibiting the activation of caspases. Department of Entomology, The University of Georgia, Athens 30602, USA. Kaiser W J WJ Vucic D D Miller L K LK eng AI38262 AI NIAID Journal Article

NETHERLANDS FEBS Lett 0155157 0 IAP-like protein, vertebrate 0 Insect Proteins 0 Neuropeptides 0 Protein Precursors 0 Proteins 0 Recombinant Fusion Proteins 0 Viral Proteins 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 inhibitor of apoptosis 2, Drosophila 0 inhibitor of apoptosis, nuclear polyhedrosis virus EC 3.4.22.- Caspases EC 3.4.22.- drICE protein IM Animal Apoptosis Baculoviridae Caspases genetics metabolism Cell Line Drosophila melanogaster Enzyme Activation Insect Proteins genetics metabolism Mice Models, Biological Neuropeptides genetics metabolism Protein Precursors metabolism Protein Processing, Post-Translational Proteins genetics metabolism Recombinant Fusion Proteins genetics metabolism Sequence Deletion Spodoptera Support, U.S. Gov't, P.H.S. Transfection Viral Proteins genetics metabolism FBrf0134503 21065970 11139276 2001 01 26 2001 06 21

1350-9047 7 11 2000 Nov The fly caspases. 1039-44 Caspases, a group of cysteine proteases, constitute the effector arm of the cell death machinery. There are seven caspases known in Drosophila, three of which contain long amino-terminal prodomains. Although, compared to mammalian caspases, much less is known about the biology of Drosophila caspases, many studies have shown that caspases are essential for programmed cell death in the fly and are likely to be regulated in ways similar to their mammalian counterparts. Studies on fly caspases have revealed some new insights on cell death regulation. For example, the transcript for the fly caspase DRONC is regulated by the hormone ecdysone during programmed cell death in specific tissues. Recent data on DRONC also suggest that some fly caspases may have unique substrate specificities not ascribed to mammalian caspases. The presence of multiple caspases in Drosophila indicates that apoptotic pathways in insects are likely to be as complex as in vertebrates. Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, PO Box 14, Rundle Mall, Adelaide, SA 5000, Australia. sharad.kumar@imvs.sa.gov.au Kumar S S Doumanis J J eng GENBANK AF240763 AF242735 AF275814 Journal Article Review Review, Tutorial

England Cell Death Differ 9437445 0 Protein Precursors 9007-43-6 Cytochrome c EC 3.4.22.- Caspases EC 3.4.22.- DRONC caspase IM Amino Acid Motifs Amino Acid Sequence Animal Apoptosis physiology Caspases chemistry genetics metabolism Cytochrome c metabolism Drosophila melanogaster enzymology growth & development physiology Molecular Sequence Data Phylogeny Protein Precursors Sequence Alignment Substrate Specificity Support, Non-U.S. Gov't 39 FBrf0151252 22157281 12167411 2002 08 08 2002 09 20

0012-1606 248 2 2002 Aug 15 gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila. 369-83 glial cells missing (gcm) is the primary regulator of glial cell fate in Drosophila. In addition, gcm has a role in the differentiation of the plasmatocyte/macrophage lineage of hemocytes. Since mutation of gcm causes only a decrease in plasmatocyte numbers without changing their ability to convert into macrophages, gcm cannot be the sole determinant of plasmatocyte/macrophage differentiation. We have characterized a gcm homolog, gcm2. gcm2 is expressed at low levels in glial cells and hemocyte precursors. We show that gcm2 has redundant functions with gcm and has a minor role promoting glial cell differentiation. More significant, like gcm, mutation of gcm2 leads to reduced plasmatocyte numbers. A deletion removing both genes has allowed us to clarify the role of these redundant genes in plasmatocyte development. Animals deficient for both gcm and gcm2 fail to express the macrophage receptor Croquemort. Plasmatocytes are reduced in number, but still express the early marker Peroxidasin. These Peroxidasin-expressing hemocytes fail to migrate to their normal locations and do not complete their conversion into macrophages. Our results suggest that both gcm and gcm2 are required together for the proliferation of plasmatocyte precursors, the expression of Croquemort protein, and the ability of plasmatocytes to convert into macrophages. Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. Alfonso Teresa B TB Jones Bradley W BW eng GENBANK AF461416 R01 NS 39373 NS NINDS Journal Article

United States Dev Biol 0372762 0 Drosophila Proteins 0 GCM protein 0 Gcm2 protein, Drosophila 0 Neuropeptides 0 Trans-Activators IM Amino Acid Sequence Animal Base Sequence Cell Differentiation Cell Division Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster cytology embryology metabolism Gene Expression Regulation, Developmental Human Macrophages cytology metabolism Molecular Sequence Data Mutation Neuroglia cytology metabolism Neuropeptides genetics metabolism Sequence Homology, Amino Acid Stem Cells cytology metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism FBrf0110661 99373334 10444068 1999 09 01 1999 09 01 2000 12 18

0021-9525 146 3 1999 Aug 9 Cytoplasmic dynein is required for the nuclear attachment and migration of centrosomes during mitosis in Drosophila. 597-608 Cytoplasmic dynein is a multisubunit minus-end-directed microtubule motor that serves multiple cellular functions. Genetic studies in Drosophila and mouse have demonstrated that dynein function is essential in metazoan organisms. However, whether the essential function of dynein reflects a mitotic requirement, and what specific mitotic tasks require dynein remains controversial. Drosophila is an excellent genetic system in which to analyze dynein function in mitosis, providing excellent cytology in embryonic and somatic cells. We have used previously characterized recessive lethal mutations in the dynein heavy chain gene, Dhc64C, to reveal the contributions of the dynein motor to mitotic centrosome behavior in the syncytial embryo. Embryos lacking wild-type cytoplasmic dynein heavy chain were analyzed by in vivo analysis of rhodamine-labeled microtubules, as well as by immunofluorescence in situ methods. Comparisons between wild-type and Dhc64C mutant embryos reveal that dynein function is required for the attachment and migration of centrosomes along the nuclear envelope during interphase/prophase, and to maintain the attachment of centrosomes to mitotic spindle poles. The disruption of these centrosome attachments in mutant embryos reveals a critical role for dynein function and centrosome positioning in the spatial organization of the syncytial cytoplasm of the developing embryo. University of Minnesota, Department of Genetics, Cell Biology and Development, St. Paul, Minnesota 55108-1095, USA. Robinson J T JT Wojcik E J EJ Sanders M A MA McGrail M M Hays T S TS eng Journal Article

UNITED STATES J Cell Biol 0375356 0 Insect Proteins EC 3.6.1.33 Dynein ATPase IM Animal Brain cytology embryology metabolism Cell Nucleus genetics metabolism Centrosome metabolism Cytoplasm metabolism Drosophila melanogaster cytology embryology genetics Dynein ATPase genetics metabolism Embryo, Nonmammalian cytology metabolism Female Giant Cells cytology metabolism Insect Proteins genetics metabolism Interphase Male Microtubules metabolism Mitosis Mitotic Spindle Apparatus metabolism Movement Mutation Nuclear Envelope metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0054048 92038996 1936994 1991 12 16 1991 12 16 2000 12 18

0890-9369 5 11 1991 Nov Regulation of doublesex pre-mRNA processing occurs by 3'-splice site activation. 2071-85 Sex-specific alternative processing of the doublesex (dsx) pre-mRNA controls somatic sexual differentiation in Drosophila melanogaster. Processing in the female-specific pattern results from the utilization of an upstream 3'-terminal exon and requires the activities of both the transformer (tra) and transformer-2 (tra-2) genes. Use of the more downstream male-specific terminal exons does not require the activities of these genes and is thus considered the default dsx-processing pattern. Here, we used transient expression of dsx pre-mRNAs in the presence or absence of tra and tra-2 gene products in Drosophila tissue culture cells to investigate the molecular mechanism controlling this alternative RNA-processing decision. These studies reveal that female-specific processing of dsx pre-mRNA is controlled by tra and tra-2 through the positive regulation of female-specific alternative 3'-terminal exon use. Delineation of cis-acting sequences necessary for regulation shows that a 540-nucleotide region from within the female exon is both necessary and sufficient for regulation. In addition, utilization of the female-specific 3'-splice site (3'SS) is regulated independently of female-specific polyadenylation. Regulated polyadenylation was obtained only in the presence of splicing, suggesting that activation of female-specific exon use occurs by 3'SS activation. Department of Biological Sciences, Stanford University, California 94305. Ryner L C LC Baker B S BS eng Journal Article

UNITED STATES Genes Dev 8711660 0 RNA Precursors 0 RNA-Binding Proteins 24937-83-5 Poly A EC 3.1.- Ribonucleases IM dsx tra tra-2 Animal Blotting, Northern Cells, Cultured Drosophila melanogaster genetics growth & development Exons genetics Female Gene Expression Regulation genetics Male Poly A genetics RNA Precursors genetics metabolism RNA Processing, Post-Transcriptional genetics RNA Splicing genetics RNA-Binding Proteins genetics Ribonucleases metabolism Sex Characteristics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection genetics FBrf0159242 22610382 12692559 2003 05 01 2003 06 18

1465-7392 5 5 2003 May Degradation of DIAP1 by the N-end rule pathway is essential for regulating apoptosis. 467-73 Some members of the inhibitor of apoptosis (IAP) protein family block apoptosis by binding to and neutralizing active caspases. We recently demonstrated that a physical association between IAP and caspases alone is insufficient to regulate caspases in vivo and that an additional level of control is provided by IAP-mediated ubiquitination of both itself and the associated caspases. Here we show that Drosophila IAP 1 (DIAP1) is degraded by the 'N-end rule' pathway and that this process is indispensable for regulating apoptosis. Caspase-mediated cleavage of DIAP1 at position 20 converts the more stable pro-N-degron of DIAP1 into the highly unstable, Asn-bearing, DIAP1 N-degron of the N-end rule degradation pathway. Thus, DIAP1 represents the first known metazoan substrate of the N-end rule pathway that is targeted for degradation through its amino-terminal Asn residue. We demonstrate that the N-end rule pathway is required for regulation of apoptosis induced by Reaper and Hid expression in the Drosophila melanogaster eye. Our data suggest that DIAP1 instability, mediated through caspase activity and subsequent exposure of the N-end rule pathway, is essential for suppression of apoptosis. We suggest that DIAP1 safeguards cell viability through the coordinated mutual destruction of itself and associated active caspases. The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK. Ditzel Mark M Wilson Rebecca R Tenev Tencho T Zachariou Anna A Paul Angela A Deas Emma E Meier Pascal P eng Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Neuropeptides 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 reaper peptide, Drosophila 7006-34-0 Asparagine EC 3.4.22.- Caspases IM Nat Cell Biol. 2003 May;5(5):373-6 12724766 Amino Acid Sequence physiology Animal Apoptosis genetics Asparagine metabolism Caspases metabolism Cell Survival physiology Cells, Cultured Drosophila Proteins deficiency genetics metabolism Drosophila melanogaster cytology metabolism Eye cytology metabolism Eye Abnormalities genetics metabolism Gene Deletion Mutation genetics Neuropeptides metabolism Phenotype Protein Structure, Tertiary physiology Signal Transduction genetics FBrf0102487 98263949 9601643 1998 08 12 1998 08 12 2003 06 16

0960-9822 8 10 1998 May 7 Evolution of the interaction between Hox genes and a downstream target. 587-90 Segmental identities along the insect body depend on the activities of Hox genes [1,2]. In Drosophila melanogaster, one well-studied Hox regulatory target is Distal-less (Dll), which is required for the development of distal limb structures [3]. In abdominal segments, Dll transcription is prevented when Hox proteins of the Bithorax Complex (BX-C) bind to cis-regulatory elements upstream of the Dll transcription start site [4,5]. Previous evolutionary comparisons of gene expression patterns suggest that this direct repression is conserved between Diptera and Lepidoptera, but is absent in the Crustacea [6,7]. We examined gene expression patterns in three orders of hexapods, all of which develop abdominal appendages, in order to determine when the strong repressive interaction between BX-C proteins and Dll appeared during evolution. In each of the species examined, Dll expression was initiated in abdominal cells despite the presence of high levels of BX-C proteins. It appears that the strong repressive effects of BX-C proteins on Dll expression arose relatively late in insect evolution. We suggest that the regulatory interaction between the BX-C genes and Dll has evolved within the hexapods in a complex, segment-specific manner. Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA. Palopoli M F MF Patel N H NH eng Journal Article

ENGLAND Curr Biol 9107782 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila IM Animal Coleoptera genetics DNA-Binding Proteins genetics Drosophila melanogaster genetics Evolution Gene Expression Genes, Homeobox Genes, Insect Homeodomain Proteins genetics Insect Proteins genetics Insects genetics Orthoptera genetics FBrf0092501 97178981 9053322 1997 03 13 1997 03 13 2001 11 02

0950-1991 124 2 1997 Jan Reciprocal localization of Nod and kinesin fusion proteins indicates microtubule polarity in the Drosophila oocyte, epithelium, neuron and muscle. 461-70 Polarization of the microtubule cytoskeleton is an early event in establishment of anterior-posterior polarity for the Drosophila oocyte. During stages 8-9 of oogenesis, when oskar mRNA is transported to the posterior pole of the oocyte, a fusion protein consisting of the plus-end-directed microtubule motor kinesin and beta-galactosidase (Kin:beta gal) similarly localizes to the posterior pole, thereby suggesting that plus ends of microtubules are pointed to the posterior. In this paper, we have substituted the motor domain of Kin:beta gal with the putative motor domain (head) from the kinesin-related protein Nod. In cells with defined microtubule polarity, the Nod:beta gal fusion protein is an in vivo minus-end reporter for microtubules. Nod:beta gal localizes to apical cytoplasm in epithelial cells and to the poles of mitotic spindles in dividing cells. In stage 8-10 oocytes, the Nod fusion localizes to the anterior margin, thus supporting the hypothesis that minus ends of microtubules at these stages are primarily at the anterior margin of the oocyte. The fusion protein also suggests a polarity to the microtubule cytoskeleton of dendrites and muscle fibers, as it accumulates at the ends of dendrites in the embryonic PNS and is excluded from terminal cytoplasm in embryonic muscle. Finally, the reciprocal in vivo localization of Nod:beta gal and Kin:beta gal suggests that the head of Nod may be a minus-end-directed motor. Department of Biochemistry and HHMI, University of California at San Francisco, 94143, USA. Clark I E IE Jan L Y LY Jan Y N YN eng Journal Article

ENGLAND Development 8701744 0 DNA Primers 0 Microtubule Proteins 0 Nod protein 0 Recombinant Fusion Proteins EC 3.2.1.23 beta-Galactosidase EC 3.6.1.- Kinesin IM Animal Animals, Genetically Modified Crosses, Genetic DNA Primers Dendrites physiology Drosophila melanogaster Embryo, Nonmammalian physiology Epithelial Cells Epithelium physiology Female Kinesin biosynthesis Male Microtubule Proteins biosynthesis Microtubules physiology ultrastructure Mitotic Spindle Apparatus Muscles cytology physiology Neurons cytology physiology Oocytes cytology physiology Oogenesis Polymerase Chain Reaction Recombinant Fusion Proteins biosynthesis Recombination, Genetic Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. beta-Galactosidase biosynthesis FBrf0048208 88284329 2840337 1988 09 06 1988 09 06 2000 12 18

0016-6731 119 2 1988 Jun Genetic interactions of modifier genes and modifiable alleles in Drosophila melanogaster. 391-7 We have examined the effects of mutations in the six allele-specific modifier genes su(Hw), e(we), su(f), su(s), su(wa), and su(pr) on the expression of 18 modifiable alleles, situated at 11 loci. Ten of the modifiable alleles are associated with insertions of the gypsy retrotransposon and the others include alleles associated with insertions of copia and 412. We tested or retested 90 of the 108 possible combinations and examined the expression of modifiable alleles in flies mutant for pairs of modifier genes in various heterozygous and homozygous configurations. Our principal findings are: (1) a screen of 40,000 mutagenized X chromosomes yielded three new mutations in known modifier genes, but revealed no new modifier genes; (2) the modification effects of different mutations in a given modifier gene were qualitatively similar; (3) each of the six modifiers suppressed some modifiable alleles, enhanced others, and had no noticeable effect on still others; (4) the modifier genes could be placed in four classes, according to their effects on the gypsy-insertion alleles; and (5) the effects of mutations in different modifier genes combined additively. Implications of these results for models of modifier gene action are discussed. Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138. Rutledge B J BJ Mortin M A MA Schwarz E E Thierry-Mieg D D Meselson M M eng Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements IM Alleles Animal Chromosome Mapping DNA Transposable Elements Drosophila melanogaster genetics Enhancer Elements (Genetics) Female Genes, Regulator Genotype Heterozygote Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Transcription, Genetic FBrf0054858 92051375 1834995 1991 12 17 1991 12 17 2000 12 18

0305-1048 19 21 1991 Nov 11 Polypeptide components of Drosophila small nuclear ribonucleoprotein particles. 5877-82 In eukaryotes splicing of pre-mRNAs is mediated by the spliceosome, a dynamic complex of small nuclear ribonucleoprotein particles (snRNPs) that associate transiently during spliceosome assembly and the splicing reaction. We have purified snRNPs from nuclear extracts of Drosophila cells by affinity chromatography with an antibody specific for the trimethylguanosine (m3G) cap structure of snRNAs U1-U5. The polypeptide components of Drosophila snRNPs have been characterized and shown to consist of a number of proteins shared by all the snRNPs, and some proteins which appear to be specific to individual snRNP particles. On the basis of their apparent molecular weight and antigenicity many of these common and particle specific Drosophila snRNP proteins are remarkably conserved between Drosophila and human spliceosomes. By probing western blots of the Drosophila snRNP polypeptides with a number of antisera raised against human snRNP proteins, Drosophila polypeptides equivalent to many of the HeLa snRNP-common proteins have been identified, as well as candidates for a number of U1, U2 and U5-specific proteins. Institute of Cell and Molecular Biology, University of Edinburgh. Paterson T T Beggs J D JD Finnegan D J DJ Lührmann R R eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 Antibodies, Monoclonal 0 Nucleoproteins 0 RNA Caps 0 Ribonucleoproteins 0 Ribonucleoproteins, Small Nuclear IM Animal Antibodies, Monoclonal Base Sequence Blotting, Western Centrifugation, Density Gradient Chromatography, Affinity Comparative Study Drosophila melanogaster chemistry Hela Cells chemistry Human Molecular Sequence Data Nucleoproteins analysis chemistry RNA Caps analysis isolation & purification Ribonucleoproteins chemistry isolation & purification Ribonucleoproteins, Small Nuclear Support, Non-U.S. Gov't FBrf0043808 87100165 3099787 1987 02 02 1987 02 02 2000 12 18

0006-291X 141 2 1986 Dec 15 Cloning of a Drosophila cDNA encoding a polypeptide similar to the human insulin receptor precursor. 474-81 A Drosophila cDNA clone was obtained using the human insulin receptor cDNA sequence as a probe. The 3586 bp nucleotide sequence predicted a single polypeptide of 1095 amino acid residues which showed considerable homology (35.2%) with the human insulin receptor precursor. Although the cDNA was incomplete at its 5'-terminal region, it encodes a transmembrane glycoprotein as a single precursor of a two subunit molecule having a structural architecture similar to that of the human insulin receptor precursor. The presumptive beta subunit carries a well conserved Tyr kinase domain which showed 63.5% homology with that of human insulin receptor; however the protein of the alpha subunit is only weakly conserved (25%). Nishida Y Y Hata M M Nishizuka Y Y Rutter W J WJ Ebina Y Y eng GENBANK M14778 Journal Article

UNITED STATES Biochem Biophys Res Commun 0372516 0 Glycoproteins 0 Protein Precursors 9007-49-2 DNA EC 2.7.1.112 Receptor, Insulin IM Amino Acid Sequence Animal Cloning, Molecular DNA genetics Drosophila melanogaster genetics Glycoproteins genetics Protein Conformation Protein Precursors genetics Receptor, Insulin genetics Solubility Support, Non-U.S. Gov't FBrf0105825 99054698 9832525 1999 03 04 1999 03 04 2003 06 16

0016-6731 150 4 1998 Dec Genetic characterization of the Drosophila melanogaster Suppressor of deltex gene: A regulator of notch signaling. 1477-85 The Notch receptor signaling pathway regulates cell differentiation during the development of multicellular organisms. A number of genes are known to be components of the pathway or regulators of the Notch signal. One candidate for a modifier of Notch function is the Drosophila Suppressor of deltex gene [Su(dx)]. We have isolated four new alleles of Su(dx) and mapped the gene between 22B4 and 22C2. Loss-of-function Su(dx) mutations were found to suppress phenotypes resulting from loss-of-function of Notch signaling and to enhance gain-of-function Notch mutations. Hairless, a mutation in a known negative regulator of the Notch pathway, was also enhanced by Su(dx). Phenotypes were identified for Su(dx) in wing vein development, and a role was demonstrated for the gene between 20 and 30 hr after puparium formation. This corresponds to the period when the Notch protein is involved in refining the vein competent territories. Taken together, our data indicate a role for Su(dx) as a negative regulator of Notch function. University of Manchester, School of Biological Sciences, Manchester M13 9PT, United Kingdom. Fostier M M Evans D A DA Artavanis-Tsakonas S S Baron M M eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Membrane Proteins 0 deltex protein, Drosophila 0 notch protein IM Alleles Animal Chromosome Mapping Drosophila melanogaster genetics Genes, Insect Genes, Suppressor genetics physiology Insect Proteins genetics physiology Membrane Proteins metabolism Signal Transduction Support, Non-U.S. Gov't Wing FBrf0037055 82124564 6799740 1982 04 12 1982 04 12 2000 12 18

0026-8925 183 1 1981 Characterisation of a new tumorous-head mutant of Drosophila melanogaster. 158-62 A new homoeotic mutant, I127, showing abnormal growths in the head region including homoeotic transformation of eye to genitalia and antenna to leg, was isolated in a screen designed to find new alleles of the tumourous head (tuh-3), mutation. Similarities in the phenotype and genetics of the mutant, and complementation studies with tuh-I; tuh-3, suggest that I127 is indeed an allele of tuh-3. In combination with the first chromosome modifier tuh-1, the mutant is temperature-sensitive during the third larval instar, giving an increased penetrance of the tumorous head phenotype when reared at 25 degrees C as opposed to 18 degrees C. The isolation of further alleles at the tumorous-head locus are essential. The type of morphological defects which can result from mutations at this locus would enable us to establish if this is a complex locus, and if null mutations are lethal during development. The interactions of the tumorous-head gene with first chromosome modifiers and other homoeotic mutations will only be understood if we are able to induce a number of mutations at this locus, and as a consequence begin to elucidate the role of the wild-type gene product in normal development. Bownes M M Roberts S S Dempster M M Bournias-Vardiabasis N N eng Journal Article

GERMANY, WEST Mol Gen Genet 0125036 IM Alleles Animal Drosophila melanogaster genetics Female Head abnormalities Male Mutation Phenotype Support, Non-U.S. Gov't Temperature FBrf0053393 92034992 1934069 1991 12 26 1991 12 26 2000 12 18

0092-8674 67 4 1991 Nov 15 The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. 717-22 Roughened is a dominant mutation of D. melanogaster that disrupts eye development. The majority of the ommatidia in the adult eye lack a single photoreceptor cell, which is most commonly the R7 cell. The Roughened mutation disrupts the early stages of photoreceptor cell determination. Roughened is a dominant gain-of-function mutation that results from a single amino acid change (Phe157 to Leu) in the Drosophila Rap1 protein. Loss of function Rap1 mutations are lethal. Drosophila Rap1 protein is 88% identical to human rap1A/K-rev1 protein, a putative antagonist of ras action. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720. Hariharan I K IK Carthew R W RW Rubin G M GM eng GENBANK M80535 M80539 S60911 S60914 S60917 S60919 S60920 S60969 S61522 S61524 Journal Article

UNITED STATES Cell 0413066 EC 3.6.1.- GTP-Binding Proteins EC 3.6.1.- rap GTP-Binding Proteins IM R Rap1 Amino Acid Sequence Animal Comparative Study Drosophila melanogaster embryology genetics Eye embryology GTP-Binding Proteins physiology Genes, Dominant Molecular Sequence Data Mutation Sequence Alignment Support, Non-U.S. Gov't rap GTP-Binding Proteins FBrf0090681 97044458 8889529 1997 02 11 1997 02 11 2000 12 18

0016-6731 144 2 1996 Oct Polygenic mutation in Drosophila melanogaster: genetic interactions between selection lines and candidate quantitative trait loci. 671-88 We have investigated genetic interactions between spontaneous mutations affecting abdominal and sternopleural bristle number that have accumulated in 12 long-term selection lines derived from an inbred strain, and mutations at 14 candidate bristle number quantitative trait loci. The quantitative test for complementation was to cross the selection lines to an inbred wild-type strain (the control cross) and to a derivative of the control strain into which the mutant allele at the candidate locus to be tested was substituted (the tester strain). Genetic interactions between spontaneous mutations affecting bristle number and the candidate locus mutations were common, and in several cases the interaction effects were different in males and females. Analyses of variance of the (tester- control) differences among and within groups of replicate lines selected in the same direction for the same trait showed significant group effects for several candidate loci. Genetically, the interactions could be caused by allelism of, and/ or epistasis between, spontaneous mutations in the selection lines and the candidate locus mutations. It is possible that much of the response to selection was from new mutations at candidate bristle number quantitative trait loci, and that for some of these loci, mutation rates were high. Department of Genetics, North Carolina State University, Raleigh 27695, USA. trudy_mackay@ncsu.edu Mackay T F TF Fry J D JD eng GM-45146 GM NIGMS GM-45344 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Analysis of Variance Animal Chromosome Mapping Drosophila melanogaster genetics Female Genes, Insect Genetic Complementation Test Male Mutation Phylogeny Selection (Genetics) Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0057331 92350278 1641021 1992 09 01 1992 09 01 2001 11 26

0028-0836 358 6385 1992 Jul 30 Induction of germ cell formation by oskar. 387-92 The oskar gene directs germ plasm assembly and controls the number of germ cell precursors formed at the posterior pole of the Drosophila embryo. Mislocalization of oskar RNA to the anterior pole leads to induction of germ cells at the anterior. Of the eight genes necessary for germ cell formation at the posterior, only three, oskar, vasa and tudor, are essential at an ectopic site. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142. Ephrussi A A Lehmann R R eng Journal Article

ENGLAND Nature 0410462 0 RNA, Messenger IM Nature. 1992 Jul 30;358(6385):368-9 1641016 capu mago osk spir stau tud vas vls Abdomen embryology Animal Drosophila melanogaster embryology Embryonic Induction Gene Expression Genes, Structural Germ Cells Morphogenesis RNA, Messenger metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0093093 97247733 9093856 1997 10 06 1997 10 06 2003 06 16

0016-6731 145 4 1997 Apr oroshigane, a new segment polarity gene of Drosophila melanogaster, functions in hedgehog signal transduction. 1041-52 Here we describe a new segment polarity gene of Drosophila melanogaster, oroshigane (oro). Identified as a dominant enhancer of Bar (B), oro is also recessive embryonic lethal, and homozygous oro embryos show variable substitution of naked cuticle with denticles. These patterns are distinctly similar to those of hedgehog (hh) and wingless (wg) embryos, which indicates that oro functions in determining embryonic segment polarity. Evidence that oro function is involved in Hh signal transduction during embryogenesis is provided by its genetic interactions with the segment polarity genes patched (ptc) and fused (fu). Furthermore, ptcIN is a dominant suppressor of the oro embryonic lethal phenotype, suggesting a close and dose-dependent relationship between oro and ptc in Hh signal transduction. oro function is also required in imaginal development. The oroI allele significantly reduces decapentaplegic (dpp), but not hh, expression in the eye imaginal disc. Furthermore, oro enhances the fui wing phenotype in a dominant manner. Based upon the interactions of oro with hh, ptc, and fu, we propose that the oro gene plays important roles in Hh signal transduction. Molecular and Cell Biology Graduate Program, University of Maryland, College Park 20742, USA. tanda@zool.umd.edu Epps J L JL Jones J B JB Tanda S S eng Journal Article

UNITED STATES Genetics 0374636 0 Eye Proteins 0 Insect Proteins 0 Membrane Proteins 0 dpp protein, Drosophila 0 patched protein, Drosophila 142298-55-3 BarH1 protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian growth & development ultrastructure Epistasis, Genetic Eye embryology ultrastructure Eye Proteins biosynthesis genetics Female Gene Expression Regulation, Developmental Genes, Lethal Genes, Regulator Genes, Structural, Insect Genes, Suppressor Insect Proteins genetics physiology Male Membrane Proteins physiology Morphogenesis Phenotype Protein-Serine-Threonine Kinases physiology Signal Transduction physiology Support, Non-U.S. Gov't Wing embryology ultrastructure FBrf0058506 93246263 8482549 1993 05 28 1993 05 28 2000 12 18

0378-1119 126 2 1993 Apr 30 The alternative 5'-end of the Drosophila melanogaster epidermal growth factor receptor cDNA (DER) is part of the D14-3-3 cDNA. 293-4 A portion of the cDNA reported as a novel cDNA encoding the Drosophila melanogaster homolog of the bovine 14-3-3 protein by Swanson and Ganguly [Gene 113 (1992) 183-190] already exists in the database. It was originally reported as an alternative 5' end of the D. melanogaster homolog of the epidermal growth factor receptor (DER). Schejter and Shilo [Cell 56 (1989) 1093-1164] later reported that this finding was due to a cloning artifact that joined the 14-3-3 cDNA onto the DER cDNA. McConnell J E JE Hodges P E PE eng GENBANK K03418 M77518 Letter

NETHERLANDS Gene 7706761 0 14-3-3 protein 0 Nerve Tissue Proteins 9007-49-2 DNA EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Base Sequence Cattle DNA Drosophila melanogaster Molecular Sequence Data Nerve Tissue Proteins genetics Receptor, Epidermal Growth Factor genetics Sequence Homology, Nucleic Acid FBrf0080007 95229054 7713425 1995 05 18 1995 05 18 2001 03 23

0016-6731 139 2 1995 Feb R1 and R2 retrotransposable elements of Drosophila evolve at rates similar to those of nuclear genes. 685-95 The non-long-terminal repeat retrotransposable elements, R1 and R2, insert at unique locations in the 28S ribosomal RNA genes of insects. Based on the nucleotide sequences of these elements in the eight members of the melanogaster species subgroup of the genus Drosophila, they have been maintained by vertical germline transmission for the 17-20 million year history of this subgroup. The stable inheritance of R1 and R2 within these species has enabled a determination of their nucleotide substitution rates. The sequence of the R1 and R2 elements from D. ambigua, a member of the obscura species group, has also been determined to enable an extrapolation of this rate over an estimated 45-60 million years. The mean rate of substitutions at synonymous sites (Ks) was 6.6 and 9.6 times the rate at replacement sites (Ka) in the R1 and R2 elements, respectively. Both elements appear to have been under selective pressure to maintain their open reading frames and thus their ability to retrotranspose for most of their evolution in these lineages. Using the rate of change at synonymous sites (Ks) as the best indicator of the nucleotide substitution rate, the mean Ks values for R1 and R2 were 2.3 and 2.2 times that of the alcohol dehydrogenase (Adh) genes. However, this faster rate is a result of the lower codon usage bias of R1 and R2 compared with that of Adh. When the Ks rates of R1 and R2 were compared with that of a larger number of nuclear genes available from at least two of the nine species under investigation, R1 and R2 were found to evolve in most lineages at rates similar to that of nuclear genes with low codon bias. The ability of R1 and R2 to maintain their presence in this species subgroup by retrotransposition while exhibiting rates of nucleotide evolution similar to nuclear genes suggests these transposition events are rare or not as error prone as that of retroviruses. Department of Biology, University of Rochester, New York 14627, USA. Eickbush D G DG Lathe W C WC 3rd Francino M P MP Eickbush T H TH eng GENBANK J01066 J04167 L10670 L14417 L14421 L14426 M17478 M21227 M33977 M36581 M60982 M84581 X02497 X03810 X03812 X04672 X05179 X05723 X06285 X06286 X14233 X53423 X54116 X54118 X54120 X66930 X75541 Y00308 Z00032 Z00033 Journal Article

UNITED STATES Genetics 0374636 0 Codon 0 Retroelements IM Amino Acid Sequence Animal Base Sequence Codon genetics Drosophila genetics Drosophila melanogaster genetics Evolution Genes, Insect Molecular Sequence Data Phylogeny Retroelements Sequence Analysis, DNA Support, U.S. Gov't, Non-P.H.S. Variation (Genetics) genetics FBrf0155711 22354109 12466201 2002 12 05 2003 03 10

0950-1991 130 2 2003 Jan The Drosophila trithorax group gene tonalli (tna) interacts genetically with the Brahma remodeling complex and encodes an SP-RING finger protein. 343-54 The trithorax group genes are required for positive regulation of homeotic gene function. The trithorax group gene brahma encodes a SWI2/SNF2 family ATPase that is a catalytic subunit of the Brm chromatin-remodeling complex. We identified the tonalli (tna) gene in Drosophila by genetic interactions with brahma. tna mutations suppress Polycomb phenotypes and tna is required for the proper expressions of the Antennapedia, Ultrabithorax and Sex combs reduced homeotic genes. The tna gene encodes at least two proteins, a large isoform (TnaA) and a short isoform (TnaB). The TnaA protein has an SP-RING Zn finger, conserved in proteins from organisms ranging from yeast to human and thought to be involved in the sumoylation of protein substrates. Besides the SP-RING finger, the TnaA protein also has extended homology with other eukaryotic proteins, including human proteins. We show that tna mutations also interact with mutations in additional subunits of the Brm complex, with mutations in subunits of the Mediator complex, and with mutations of the SWI2/SNF2 family ATPase gene kismet. We propose that Tna is involved in postranslational modification of transcription complexes. Departamento de Fisiología Molecular y Genética del Desarrollo, Instituto de Biotecnología, UNAM, Cuernavaca, Morelos 62250, México. Gutiérrez Luis L Zurita Mario M Kennison James A JA Vázquez Martha M eng Journal Article

England Development 8701744 0 Carrier Proteins 0 Cell Cycle Proteins 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Homeodomain Proteins 0 Protein Isoforms 0 Trans-Activators 0 brahma protein 0 tonalli protein, Drosophila 0 trithorax gene product IM Amino Acid Sequence Animal Carrier Proteins chemistry genetics metabolism Cell Cycle Proteins metabolism DNA-Binding Proteins genetics metabolism Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster genetics physiology Female Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Homeodomain Proteins genetics metabolism Human Molecular Sequence Data Multigene Family Mutation Phenotype Protein Isoforms genetics metabolism Sequence Alignment Support, Non-U.S. Gov't Trans-Activators metabolism Zinc Fingers FBrf0041539 85012651 6434989 1984 11 14 1984 11 14 2000 12 18

0028-0836 311 5983 1984 Sep 20-26 Information for the dorsal--ventral pattern of the Drosophila embryo is stored as maternal mRNA. 223-7 Maternal-effect mutations in 10 loci in Drosophila produce totally 'dorsalized' embryos. Injection of RNA isolated from wild-type embryos into mutants at six loci partially restores dorsal-ventral polarity. For the mutant snake, injection of poly(A)+ RNA restores a complete dorsal-ventral pattern. Anderson K V KV Nüsslein-Volhard C C eng Journal Article

ENGLAND Nature 0410462 0 RNA, Messenger IM Animal Drosophila melanogaster embryology genetics Morphogenesis Phenotype RNA, Messenger genetics Support, Non-U.S. Gov't FBrf0134786 20500226 11048731 2000 10 25 2000 11 07

0028-0836 407 6805 2000 Oct 12 Apoptosis in development. 796-801 Essential to the construction, maintenance and repair of tissues is the ability to induce suicide of supernumerary, misplaced or damaged cells with high specificity and efficiency. Study of three principal organisms--the nematode, fruitfly and mouse--indicate that cell suicide is implemented through the activation of an evolutionarily conserved molecular programme intrinsic to all metazoan cells. Dysfunctions in the regulation or execution of cell suicide are implicated in a wide range of developmental abnormalities and diseases. Signal Transduction Laboratory, Imperial Cancer Research Fund, London, UK. meierp@icr.ac.uk Meier P P Finch A A Evan G G eng Journal Article Review Review, Tutorial

ENGLAND Nature 0410462 IM Animal Apoptosis Caenorhabditis elegans Drosophila melanogaster Growth physiology Human Mice Morphogenesis physiology 75 FBrf0053811 92146282 1782877 1992 03 16 1992 03 16 2000 12 18

0950-1991 113 2 1991 Oct The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal. 715-22 The gene scute (sc) has a dual function: the scute function which is involved in neurogenesis and the sisterless-b function which is involved in generating the X:A signal that determines the state of activity of Sxl, a gene that controls sex determination and dosage compensation. We show here that the lethal phase of sc- females is embryonic and caused by the lack of Sxl function. We also analyze the time in development when sc and Sxl interact by means of (a) determining the thermosensitive phase (TSP) of the interaction between Sxl and sc and (b) a chimeric gene in which sc is under the control of a heat-shock promoter (HSSC-3). Pulses of sc expression from the HSSC-3 activate Sxl only at a very specific and early stage in development, which coincides with the TSP of the interaction between sc and Sxl. It corresponds to the syncytial blastoderm stage and coincides with the time when the X:A signal regulates Sxl. At this stage sc undergoes a homogeneous transient expression in wild-type flies. We conclude that the sc expression at the syncytial blastoderm is responsible for its sisterless-b function. Since sc expression from the HSSC-3 fully suppresses the sisterless-b phenotype, we further conclude that the sisterless-b function is exclusively provided by the sc protein. Finally, we have analyzed, by in situ hybridization, the effect of sc and sis-a mutations on the embryonic transcription of Sxl. Our results support the view that the control of Sxl by the X:A signal occurs at the transcriptional level. Centre de Investigaciones Biológicas, Madrid, Spain. Torres M M Sánchez L L eng Journal Article

ENGLAND Development 8701744 IM Animal Blastoderm physiology Drosophila melanogaster anatomy & histology genetics Genes, Lethal physiology Genes, Structural physiology Genitalia anatomy & histology Heat Molecular Probe Techniques Sex Determination (Analysis) Support, Non-U.S. Gov't FBrf0139619 21538564 11682305 2001 10 29 2002 01 11

0959-437X 11 6 2001 Dec Genome-wide variation in the human and fruitfly: a comparison. 627-34 Average levels of nucleotide diversity are ten-fold lower in humans than in the fruitfly, Drosophila melanogaster. Despite this difference, apparently as a result of a lower population size, patterns of genomic diversity are strikingly similar in being correlated with local rates of recombination, and influenced by similar interactions between positive natural selection and recombination. Both species also show lower levels of variation on average in non-African compared to African populations, reflecting a similar evolutionary history and perhaps both natural selection and founder effects in new environments. Department of Molecular Biology and Genetics, Biotechnology Building, Cornell University, Ithaca, New York 14853, USA. cfa1@cornell.edu Aquadro C F CF Bauer DuMont V V Reed F A FA eng Journal Article Review Review, Tutorial

England Curr Opin Genet Dev 9111375 IM Alleles Animal Chromosomes genetics Comparative Study Crosses, Genetic Drosophila melanogaster genetics physiology Evolution Gene Conversion Genetics, Population Genome Human Linkage Disequilibrium Mutation Recombination, Genetic Selection (Genetics) Support, U.S. Gov't, P.H.S. Variation (Genetics) 88 FBrf0160790 22623392 12737810 2003 05 09 2003 06 16

1534-5807 4 5 2003 May The hexapeptide and linker regions of the AbdA Hox protein regulate its activating and repressive functions. 761-8 The Hox family transcription factors control diversified morphogenesis during development and evolution. They function in concert with Pbc cofactor proteins. Pbc proteins bind the Hox hexapeptide (HX) motif and are thereby thought to confer DNA binding specificity. Here we report that mutation of the AbdA HX motif does not alter its binding site selection but does modify its transregulatory properties in a gene-specific manner in vivo. We also show that a short, evolutionarily conserved motif, PFER, in the homeodomain-HX linker region acts together with the HX to control an AbdA activation/repression switch. Our in vivo data thus reveal functions not previously anticipated from in vitro analyses for the hexapeptide motif in the regulation of Hox activity. Laboratoire de Génétique et Physiologie du Développement, IBDM, CNRS, Université de la méditerranée, Parc Scientifique de Luminy, Case 907, 13288 Marseille Cedex 09, France. Merabet Samir S Kambris Zakaria Z Capovilla Maria M Bérenger Hélène H Pradel Jacques J Graba Yacine Y eng Journal Article

United States Dev Cell 101120028 0 Drosophila Proteins 0 Homeodomain Proteins 0 Hox protein Abdominal-A, Drosophila 0 Nerve Tissue Proteins 0 Transcription Factors 0 exd protein, Drosophila 0 homothorax protein IM Amino Acid Motifs Amino Acid Sequence Animal Conserved Sequence DNA Footprinting Drosophila Proteins chemistry metabolism Drosophila melanogaster embryology genetics metabolism Electrophoretic Mobility Shift Assay Gene Expression Regulation, Developmental Homeodomain Proteins chemistry metabolism In Situ Hybridization Mesoderm metabolism Molecular Sequence Data Nerve Tissue Proteins chemistry metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't Transcription Factors metabolism FBrf0144770 21849952 11862451 2002 02 25 2002 05 01 2003 01 03

0009-5915 110 7 2001 Dec The actin loci in the genus Drosophila: establishment of chromosomal homologies among five palearctic species of the Drosophila obscura group by in situ hybridization. 441-50 Chromosomal homologies among the four palearctic Drosophila obscura group species D. ambigua, D. tristis, D. obscura, and D. subsilvestris and the "trans-palearctic" species D. bifasciata were established by in situ hybridization using the 5C actin gene of D. melanogaster as a probe. In all species two labeling sites were detected in each of chromosomal elements C and E and one in each of chromosomal elements A and D. In addition one labeling site was detected on element B for the species D. subsilvestris and D. bifasciata. The conservative distribution pattern of the genes of the actin multigene family, the similarities of the locations of the actin genes in the chromosomes of the five species studied, together with the concordant evidence of synteny of visible and other genetic markers as well as the similarities in banding patterns, all agree with the conclusion that the chromosomal elements have retained their essential identity throughout the evolution of these species. Using in situ hybridization detailed information of some homologous regions of chromosomes can also be established. Department of Genetics, Faculty of Biotechnology, Agricultural University of Athens, Athens, Greece. gbotinas@aua.gr Bondinas G P GP Loukas M G MG Goulielmos G N GN Sperlich D D eng Journal Article 2001 10 30

Germany Chromosoma 2985138R 0 Actins IM Actins genetics Alleles Animal Centromere genetics Chromosome Banding Chromosome Mapping Chromosomes ultrastructure Comparative Study Drosophila genetics ultrastructure Evolution, Molecular In Situ Hybridization methods Inversion (Genetics) Phylogeny Salivary Glands ultrastructure Sequence Homology, Nucleic Acid Species Specificity Telomere genetics FBrf0104776 98359954 9693146 1998 10 14 1998 10 14 2002 11 01

0950-1991 125 17 1998 Sep Patterned epidermal cell death in wild-type and segment polarity mutant Drosophila embryos. 3427-36 Programmed cell death plays an essential role in the normal embryonic development of Drosophila melanogaster. One region of the embryo where cell death occurs, but has not been studied in detail, is the abdominal epidermis. Because cell death is a fleeting process, we have used time-lapse, fluorescence microscopy to map epidermal apoptosis throughout embryonic development. Cell death occurs in a stereotypically striped pattern near both sides of the segment border and to a lesser extent in the middle of the segment. This map of wild-type cell death was used to determine how cell death patterns change in response to genetic perturbations that affect epidermal patterning. Previous studies have suggested that segment polarity mutant phenotypes are partially the result of increased cell death. Mutations in wingless, armadillo, and gooseberry led to dramatic increases in apoptosis in the anterior of the segment while a naked mutation resulted in a dramatic increase in the death of engrailed cells in the posterior of the segment. These results show that segment polarity gene expression is necessary for the survival of specific rows of epidermal cells and may provide insight into the establishment of the wild-type epidermal cell death pattern. Department of Biological Sciences and the Center for Light Microscope Imaging and Biotechnology and Department of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Pazdera T M TM Janardhan P P Minden J S JS eng HD31642 HD NICHD Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Proto-Oncogene Proteins 0 armadillo protein, Drosophila 117758-26-6 wingless protein, Drosophila IM Animal Apoptosis genetics Body Patterning genetics Drosophila melanogaster cytology embryology genetics Epidermis cytology embryology Genes, Insect Homozygote In Situ Hybridization Insect Proteins genetics Microscopy, Fluorescence Mutation Proto-Oncogene Proteins genetics Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Temperature FBrf0068513 94163982 8119134 1994 04 04 1994 04 04 2000 12 18

0950-1991 120 1 1994 Jan Functions of the cytoplasmic domain of the beta PS integrin subunit during Drosophila development. 91-102 Integrins constitute a family of membrane-spanning, heterodimeric proteins that mediate adhesive interactions between cells and surrounding extracellular matrices (or other cells) and participate in signal transduction. We are interested in assessing integrin functions in the context of developing Drosophila melanogaster. This report, using mutants of the beta PS subunit encoded by the myospheroid (mys) locus, analyzes the relationships between integrin protein structure and developmental functions in an intact organism. As a first step in this analysis, we demonstrated the ability of a fragment of wild-type mys genomic DNA, introduced into the germ line in a P-element vector P[mys+], to rescue phenotypes attributed to lack of (or defects in) the endogenous beta PS during several discrete morphogenetic events. We then produced in vitro a series of modifications of the wild-type P[mys+] transposon, which encode beta PS derivatives with mutations within the small and highly conserved cytoplasmic domain. In vivo analysis of these mutant transposons led to the following conclusions. (1) The cytoplasmic tail of beta PS is essential for all developmental functions of the protein that were assayed. (2) An intron at a conserved position in the DNA sequence encoding the cytoplasmic tail is thought to participate in important alternative splicing events in vertebrate beta integrin subunit genes, but is not required for the developmental functions of the mys gene assayed here. (3) Phosphorylation on two conserved tyrosines found in the C terminus of the beta PS cytoplasmic tail is not necessary for the tested developmental functions. (4) Four highly conserved amino acid residues found in the N-terminal portion of the cytoplasmic tail are important but not critical for the developmental functions of beta PS; furthermore, the efficiencies with which these mutant proteins function during different morphogenetic processes vary greatly, strongly suggesting that the cytoplasmic interactions involving PS integrins are developmentally modulated. Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138. Grinblat Y Y Zusman S S Yee G G Hynes R O RO Kafatos F C FC eng Journal Article

ENGLAND Development 8701744 0 Integrins 0 integrin PS, Drosophila IM Amino Acid Sequence Animal Cell Adhesion genetics Cytoplasm physiology Drosophila melanogaster anatomy & histology embryology genetics Genetic Techniques Integrins genetics physiology Molecular Sequence Data Morphogenesis genetics Mutation genetics Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0075082 95073590 7982557 1994 12 30 1994 12 30 2000 12 18

0016-6731 137 4 1994 Aug Molecular genetic analysis of the Drosophila melanogaster gene absent, small or homeotic discs1 (ash1). 1027-38 The absent, small or homeotic discs1 gene (ash1) is one of the trithorax set of genes. Recessive loss of function mutations in ash1 cause homeotic transformations of imaginal disc derived tissue which resemble phenotypes caused by partial loss or gain of function mutations in genes of the Antennapedia Complex and bithorax Complex. F2 screens were used to isolate P element insertion alleles and EMS-induced alleles of ash1, including one temperature-sensitive allele, and an F1 screen was used to isolate gamma-ray-induced alleles. Analysis of ash1 mutant flies that survive until the adult stage indicates that not only imaginal disc- and histoblast-derived tissues are affected but also that oogenesis requires ash1 function. Mutations in the gene brahma (brm) which also is one of the trithorax set of genes interact with mutations in ash1 such that non-lethal ash1 +/+ brm double heterozygotes have a high penetrance of homeotic transformations in specific imaginal disc- and histoblast-derived tissues. The cytogenetic location of ash1 was determined to be 76B6-11 by the breakpoint of a translocation recovered in the F1 screen. The gene Shal, which is located cytogenetically nearby ash1, was used to initiate an 84-kb genomic walk within which the ash1 gene was identified. The ash1 gene encodes a 7.5-kb transcript that is expressed throughout development but is present at higher levels during the embryonic and pupal stages than during the larval stages. During the larval stages the transcript accumulates primarily in imaginal discs. During oogenesis the transcript accumulates in the nurse cells of developing egg chambers. Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218. Tripoulas N A NA Hersperger E E La Jeunesse D D Shearn A A eng AG01822 AG NIA Journal Article

UNITED STATES Genetics 0374636 0 DNA, Complementary 0 Trans-Activators 0 brahma protein IM ash1 brm Alleles Animal Chromosome Mapping Chromosome Walking DNA, Complementary genetics Drosophila melanogaster embryology genetics Female Gene Expression Genes, Homeobox Genes, Lethal Genes, Structural, Insect Heat In Situ Hybridization Male Morphogenesis genetics Mutagenesis Oogenesis genetics Phenotype Support, U.S. Gov't, P.H.S. Trans-Activators genetics FBrf0079938 95309679 7789766 1995 07 21 1995 07 21 2000 12 18

0016-6731 139 4 1995 Apr A genetic analysis of intersex, a gene regulating sexual differentiation in Drosophila melanogaster females. 1649-61 Sex-type in Drosophila melanogaster is controlled by a hierarchically acting set of regulatory genes. At the terminus of this hierarchy lie those regulatory genes responsible for implementing sexual differentiation: genes that control the activity of target loci whose products give rise to sexually dimorphic phenotypes. The genetic analysis of the intersex (ix) gene presented here demonstrates that ix is such a terminally positioned regulatory locus. The ix locus has been localized to the cytogenetic interval between 47E3-6 and 47F11-18. A comparison of the morphological and behavioral phenotypes of homozygotes and hemizygotes for three point mutations at ix indicates that the null phenotype of ix is to transform diplo-X animals into intersexes while leaving haplo-X animals unaffected. Analysis of X-ray induced, mitotic recombination clones lacking ix+ function in the abdomen of diplo-X individuals indicates that the ix+ product functions in a cell-autonomous manner and that it is required at least until the termination of cell division in this tissue. Taken together with previous analyses, our results indicate that the ix+ product is required to function with the female-specific product of doublesex to implement appropriate female sexual differentiation in diplo-X animals. Department of Biological Sciences, Stanford University, California 94305, USA. Chase B A BA Baker B S BS eng Journal Article

UNITED STATES Genetics 0374636 IM ix Alleles Animal Chromosome Mapping Drosophila melanogaster genetics physiology Female Haplotypes Homozygote Phenotype Point Mutation Sex Behavior, Animal Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0097693 97370004 9226445 1997 08 25 1997 08 25 2003 06 16

0950-1991 124 14 1997 Jul DPP controls tracheal cell migration along the dorsoventral body axis of the Drosophila embryo. 2741-50 We report that DPP signaling is required for directed tracheal cell migration during Drosophila embryogenesis. The failure of tracheal cells to receive the DPP signal from adjacent dorsal and ventral cells results in the absence of dorsal and ventral migrations. Ectopic DPP signaling can reprogram cells in the center of the placode to adopt a dorsoventral migration behavior. The effects observed in response to ectopic DPP signaling are also observed upon the tracheal-specific expression of a constitutive active DPP type I receptor (TKV(Q253D)), indicating that the DPP signal is received and transmitted in tracheal cells to control their migration behavior. DPP signaling determines localized gene expression patterns in the developing tracheal placode, and is also required for the dorsal expression of the recently identified BRANCHLESS (BNL) guidance molecule, the ligand of the BREATHLESS (BTL) receptor. Thus, DPP plays a dual role during tracheal cell migration. It is required to control the dorsal expression of the BNL ligand; in addition, the DPP signal recruits groups of dorsal and ventral tracheal cells and programs them to migrate in dorsal and ventral directions. Abteilung Zellbiologie, Biozentrum, Universität Basel, Switzerland. Vincent S S Ruberte E E Grieder N C NC Chen C K CK Haerry T T Schuh R R Affolter M M eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Growth Substances 0 Homeodomain Proteins 0 Insect Proteins 0 KNI protein 0 Receptors, Cell Surface 0 Receptors, Growth Factor 0 Repressor Proteins 0 Transcription Factors 0 branchless protein, Drosophila 0 dpp protein, Drosophila 0 sal protein EC 2.7.1.- DTFR protein, Drosophila EC 2.7.1.37 Activin Receptors EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Activin Receptors Animal Cell Movement DNA-Binding Proteins physiology Drosophila melanogaster embryology Embryonic Induction Gene Expression Regulation, Developmental Growth Substances physiology Homeodomain Proteins physiology Insect Proteins physiology Morphogenesis Protein-Serine-Threonine Kinases physiology Receptors, Cell Surface physiology Receptors, Growth Factor physiology Repressor Proteins physiology Signal Transduction Support, Non-U.S. Gov't Trachea embryology Transcription Factors physiology Transcription, Genetic FBrf0047945 89030619 2903050 1988 12 22 1988 12 22 2000 12 18

0261-4189 7 10 1988 Oct Different transcripts of the Drosophila Abd-B gene correlate with distinct genetic sub-functions. 3233-44 Abdominal-B (Abd-B) is a homeotic selector gene required for the correct development of abdominal segments 5-9. This gene contains at least two different genetic sub-functions which act as 'morphogenetic' or 'regulatory' elements within a single lethal complementation group. In an effort to identify the molecular nature of these sub-functions we have characterized homeobox-containing transcripts of Abd-B. The Abd-B transcripts can be grouped into four major classes whose diversity arises through differential exon splicing. We have isolated cDNAs which represent three of the transcript classes, designated alpha, beta and gamma. Their expression patterns, coupled with previous molecular genetic analyses of Abd-B, suggest that the alpha transcript class encodes the 'morphogenetic' sub-function while the beta transcript class contributes to the 'regulatory' sub-function. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511. Kuziora M A MA McGinnis W W eng Journal Article

ENGLAND EMBO J 8208664 0 RNA, Messenger IM Animal Cloning, Molecular Drosophila melanogaster embryology genetics Exons Gene Expression Regulation Genes, Homeobox Mutation Nucleic Acid Hybridization RNA Splicing RNA, Messenger genetics Restriction Mapping Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Tissue Distribution Transcription, Genetic FBrf0091063 97156902 9003283 1997 02 12 1997 02 12 2002 11 01

0026-8925 253 1-2 1996 Nov 27 The gene fl(2)d is needed for the sex-specific splicing of transformer pre-mRNA but not for double-sex pre-mRNA in Drosophila melanogaster. 26-31 In Drosophila melanogaster, regulation of the sex determination genes throughout development occurs by sex-specific splicing of their products. The first gene is Sex-lethal(Sxl). The downstream target of Sxl is the gene transformer (tra): the Sxl protein controls the female-specific splicing of the Tra pre-mRNA. The downstream target of the gene tra is the gene double-sex (dsx): the Tra protein of females, controls the female-specific splicing of the Dsx pre-mRNA. We have identified a gene, female-lethal-2-d fl(2) d, whose function is required for the female-specific splicing of Sxl pre-mRNA. In this report we analyze whether the gene fl(2)d is also required for the sex-specific splicing of both Tra and Dsx pre-mRNAs. We found that the Sxl protein is not sufficient for the female-specific splicing of Tra pre-mRNA, the fl(2)d function also being necessary. This gene, however, is not required for the female-specific splicing of Dsx pre-mRNA. Centro de Investigaciones Biológicas, Madrid, Spain. Granadino B B Penalva L O LO Sánchez L L eng Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA-Binding Proteins 0 Insect Hormones 0 Nuclear Proteins 0 RNA Precursors 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 0 doublesex protein, Drosophila 0 transformer protein, Drosophila IM Animal Animals, Genetically Modified DNA-Binding Proteins genetics Drosophila melanogaster genetics Female Genes, Insect Insect Hormones genetics Male Nuclear Proteins genetics RNA Precursors genetics RNA Splicing RNA-Binding Proteins genetics Sex Characteristics Support, Non-U.S. Gov't Temperature FBrf0054081 92038976 1657706 1991 12 05 1991 12 05 2002 11 01

0016-6723 58 1 1991 Aug The synergistic effect of X-rays and deficiencies in DNA repair in P-M hybrid dysgenesis in Drosophila melanogaster. 15-26 X-rays and deficiencies in DNA repair had a synergistic effect on genetic damage associated with P-element mobility in Drosophila melanogaster. These interactions, using sterility and fecundity as endpoints, were tested in dysgenic males deficient in either excision or post-replication DNA repair. Three sublines of the Harwich P strain were used for the construction of hybrid males. These sublines differ in P-induction ability based on gonadal dysgenesis sterility (GD) and snw mutability tests, in P-element insertion site pattern, and in the types of defective P-elements, such as KP elements, they possess. A lower degree of gonadal dysgenesis was correlated with the presence of KP elements. GD sterility and snw mutability were not always correlated. Dysgenic hybrids originating from the standard reference subline, Harwich(white), were much more sensitive to the post-replication repair than the excision repair defect. In contrast, sterility of hybrids derived from the weak subline was least affected by, and that of hybrids of the strongest subline was most affected by either DNA repair deficiency. The exacerbation by X-rays of the effects of DNA repair deficiencies on genetic damage indicates that both repair mechanisms are required for processing DNA lesions induced by the combined effect of P activity and ionizing radiation. Department of Microbiology and Immunology, New York Medical College, Valhalla 10595. Margulies L L Griffith C S CS eng CA 35580 CA NCI Journal Article

ENGLAND Genet Res 0370741 0 DNA Transposable Elements IM Animal Blotting, Southern Crosses, Genetic DNA Repair DNA Transposable Elements Drosophila melanogaster genetics radiation effects Female Fertility genetics radiation effects Hybridization, Genetic Male Mutagenesis radiation effects Support, U.S. Gov't, P.H.S. FBrf0055575 93046661 1423619 1992 12 11 1992 12 11 2000 12 18

0092-8674 71 4 1992 Nov 13 Characterization of the Drosophila cactus locus and analysis of interactions between cactus and dorsal proteins. 623-35 An oligonucleotide based on the cdc 10/SWI6 repeats of the Drosophila Notch protein was used to isolate other Drosophila genes with these repeats. One of these genes is the cactus locus, 1 of 11 genes required maternally for the establishment in embryos of a gradient of nuclear localization of dorsal protein, a rel-like transcription factor. Previous work showed that in cactus mutants more dorsal protein enters the nucleus in dorsal regions, resulting in a ventralized phenotype. It is now shown that the cactus locus produces two proteins that differ at their carboxy termini; both contain six cdc 10/SWI6 repeats that are sufficient for binding to dorsal and for inhibiting the ability of dorsal to bind DNA. The site on dorsal to which cactus binds was localized to the rel homology domain, where it overlaps with, or is adjacent to, the nuclear localization signal. In vivo the bulk of the cactus protein associated with dorsal is phosphorylated. This, or the association with dorsal, appears to stabilize the maternal cactus protein. Laboratory of Genetics, Rockefeller University, New York, New York 10021. Kidd S S eng GENBANK L03367 L03368 L03369 S47136 S47137 S47164 S47165 S47166 S47167 S47168 S72771 GM25103 GM NIGMS Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 NF-kappa B 0 Nuclear Proteins 0 Oligodeoxyribonucleotides 0 Phosphoproteins 0 dorsal protein, Drosophila 0 lyt-10 protein 149059-01-8 cactus protein, Drosophila IM Amino Acid Sequence Animal Base Sequence Binding Sites Cell Line Cloning, Molecular DNA-Binding Proteins chemistry genetics metabolism Drosophila melanogaster genetics metabolism Female Male Molecular Sequence Data NF-kappa B metabolism Nuclear Proteins metabolism Oligodeoxyribonucleotides genetics Phosphoproteins chemistry genetics metabolism Precipitin Tests Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0087607 96109303 8612958 1996 06 06 1996 06 06 2000 12 18

0012-1606 172 2 1995 Dec mRNA localisation during development. 377-95 Although there are many differences, mRNA localisations in the Xenopus oocyte show some tantalizing similarities to those occurring in Drosophila development. As in Drosophila, transcripts localise to opposite poles of the oocyte, this localisation is hierarchical and occurs in a multistep process in which localisation is followed by anchoring at the cortex. This distinction between initial transport and long-term maintenance reflects the dynamic nature of the cytoskeleton: the microtubule tracks form and reform according to the needs of the cell so that stable localisation must be mediated by a more constant structure--the cortex. A possible exception is the localisation of gurken mRNA where it is unknown whether there are separate mechanisms for transport to and maintenance at the oocyte nucleus. However, gurken is responsible for the transmission of a transitory signal; once this has been received, and the fate of the recipient follicle cells determined, there is no further need for localisation. It is possible that the time scale over which the localisation machinery is stable is sufficient for transmission of this signal without the need for a separate maintenance phase. The existence of a nanos homologue, Xcat-2 (Mosquera et al., 1993), associated with the Xenopus germ plasm is particularly interesting because of the morphological and functional similarities between Drosophila polar granules, Caenorhabditis P-granules, and Xenopus germ plasm. These electron-dense protein-RNA complexes are maternally supplied and in each case segregate with the germ line. These granules may represent a fundamental conserved pathway to germ-cell specification and it is now at least a possibility that they are also involved in establishing the embryonic axis through translational repression. In the case of Drosophila, this occurs through localised nanos acting (via Pumilio) on nanos response elements in hunchback mRNA. No such regulatory pair has yet been demonstrated in C. elegans or X. laevis, but each contains a candidate for one half of the interaction: glp-1 could be a target for an unidentified nanos-like protein; Xcat-2 may control translation of an unknown NRE-containing mRNA. Another common feature of mRNA localisation is that in every case where the targeting signal has been determined, it has been mapped to a region of the 3' UTR capable of forming an extensive secondary structure (e.g., David and Ish-Horowicz, 1991; Dalby and Glover, 1992; Gavis and Lehmann, 1992; Kim-Ha et al., 1993; Kislauskis et al., 1993, 1994; Lantz and Schedl, 1994). In several cases, translational control and transcript stability signals have also been mapped to these regions (Jackson and Standart, 1990; Standart et al., 1990; Standart and Hunt, 1990; Davis and Ish-Horowicz, 1991; Wharton and Struhl, 1991; Dalby and Glover, 1993; Evans et al., 1994; Kim-Ha et al., 1995). The large secondary structures may provide a means for stably exposing sequence-specific regions of RNA to proteins. Due to the ease with which RNA forms base pairs, it is likely that rather than remaining single-stranded, RNA within the cell forms some sort of secondary structure. The geometry of purely double-stranded RNA does not permit sequence specific interactions between proteins and the bases because the major groove is inaccessible to amino acid side chains (Weeks and Crothers, 1993). However, the distortions to the dsRNA helix provided by bulges, pseudoknots, and the single-strand loop regions in stem-loop structures do present sequence information that can be "read" by proteins. The extensive 3'UTRs may produce a stable secondary structure which ensures that regulatory elements remain exposed in such regions rather than hidden in double-stranded stems. (ABSTRACT TRUNCATED) Wellcome/CRC Institute, University of Cambridge, United Kingdom. Micklem D R DR eng Journal Article Review Review, Tutorial

UNITED STATES Dev Biol 0372762 0 Proteins 0 RNA, Messenger IM Animal Drosophila melanogaster embryology metabolism Oocytes metabolism Proteins metabolism RNA, Messenger analysis Support, Non-U.S. Gov't Xenopus embryology metabolism 165 FBrf0092613 97176440 9023986 1997 03 07 1997 03 07 2000 12 18

0192-253X 19 4 1996 Engrailed gene dosage determines whether certain recessive cubitus interruptus alleles exhibit dominance of the adult wing phenotype in Drosophila. 340-9 The cubitus interruptus (ci) locus of Drosophila melanogaster is needed for normal development. Some mutants of this gene result in embryonic lethality, while others just disrupt adult wing veins. While undertaking a genetic screen for additional ci mutations that affect the wing veins, we recovered a modifier mutation on chromosome two that produced a ci phenotype in recessive ci heterozygotes (ci(recessive)/+). We identified the modifier mutation as an allele of engrailed and have called it engrailed-enhancer of cubitus interruptus (enEnci). As a double heterozygote (en-/+; ci-/+) this new en allele dominantly generates a ci wing vein phenotype. As a double heterozygote, it also enhances the ci wing vein phenotype of the dominant alleles ciW and ciCe2, but not ciD. Other loss-of-function en alleles also enhance the ci phenotype, with the en lethal alleles (and deletions) showing the strongest effect, while the homozygous viable en alleles show weaker enhancement. Strong en- alleles failed to induce a ci phenotype with heterozygotes of ci recessive lethal alleles l(4)13, l(4)17, or ciDrev, which are loss-of-function mutations. This supports a previous proposal that the ci wing vein phenotype is not due to loss of ci+ function, as would be expected for most recessive alleles. Instead, the adult wing vein abnormality is due to ectopic expression (or de-repression) of the ci transcript in the posterior compartment of the wing disc. We also observed that en-/+ heterozygotes could induce a ci phenotype in situations where the ci+ locus is either unpaired or hemizygous. Since loss of one en+ gene dose enhanced the ci phenotype, three doses of en+ were tested and found to suppress expression of the ci phenotype in ci1 homozygotes and ciW heterozygotes. These observations show that correct regulation of the ci gene involves more than the simple interaction of upstream regulatory elements. some pairing, pairing dependent gene repression, position effects. Department of Biological Sciences, University of Alberta, Edmonton, Canada. Locke J J Hanna S S eng Journal Article

UNITED STATES Dev Genet 7909963 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Hormones 0 Transcription Factors 0 cubitus interruptus protein 0 engrail protein, Drosophila IM Alleles Animal Chromosome Mapping DNA-Binding Proteins genetics Drosophila melanogaster growth & development Gene Dosage Gene Expression Regulation, Developmental physiology Gene Rearrangement Genes, Dominant Genes, Insect Genes, Recessive Heterozygote Homeodomain Proteins genetics Homozygote Insect Hormones genetics Mutation Phenotype Support, Non-U.S. Gov't Transcription Factors genetics Veins abnormalities Wing blood supply FBrf0038927 84023663 6414457 1983 11 23 1983 11 23 2000 12 18

0006-2928 21 7-8 1983 Aug Characterization of a low-activity allele of NADP+-dependent isocitrate dehydrogenase from Drosophila melanogaster. 725-33 We have characterized biochemical effects of IdhGB1 in Drosophila melanogaster. This is a "null"-activity allele for NADP+-dependent isocitrate dehydrogenase (NADP-IDH) isolated from a natural population. The homozygous mutant strain has 5% of the NADP-IDH specific activity found in controls and less than 24% of the immunologically cross-reacting material (CRM). This mutation maps to 27.2 on the third chromosome, to the right of h. The biochemical phenotype of this mutant strain includes a coordinate reduction in malic enzyme (ME) specific activity and CRM and an increase in specific activity for the pentose-phosphate shunt enzymes, 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase. The Km values for purified NADP-IDH are not different from those found for the purified control enzyme for NADP+ or isocitrate. It is suggested that this allele may represent a cis-acting control mutation for one of at least two loci involved in the production of NADP-IDH in D. melanogaster. Bentley M M MM Meidinger R G RG Williamson J H JH eng Journal Article

UNITED STATES Biochem Genet 0126611 53-59-8 NADP EC 1.1.1.37 Malate Dehydrogenase EC 1.1.1.41 Isocitrate Dehydrogenase EC 1.1.1.43 Phosphogluconate Dehydrogenase EC 1.1.1.49 Glucosephosphate Dehydrogenase IM Alleles Animal Chromosome Mapping Comparative Study Drosophila melanogaster enzymology genetics Female Glucosephosphate Dehydrogenase genetics Isocitrate Dehydrogenase genetics Malate Dehydrogenase genetics Male NADP pharmacology Phosphogluconate Dehydrogenase genetics Support, Non-U.S. Gov't FBrf0127340 20243730 10781057 2000 05 24 2000 05 24 2000 12 18

0027-8424 97 9 2000 Apr 25 Divergence of larval morphology between Drosophila sechellia and its sibling species caused by cis-regulatory evolution of ovo/shaven-baby. 4530-4 We report an extreme morphological difference between Drosophila sechellia and related species of the pattern of hairs on first-instar larvae. On the dorsum of most species, the posterior region of the anterior compartment of most segments is covered by a carpet of fine hairs. In D. sechellia, these hairs have been lost and replaced with naked cuticle. Genetic mapping experiments and interspecific complementation tests indicate that this difference is caused, in its entirety, by evolution at the ovo/shaven-baby locus. The pattern of expression of the ovo/shaven-baby transcript is correlated with this morphological change. The altered dorsal cuticle pattern is probably caused by evolution of the cis-regulatory region of ovo/shaven-baby in the D. sechellia lineage. Laboratory for Development and Evolution, University Museum of Zoology, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom. Sucena E E Stern D L DL eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA-Binding Proteins 0 Transcription Factors 0 ovo protein IM Animal Body Patterning Crosses, Genetic DNA-Binding Proteins genetics Drosophila anatomy & histology genetics growth & development Drosophila melanogaster genetics Evolution Evolution, Molecular Female Genes, Insect Genetic Complementation Test Larva Male Phylogeny Species Specificity Support, Non-U.S. Gov't Transcription Factors genetics X Chromosome FBrf0058132 93209210 8096172 1993 04 23 1993 04 23 2003 06 16

0261-4189 12 3 1993 Mar Cell-type-specific mechanisms of transcriptional repression by the homeotic gene products UBX and ABD-A in Drosophila embryos. 1099-109 The homeotic genes of Drosophila melanogaster, which are required for specification of segmental identities, encode proteins capable of regulating gene expression. We have chosen to study the organization and function of a regulatory target in an attempt to learn how homeotic gene products provide appropriate transcriptional controls. We identified 30 common binding sites for the proteins encoded by the Ultrabithorax (Ubx) and abdominal-A (abd-A) genes within a negatively regulated target, the P2 promoter of the Antennapedia (Antp) gene. By systematically mutagenizing binding sites and observing the resulting P2 expression pattern in embryos, we have found evidence for cell-type-specific interactions that are mediated by these sequences. In certain neuronal cells, UBX and ABD-A proteins appear to repress by competing for common binding sites with another homeodomain protein, which we propose to be ANTP acting to induce P2 transcription in an autoregulatory manner. In sets of cells that contribute to the tracheal system, UBX and ABD-A repress by counteracting the function of a factor acting at independent sites. The latter mechanism of repression requires only that multiple homeodomain binding sequences be present and is not dependent on any particular binding site. Department of Human Genetics, Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112. Appel B B Sakonju S S eng CA09602 CA NCI Journal Article

ENGLAND EMBO J 8208664 0 Antennapedia homeodomain protein 0 DNA-Binding Proteins 0 Nuclear Proteins 0 Proteins 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila 9007-49-2 DNA IM Antp Ubx abd-A Animal Base Sequence Binding Sites DNA DNA-Binding Proteins genetics metabolism Drosophila melanogaster Genes, Homeobox Larva Molecular Sequence Data Nuclear Proteins genetics metabolism Promoter Regions (Genetics) Proteins genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0132264 20578814 11136982 2001 01 10 2001 01 25 2002 11 01

0092-8674 103 6 2000 Dec 8 Gradient formation of the TGF-beta homolog Dpp. 981-91 Secreted morphogens such as the Drosophila TGF-beta homolog Decapentaplegic (Dpp) are thought to spread through target tissues and form long-range concentration gradients providing positional information. Using a GFP-Dpp fusion, we monitored a TGF-beta family member trafficking in situ throughout the target tissue and forming a long-range concentration gradient. Evidence is presented that long-range Dpp movement involves Dpp receptor and Dynamin functions. We also show that the rates of endocytic trafficking and degradation determine Dpp signaling range. We propose a model where the gradient is formed via intracellular trafficking initiated by receptor-mediated endocytosis of the ligand in receiving cells with the gradient slope controlled by endocytic sorting of Dpp toward recycling versus degradation. Max-Planck-Institut für molekulare Zellbiologie und Genetik Pfotenhauerstrasse, 108 D-01307, Dresden, Germany. Entchev E V EV Schwabedissen A A González-Gaitán M M eng Journal Article

UNITED STATES Cell 0413066 0 Insect Proteins 0 Luminescent Proteins 0 Recombinant Fusion Proteins 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 147336-22-9 green fluorescent protein EC 3.6.1.- GTP Phosphohydrolases EC 3.6.1.- rab GTP-Binding Proteins EC 3.6.1.50 Dynamins IM Animal Animals, Genetically Modified Body Patterning Drosophila melanogaster anatomy & histology embryology physiology Dynamins Endocytosis Endosomes metabolism GTP Phosphohydrolases genetics metabolism Genes, Reporter Immunohistochemistry Insect Proteins genetics metabolism Luminescent Proteins genetics metabolism Protein Transport physiology Recombinant Fusion Proteins metabolism Support, Non-U.S. Gov't Temperature Transforming Growth Factor beta chemistry metabolism Wing anatomy & histology physiology rab GTP-Binding Proteins genetics metabolism FBrf0039225 83132835 6402401 1983 04 07 1983 04 07 2000 12 18

0012-1606 95 2 1983 Feb The dual functions of a sex determination gene in Drosophila melanogaster. 512-7 The wild-type function of the sex transforming gene transformer-2 (tra-2) is shown to be required for normal spermatogenesis in XY males. A temperature-shift experiment using the tra-2ts2 allele suggests that tra-2+ must function during the middle stages of spermatogenesis to ensure development of functional sperm. Our results, taken together with those of T. Schüpbach (1982, Dev. Biol. 89, 117-127) indicate that the tra-2+ gene functions in the male germ line and thus, in contrast to all other sex determination loci examined to date (doublesex, intersex, transformer), its action is not limited to the soma. Orcein-stained testis preparations from tra-2 males reveal a spermiogenic defect similar to that associated with dominant male sterile (X; autosome) translocations. Belote J M JM Baker B S BS eng GM07199 GM NIGMS GM23345 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 IM Animal Drosophila melanogaster genetics Female Genotype Heat Infertility, Male genetics Male Mutation Phenotype Sex Determination (Analysis) Sperm Head ultrastructure Spermatogenesis Support, U.S. Gov't, P.H.S. FBrf0059127 93196703 7680770 1993 04 13 1993 04 13 2002 11 01

0028-0836 362 6416 1993 Mar 11 The protein Sex-lethal antagonizes the splicing factor U2AF to regulate alternative splicing of transformer pre-mRNA. 171-5 Somatic sexual differentiation in Drosophila melanogaster involves a cascade of regulated splicing events and provides an attractive model system for the analysis of alternative splicing mechanisms. The protein Sex-lethal (Sxl) activates a female-specific 3' splice site in the first intron of transformer (tra) pre-mRNA while repressing an alternative non-sex-specific site. We have developed an in vitro system that recapitulates this regulation in a manner consistent with genetic, transfection and fly transformation studies. Using this system, we have determined the molecular basis of the splice site switch. Here we show that Sxl inhibits splicing to the non-sex-specific (default) site by specifically binding to its polypyrimidine tract, blocking the binding of the essential splicing factor U2AF. This enables U2AF to activate the lower-affinity female-specific site. A splicing 'effector' domain present in U2AF but absent from Sxl accounts for the different activities of these two polypyrimidine-tract-binding proteins: addition of the U2AF effector domain to Sxl converts it from a splicing repressor to an activator and renders it unable to mediate splice-site switching. Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605. Valcárcel J J Singh R R Zamore P D PD Green M R MR eng Journal Article

ENGLAND Nature 0410462 0 Insect Hormones 0 RNA Precursors 0 Recombinant Proteins 0 Ribonucleoproteins 0 Sxl protein, Drosophila 0 splicing factor U2AF 63231-63-0 RNA 9004-22-2 Globins IM Sxl tra Alternative Splicing Animal Animals, Genetically Modified Base Sequence Comparative Study Drosophila melanogaster genetics physiology Female Genes, Lethal Globins genetics Human Insect Hormones metabolism Introns Male Molecular Sequence Data Polymerase Chain Reaction methods RNA genetics isolation & purification RNA Precursors genetics metabolism RNA Splicing Recombinant Proteins metabolism Ribonucleoproteins metabolism Sex Ratio Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0134557 21124990 11222155 2001 03 06 2001 04 26 2002 11 01

0950-1991 128 6 2001 Mar A lesson from flex: consider the Y chromosome when assessing Drosophila sex-specific lethals. 1015-8 Bhattacharya et al. (Bhattacharya, A., Sudha, S., Chandra, H. S. and Steward, R. (1999) Development 126, 5485-5493) reported that loss-of-function mutations in the flex (female-specific lethal on X) gene caused female-specific lethality because flex(+) acts as a positive regulator of the master switch gene Sex lethal (Sxl). Sxl is essential for female development. Key to their conclusion was the ability of flex mutations to suppress the male lethality caused by Sxl(M) mutations, which inappropriately activate Sxl female-specific expression. Here we report our contrary findings that flex mutations fail to suppress even the weakest Sxl(M )alleles, arguing against the proposed regulatory relationship between flex and Sxl. Instead we show that the lethal flex phenotype depends on the absence of a Y chromosome, not on the presence of two X chromosomes. flex lethality is caused by a defect in the functioning of the X-linked rDNA locus called bobbed, since this defect is complemented by the corresponding wild-type rDNA complex on the Y. Department of Molecular and Cell Biology, Division of Genetics and Development, University of California, Berkeley, Berkeley, CA 94720-3204, USA. sxlcline@uclink.berkeley.edu Cline T W TW eng Journal Article

England Development 8701744 0 Insect Hormones 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Abdomen Alleles Animal Chromosome Mapping Drosophila melanogaster genetics Female Genes, Lethal Genotype Insect Hormones genetics Male Phenotype RNA-Binding Proteins genetics Sex Differentiation Suppression, Genetic X Chromosome Y Chromosome FBrf0100320 98105113 9442902 1998 02 18 1998 02 18 2000 12 18

0066-4197 31 1997 Germline cyst formation in Drosophila. 405-28 In a wide variety of organisms, gametes develop within clusters of interconnected germline cells called cysts. Four major principles guide the construction of most cysts: synchronous division, a maximally branched pattern of interconnection between cells, specific changes in cyst geometry, and cyst polarization. The fusome is a germline-specific organelle that is associated with cyst formation in many insects and is likely to play an essential role in these processes. This review examines the cellular and molecular processes that underlie fusome formation and cyst initiation, construction, and polarization in Drosophila melanogaster. The studies described here highlight the importance of cyst formation to the subsequent development of functional gametes. Howard Hughes Medical Institute/Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA. de Cuevas M M Lilly M A MA Spradling A C AC eng GM27875 GM NIGMS Journal Article Review Review, Tutorial

UNITED STATES Annu Rev Genet 0117605 IM Animal Cell Differentiation Drosophila melanogaster cytology physiology Germ Cells cytology physiology Human Morphogenesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 94 FBrf0084099 96024624 7575529 1995 11 02 1995 11 02 2000 12 18

0006-291X 214 3 1995 Sep 25 Calcium destabilises Drosophila cactus protein and dephosphorylates the dorsal transcription factor. 1191-6 The Drosophila cactus and dorsal proteins are required for the development of embryonic dorso-ventral polarity and probably also for the innate immune response of the insect. Like their mammalian counterparts (the cytoplasmic anchor protein I kappa B and the rel/NF kappa B transcription factors) cactus and dorsal are regulated at the level of nuclear localisation. We showed previously that increased intra-cellular calcium levels induced by the ionophore ionomycin can activate dorsal/cactus complexes in the Drosophila cell line SL2. In order to study further the activation of dorsal/cactus complexes by calcium, we have prepared a cell line (SLDL) in which dorsal is expressed constitutively. In this paper we show that in SLDL cells ionomycin induces a rapid destruction of cactus and dephosphorylation of dorsal. These results suggest a role for the protein phosphatase calcineurin in calcium mediated activation of dorsal/cactus complexes. They also indicate that in the resting cell constitutive phosphorylation of dorsal is in equilibrium with calcium dependent dephosphorylation. Department of Biochemistry, University of Cambridge, UK. Kubota K K Gay N J NJ eng Journal Article

UNITED STATES Biochem Biophys Res Commun 0372516 0 DNA-Binding Proteins 0 Nuclear Proteins 0 Phosphoproteins 0 Transcription Factors 0 dorsal protein, Drosophila 149059-01-8 cactus protein, Drosophila 56092-81-0 Ionomycin 7440-70-2 Calcium IM Amino Acid Sequence Animal Blotting, Western Calcium pharmacology Cell Line Comparative Study Conserved Sequence DNA-Binding Proteins chemistry drug effects metabolism Drosophila melanogaster embryology Embryo, Nonmammalian Ionomycin pharmacology Molecular Sequence Data Nuclear Proteins drug effects metabolism Phosphoproteins chemistry drug effects metabolism Phosphorylation Sequence Homology, Amino Acid Support, Non-U.S. Gov't Transcription Factors metabolism FBrf0065498 94139491 8306827 1994 03 11 1994 03 11 2000 12 18

0009-5915 102 9 1993 Nov HSP90 associates with specific heat shock puffs (hsr omega) in polytene chromosomes of Drosophila and Chironomus. 648-59 The heat shock protein HSP90, which is mainly cytoplasmic, has recently been reported to be present in the nucleus. We have found a specific chromosomal localization of HSP90 in different species of Drosophila and Chironomus using immunocytochemical techniques with different mono- and polyclonal antibodies for this hsp. HSP90 was found associated with heat shock-induced puffs at 93D and 48B in salivary gland chromosomes of Drosophila melanogaster and Drosophila hydei, respectively. The localization of HSP90 to locus 93D occurred rapidly after the onset of heat shock and disappeared during recovery, concomitant with puff regression. The association of HSP90 with the 93D locus was strictly heat shock dependent as shown by the absence of HSP90 in puff 93D induced by either benzamide or colchicine. No specific nuclear staining was observed in unstressed control cells. HSP90 was also found in the temperature-induced telomeric Balbiani ring puffs (T-BRs) in Chironomus thummi and in one heat shock puff at I-1C in Chironomus tentans. Other heat shock puffs also appeared lightly stained with the HSP90 polyclonal antibody in both species of Chironomus. HSP90 was absent from the T-BRs when RNA synthesis was inhibited with Actinomycin D suggesting that the localization of HSP90 is dependent on transcription. Inhibition of protein synthesis did not prevent association of this hsp with the T-BRs, indicating that pre-existing HSP90 can associate with this locus. HSP90 did not associate with any telomeric chromosomal regions of unstressed cells. The present observations suggest that heat shock gene products such as HSP90 may somehow be involved in the regulation at the chromosomal level of other members of the heat shock gene family. Puffs 93D (D. melanogaster) and 48B (D. hydei) are equivalent and correspond to homologous gene loci (hsr omega) that have unusual features that distinguish them from other heat shock puffs. The binding of HSP90 at T-BRs and at puff I-1C in the genus Chironomus is the first demonstration, albeit indirect, of the existence of hsr omega analogous loci in species other than Drosophila. Centro de Investigaciones Biologicas, CSIC, Madrid, Spain. Morcillo G G Diez J L JL Carbajal M E ME Tanguay R M RM eng Journal Article

GERMANY Chromosoma 2985138R 0 Heat-Shock Proteins IM hsr omega Animal Binding Sites Chironomidae genetics metabolism ultrastructure Chromosomes metabolism ultrastructure Comparative Study Drosophila genetics metabolism ultrastructure Drosophila melanogaster genetics metabolism ultrastructure Genes, Insect Heat Heat-Shock Proteins metabolism Species Specificity Support, Non-U.S. Gov't Transcription, Genetic Translation, Genetic FBrf0080370 95157517 7854313 1995 03 16 1995 03 16 2001 11 02

0026-8925 246 3 1995 Feb 6 Characterization of a region of the X chromosome of Drosophila including multi sex combs (mxc), a Polycomb group gene which also functions as a tumour suppressor. 282-90 Genetic analysis of the 8D3;8D8-9 segment of the Drosophila melanogaster X chromosome has assigned seven complementation groups to this region, three of which are new. A Polycomb group (Pc-G) gene, multi sex combs (mxc), is characterized and mutant alleles are described. Besides common homeotic transformations characteristic of Pc-G mutants that mimic the ectopic gain of function of BX-C and ANT-C genes, mxc mutants show other phenotypes: they zygotically mimic, in males and females, the characteristic lack of germ line seen in progeny of some maternal effect mutants of the so-called posterior group (the grandchildless phenotype). Loss of normal mxc function can promote uncontrolled malignant growth which indicates a possible relationship between Pc-G genes and tumour suppressor genes. We propose that gain-of-function of genes normally repressed by the wild-type mxc product could, in mxc mutants, give rise to an incoherent signal which would be devoid of meaning in normal development. Such a signal could divert somatic and germ line development pathways, provoke the loss of cell affinities, but allow or promote growth. Centre de Génétique Moléculaire du C.N.R.S., Gif sur Yvette, France. Santamaría P P Randsholt N B NB eng Journal Article

GERMANY Mol Gen Genet 0125036 0 Proteins 134549-01-2 Polycomb protein, insect IM Alleles Animal Crosses, Genetic Drosophila melanogaster genetics growth & development Female Genes, Dominant Genes, Insect physiology Genes, Lethal Genes, Tumor Suppressor physiology Infertility, Female genetics Infertility, Male genetics Male Mutagenesis Phenotype Proteins genetics Support, Non-U.S. Gov't X Chromosome FBrf0151326 22148755 12154120 2002 08 02 2002 09 05 2002 11 01

0890-9369 16 15 2002 Aug 1 RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E. 1884-9 Gene silencing by double-stranded RNA is a widespread phenomenon called RNAi, involving homology-dependent degradation of mRNAs. Here we show that RNAi is established in the Drosophila female germ line. mRNA transcripts are translationally quiescent at the arrested oocyte stage and are insensitive to RNAi. Upon oocyte maturation, transcripts that are translated become sensitive to degradation while untranslated transcripts remain resistant. Mutations in aubergine and spindle-E, members of the PIWI/PAZ and DE-H helicase gene families, respectively, block RNAi activation during egg maturation and perturb translation control during oogenesis, supporting a connection between gene silencing and translation in the oocyte. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA. Kennerdell Jason R JR Yamaguchi Shinji S Carthew Richard W RW eng Journal Article

United States Genes Dev 8711660 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Peptide Initiation Factors 0 RNA, Double-Stranded 0 RNA, Messenger 0 RNA, Small Interfering 0 RNA, Untranslated 0 Transcription Factors 0 aubergine protein, Drosophila 0 hunchback protein, Drosophila EC 2.7.7.- RNA Helicases EC 2.7.7.- spindle-E protein, Drosophila IM Animal DNA-Binding Proteins genetics Drosophila Proteins genetics physiology Drosophila melanogaster embryology genetics Female Gene Silencing physiology Microinjections Oocytes metabolism Oogenesis genetics Peptide Initiation Factors genetics physiology Protein Structure, Tertiary RNA Helicases genetics physiology RNA, Double-Stranded administration & dosage metabolism pharmacology RNA, Messenger genetics metabolism RNA, Small Interfering RNA, Untranslated metabolism Support, Non-U.S. Gov't Transcription Factors genetics Transcription, Genetic Translation, Genetic FBrf0093645 97321547 9178257 1997 07 29 1997 07 29 2002 10 21

0925-4773 63 1 1997 Apr The dynamics of neurogenic signalling underlying bristle development in Drosophila melanogaster. 61-74 We have examined expression of the neurogenic gene, Delta (Dl), and the regulatory relationships between the Delta-Notch signalling pathway and the proneural gene, achaete, during microchaeta development in Drosophila. Delta is expressed in all microchaeta proneural cells and microchaeta sensory organ precursors (SOPs) and is expressed dynamically in SOP progeny. We find that Delta expression in microchaeta proneural cells is detected prior to the onset of achaete expression and arises normally in the absence of achaete/scute function, indicating that initial Delta expression in the notum is not dependent on proneural gene function. Activation of the Delta-Notch pathway results in loss of Delta protein accumulation, suggesting that Delta expression is regulated, in part, by Delta-Notch signalling activity. We find that Delta signalling is required for correct delineation of early proneural gene expression in developing nota. Within microchaeta proneural stripes, we demonstrate that Delta-Notch signalling prohibits adoption of the SOP fate by repressing expression of proneural genes. Department of Biology, Indiana University, Bloomington 47405, USA. Parks A L AL Huppert S S SS Muskavitch M A MA eng GM33291 GM NIGMS Journal Article

IRELAND Mech Dev 9101218 0 DNA Transposable Elements 0 DNA-Binding Proteins 0 Membrane Proteins 0 Transcription Factors 0 achaete protein, Drosophila 0 delta protein IM Animal Animals, Genetically Modified DNA Transposable Elements DNA-Binding Proteins biosynthesis Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Genes, Insect Membrane Proteins biosynthesis Nervous System Physiology Pupa Receptors, Sensory physiology Signal Transduction Support, U.S. Gov't, P.H.S. Transcription Factors biosynthesis Vibrissae growth & development ultrastructure FBrf0044468 86275948 3089869 1986 09 18 1986 09 18 2000 12 18

0016-6731 113 3 1986 Jul The genetics of the dorsal-Bicaudal-D region of Drosophila melanogaster. 665-78 The chromosomal region 36C on 2L contains two maternal-effect loci, dorsal (dl) and Bicaudal-D (Bic-D), which are involved in establishing polarity of the Drosophila embryo along the dorsal-ventral and anterior-posterior axes, respectively. To analyze the region genetically, we isolated X-ray-induced dorsal alleles, which we recognized by virtue of the haplo-insufficient temperature-sensitive dorsal-dominant phenotype in progeny of single females heterozygous for a mutagenized chromosome. From the 20,000 chromosomes tested, we isolated three deficiencies, two inversions with breakpoint in dl and one apparent dl point mutant. One of the deficiencies, Df(2L)H20 (36A6,7; 36F1,2) was used to screen for EMS-induced lethal- and maternal-effect mutants mapping in the vicinity of dl and Bic-D. We isolated 44 lethal mutations defining 11 complementation groups. We also recovered as maternal-effect mutations four dl alleles, as well as six alleles of quail and one allele of kelch, two previously identified maternal-effect genes. Through complementation tests with various viable mutants and deficiencies in the region, a total of 18 loci were identified in an interval of about 30 cytologically visible bands. The region was subdivided into seven subregions by deficiency breakpoints. One lethal complementation group as well as the two maternal loci, Bic-D and quail, are located in the same deficiency interval as is dl. Steward R R Nüsslein-Volhard C C eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Aberrations Chromosome Mapping Crosses, Genetic Drosophila melanogaster embryology genetics radiation effects Female Genetic Complementation Test Homozygote Male Mutation Recombination, Genetic Support, U.S. Gov't, P.H.S. X-Rays FBrf0144737 21827156 11838530 2002 02 12 2002 04 16 2002 11 01

0001-8244 31 6 2001 Nov The genetics of cognitive processes: candidate genes in humans and animals. 511-31 It has been hypothesized that numerous genes contribute to individual variation in human cognition. An extensive search of the scientific literature was undertaken to identify candidate genes which might contribute to this complex trait. A list of over 150 candidate genes that may influence some aspect of cognition was compiled. Some genes are particularly strong candidates based on evidence for involvement in cognitive processes in humans, mice, and Drosophila melanogaster. This survey confirms that many genes are associated with cognitive variation and highlights the potential importance of animal models in the study of human cognition. Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia. Morley K I KI Montgomery G W GW eng Journal Article Review Review, Tutorial

United States Behav Genet 0251711 0 Genetic Markers IM Animal Chromosome Mapping Drosophila melanogaster Genetic Markers genetics Human Intelligence genetics Mental Retardation genetics Mice Phenotype Quantitative Trait, Heritable 190 FBrf0136868 21325949 11432740 2001 07 02 2001 09 13 2002 12 13

0014-2956 268 13 2001 Jul SP3 and AP-1 mediate transcriptional activation of the lamin A proximal promoter. 3736-43 Lamin A is a major component of the nuclear lamina that is expressed in various types of differentiated cells. We have analysed previously the putative promoter sequences of the gene and shown that the rat lamin A proximal promoter contains two essential motifs, a GC box that can bind to Sp1 and Sp3, and an AP-1 motif that can bind to c-Jun and c-Fos. In this study we have investigated the role of Sp1 and Sp3 in transactivation of the promoter. Functional analysis of the promoter in Drosophila SL2 cells has demonstrated that it is inactive in the absence of Sp proteins. Activation by expression of Sp3 is more pronounced than that by Sp1 although both proteins can bind to the GC box in vitro; activation clearly depends on an intact GC box as deduced from mutant analysis. Promoter activity in SL2 cells also requires an intact AP-1 motif, which can bind to endogenous Drosophila Jun and Fos proteins. Furthermore, overexpression of c-Jun and c-Fos results in fourfold activation of the promoter in PCC-4 embryonal carcinoma cells. Our demonstration that activation of the lamin A proximal promoter is mediated by Sp3 and AP-1 transcription factors affords a basis for further studies on the regulation of this important gene during development and disease. Centre for Cellular and Molecular Biology, Hyderabad, India. Muralikrishna B B Parnaik V K VK eng Journal Article

Germany Eur J Biochem 0107600 0 DNA-Binding Proteins 0 Lamin Type A 0 Lamins 0 Nuclear Proteins 0 Proto-Oncogene Proteins c-fos 0 Proto-Oncogene Proteins c-jun 0 Recombinant Proteins 0 Transcription Factor AP-1 0 Transcription Factors 148710-94-5 transcription factor Sp3 EC 1.13.12.- Luciferase IM Animal Base Sequence Binding Sites Cell Line DNA Mutational Analysis DNA-Binding Proteins metabolism Drosophila melanogaster Genes, Reporter Lamin Type A Lamins Luciferase genetics Molecular Sequence Data Nuclear Proteins genetics Promoter Regions (Genetics) Proto-Oncogene Proteins c-fos metabolism Proto-Oncogene Proteins c-jun metabolism Rats Recombinant Proteins biosynthesis TATA Box Trans-Activation (Genetics) Transcription Factor AP-1 metabolism Transcription Factors metabolism Transcription, Genetic Transfection Zinc Fingers FBrf0132269 21065966 11139280 2001 01 26 2001 06 21

1350-9047 7 11 2000 Nov Eggs to die for: cell death during Drosophila oogenesis. 1071-4 Extensive programmed cell death occurs in the female germline of many species ranging from C. elegans to humans. One purpose for germline apoptosis is to remove defective cells unable to develop into fertile eggs. In addition, recent work suggests that the death of specific germline cells may also play a vital role by providing essential nutrients to the surviving oocytes. In Drosophila, the genetic control of germline apoptosis and the proteins that carry out the death sentences are beginning to emerge from studies of female sterile mutations. These studies suggest that the morphological changes that occur during the late stages of Drosophila oogenesis may be initiated and driven by a modified form of programmed cell death. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA. Buszczak M M Cooley L L eng GM43301 GM NIGMS Journal Article Review Review, Tutorial

England Cell Death Differ 9437445 IM Animal Apoptosis Biological Transport Drosophila melanogaster genetics physiology Female Human In Situ Nick-End Labeling Oogenesis Ovum cytology physiology Support, U.S. Gov't, P.H.S. 34 FBrf0074380 94261113 7911223 1994 07 05 1994 07 05 2000 12 18

0026-8925 243 4 1994 May 25 Gene inactivation in Drosophila mediated by the Polycomb gene product or by position-effect variegation does not involve major changes in the accessibility of the chromatin fibre. 453-62 In Drosophila position effect variegation and Polycomb-dependent regulation of homeotic gene expression are phenomena in which genes are inactivated in a clonally inherited manner. In both processes inactivation involves proteins that interact with the chromosome at or close to the position of inactivated genes. Two models have been proposed to explain this form of genetic silencing. In one, cooperative concatamerisation of a large multisubunit protein complex packages the chromatin fibre into a higher order structure, which is inaccessible for the transcription apparatus. In the second, the chromatin fibre is left unaltered but the region to be silenced is assigned to a compartment within the nucleus to which not all transcription factors have access. To distinguish between these types of model we have used the ligation-mediated PCR procedure to quantitate the accessibility of restriction sites in the chromatin fibre in both the active and inactivated forms. By making use of appropriate mutations and tissues we show that the inactivation of genes by Polycomb or by position effect variegation is not accompanied by a substantial change in the accessibility of the fibre. These results favour models in which the inactivation is achieved by sequestration of the silenced region in a particular nuclear compartment rather than by a chromatin packaging model. Institut für Genetik, Universität Köln, Germany. Schlossherr J J Eggert H H Paro R R Cremer S S Jack R S RS eng Journal Article

GERMANY Mol Gen Genet 0125036 0 Chromatin 0 Chromosomal Proteins, Non-Histone 0 Heterochromatin 0 Insect Hormones 0 Oligonucleotide Probes 0 Proteins 0 Transcription Factors 126548-29-6 liver-specific transcription factor LF-B1 134549-01-2 Polycomb protein, insect IM Animal Base Sequence Cell Nucleus chemistry ultrastructure Chromatin chemistry ultrastructure Chromosomal Proteins, Non-Histone genetics Chromosomes ultrastructure Drosophila melanogaster genetics Enhancer Elements (Genetics) Eye Color genetics Female Gene Expression Regulation Genes, Homeobox Genes, Insect Genes, Suppressor Heterochromatin chemistry ultrastructure Insect Hormones genetics physiology Linear Models Molecular Sequence Data Mutation Oligonucleotide Probes Phenotype Polymerase Chain Reaction methods Proteins genetics physiology Restriction Mapping Support, Non-U.S. Gov't Transcription Factors FBrf0100057 98090057 9362474 1998 01 30 1998 01 30 2002 11 01

0950-1991 124 24 1997 Dec Induction of female Sex-lethal RNA splicing in male germ cells: implications for Drosophila germline sex determination. 5033-48 With a focus on Sex-lethal (Sxl), the master regulator of Drosophila somatic sex determination, we compare the sex determination mechanism that operates in the germline with that in the soma. In both cell types, Sxl is functional in females (2X2A) and nonfunctional in males (1X2A). Somatic cell sex is determined initially by a dose effect of X:A numerator genes on Sxl transcription. Once initiated, the active state of SXL is maintained by a positive autoregulatory feedback loop in which Sxl protein insures its continued synthesis by binding to Sxl pre-mRNA and thereby imposing the productive (female) splicing mode. The gene splicing-necessary factor (snf), which encodes a component of U1 and U2 snRNPs, participates in this RNA splicing control. Here we show that an increase in the dose of snf+ can trigger the female Sxl RNA splicing mode in male germ cells and can feminize triploid intersex (2X3A) germ cells. These snf+ dose effects are as dramatic as those of X:A numerator genes on Sxl in the soma and qualify snf as a numerator element of the X:A signal for Sxl in the germline. We also show that female-specific regulation of Sxl in the germline involves a positive autoregulatory feedback loop on RNA splicing, as it does in the soma. Neither a phenotypically female gonadal soma nor a female dose of X chromosomes in the germline is essential for the operation of this feedback loop, although a female X-chromosome dose in the germline may facilitate it. Engagement of the Sxl splicing feedback loop in somatic cells invariably imposes female development. In contrast, engagement of the Sxl feedback loop in male germ cells does not invariably disrupt spermatogenesis; nevertheless, it is premature to conclude that Sxl is not a switch gene in germ cells for at least some sex-specific aspects of their differentiation. Ironically, the testis may be an excellent organ in which to study the interactions among regulatory genes such as Sxl, snf, ovo and otu which control female-specific processes in the ovary. Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA. Hager J H JH Cline T W TW eng GM-23468 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 RNA-Binding Proteins 0 Ribonucleoprotein, U1 Small Nuclear 0 SNF protein 0 Sxl protein, Drosophila 0 Transcription Factors 0 ovarian tumor protein, Drosophila 0 ovo protein IM Animal Animals, Genetically Modified Crosses, Genetic DNA-Binding Proteins genetics Drosophila melanogaster genetics Female Gene Dosage Gene Expression Regulation, Developmental genetics Germ Cells physiology Insect Proteins genetics Male Mutation Phenotype Polyploidy RNA Splicing genetics RNA-Binding Proteins genetics Ribonucleoprotein, U1 Small Nuclear genetics Sex Determination (Genetics) Support, U.S. Gov't, P.H.S. Transcription Factors genetics X Chromosome genetics FBrf0082711 95280186 7760212 1995 06 29 1995 06 29 2000 12 18

0167-7063 9 4 1995 Feb Behavioral and pheromonal phenotypes associated with expression of loss-of-function mutations in the sex-lethal gene of Drosophila melanogaster. 219-26 We have shown that female-specific functions of the sex determination gene Sex-lethal (Sxl) regulate sexual behavior and synthesis of the three major sex pheromones that have been identified in normal, sexually mature Drosophilia melanogaster males and virgin females. Diplo-X flies, heterozygous in trans for two partial loss-of-function Sxl mutations, elicit less courtship than normal females and produce large quantities of the inhibitory pheromones that normal males synthesize. In addition, the mutant flies fail to synthesize the female-predominant aphrodisiac pheromone or make very small quantities of this compound. Department of Biology, Temple University, Philadelphia, Pennsylvania 19122, USA. Tompkins L L McRobert S P SP eng GM33511 GM NIGMS Journal Article

ENGLAND J Neurogenet 8406473 0 Sex Attractants IM Sxl Animal Drosophila melanogaster genetics Female Genes, Insect Genes, Lethal Male Mutation Phenotype Sex Attractants biosynthesis Sex Behavior, Animal physiology Sex Characteristics Sex Determination (Analysis) Support, U.S. Gov't, P.H.S. FBrf0049893 90060704 2511069 1990 01 05 1990 01 05 2000 12 18

0016-6731 123 2 1989 Oct The genetics of the Dras3-Roughened-ecdysoneless chromosomal region (62B3-4 to 62D3-4) in Drosophila melanogaster: analysis of recessive lethal mutations. 327-36 The genetic organization of interval 62B3-4 to 62D3-4 on the Drosophila third chromosome was investigated. The region (designated DRE) includes four known loci: Roughened (R; 3-1.4), defined by a dominant mutation disrupting eye morphology; the nonvital locus Aprt, structural gene for adenine phosphoribosyltransferase; Dras3, a homolog of the vertebrate ras oncogene; and 1(3)ecdysoneless (1(3)ecd), a gene that has been implicated in the regulation of larval molting hormone (ecdysteroid) synthesis. Overlapping chromosomal deletions of the region were generated by gamma-ray-induced reversion of the R mutation. Recessive lethal mutations were isolated based upon failure to complement the recessive lethality of Df(3L)RR2, a deletion of the DRE region that removes 16-18 polytene chromosome bands. A total of 117 mutations were isolated following ethyl methanesulfonate and gamma-ray mutagenesis. These and two additional define 13 lethal complementation groups. Mutations at two loci were recovered at disproportionately high rates. One of these loci is preferentially sensitive to radiation-induced mutational alterations. Additionally, an unusually low recovery rate for cytologically detectable rearrangement breakpoints within the gamma-ray-sensitive locus suggests that an interval of the DRE region closely linked to the R locus may be dominantly sensitive to position effects. Lethal phase analysis of mutant hemizygotes indicates that a high proportion of DRE-region loci (11 of 13) are necessary for larval development. Mutations in five loci cause predominantly first-instar larval lethality, while mutations in four other loci cause predominantly second-instar lethality. Mutations in two loci cause late-larval lethality associated with abnormal imaginal disc development. A temperature-sensitive allele of one newly identified complementation group blocks ecdysteroid-induced pupariation. This developmental block is overcome by dietary 20-hydroxyecdysone, suggesting that a second locus in the region in addition to l(3)ecd may play a role in the regulation of late larval ecdysteroid levels. Department of Biology, University of North Carolina, Chapel Hill 27599-3280. Sliter T J TJ Henrich V C VC Tucker R L RL Gilbert L I LI eng DK-35347 DK NIDDK NS-07166 NS NINDS Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Deletion Chromosome Mapping Chromosomes Crosses, Genetic Drosophila melanogaster genetics Female Genes, Lethal Genes, Recessive Genetic Complementation Test Genotype Male Mutation Phenotype Recombination, Genetic Support, U.S. Gov't, P.H.S. FBrf0053055 91118240 1703680 1991 03 01 1991 03 01 2000 12 18

0166-2236 13 12 1990 Dec Genes required for specifying cell fates in Drosophila embryonic sensory nervous system. 493-8 The nervous system contains a diverse group of cells. Specification of the correct cell fate is obviously important for the proper function of the nervous system, yet how are the fates of different neurons determined during development? Very little is known about the underlying molecular mechanisms used in the mammalian nervous system. How, for example, are certain cells directed to form pyramidal cells rather than local interneurons? In the fruit fly Drosophila melanogaster, and the nematode Caenorhabditis elegans, some progress has been made in studying neuronal fate determination. For instance, in Drosophila, a number of genes acting at different levels have been found to control this process. They function to (1) endow a subset of the ectodermal cells in the early embryo with the potential to become neuronal precursors, (2) commit some of these cells to the fate of neuronal precursors, (3) specify the identity of these neuronal precursors, and (4) specify the identity of the individual progeny cells of a neuronal precursor. In this review, we discuss first the rationale of the genetic approach, then outline the working hypothesis and, finally, briefly describe the genes known to be involved in the formation of the sensory nervous system in Drosophila. We also discuss the prospects for extrapolating these molecular mechanisms and principles to vertebrate and invertebrate neural development. Howard Hughes Medical Institute, University of California, San Francisco 94143-0724. Jan Y N YN Jan L Y LY eng Journal Article Review Review, Tutorial

ENGLAND Trends Neurosci 7808616 IM Animal Drosophila embryology genetics Embryo, Nonmammalian physiology Female Genes Male Nervous System embryology Support, Non-U.S. Gov't 69 FBrf0049834 89306625 2501154 1989 08 22 1989 08 22 2000 12 18

0890-9369 3 6 1989 Jun The role of segment polarity genes during Drosophila neurogenesis. 890-904 Segment polarity genes in Drosophila are required for the proper formation of epidermal pattern within each segment. Here we show that certain segment polarity genes are also critical for the determination of specific neuronal identities in the developing central nervous system (CNS) of the Drosophila embryo. For several mutants, however, the pattern defects do not simply parallel their cuticular phenotypes. In fused, armadillo, and cubitus interruptus Dominant mutants, much of the CNS appears relatively normal. In hedgehog mutants, the CNS is highly disorganized, but this disruption may occur secondary to the initial events of neurogenesis. The specific cellular defects in patched mutants suggests that this gene specifies a subset of neuroblasts and neural progeny underlying the region of epidermal pattern defect. gooseberry mutants display a complex series of alterations in neuronal identity both underlying and outside of the region of epidermal modification. Neuronal identities of a set of cells along the midline appear to be changed in Cell mutants. The phenotype of wingless mutants is the most restricted and may be due to improper communication between sibling neurons. Thus, in addition to their functions in epidermal pattern formation, at least four of the segment polarity genes (gooseberry, patched, Cell, and wingless) appear to have specific roles in the control of cell fates during neurogenesis. Howard Hughes Medical Institute, Department of Biochemistry, University of California--Berkeley 94720. Patel N H NH Schafer B B Goodman C S CS Holmgren R R eng R01 NS18366 NS NINDS Journal Article

UNITED STATES Genes Dev 8711660 IM Animal Comparative Study Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Epidermis embryology Gene Expression Regulation Genes, Regulator Morphogenesis Mutation Nervous System embryology Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0095799 97355587 9212068 1997 08 27 1997 08 27 2000 12 18

0022-3034 33 1 1997 Jul Neuronal cAMP-dependent protein kinase type II is concentrated in mushroom bodies of Drosophila melanogaster and the honeybee Apis mellifera. 33-44 In both Drosophila melanogaster and the honeybee Apis mellifera, cyclic adenosine monophosphate (cAMP)-dependent processes have been implicated in mechanisms of learning. This study characterizes the type II cAMP-dependent protein kinase (PKAII), the major target of cAMP in adult animals. In both species, PKAII is restricted to neuronal tissue, in which it accounts for more than 90% of total PKA activity. Although the intensity of PKAII immunoreactivity differs between distinct brain regions, labeling is detectable in all neuropiles and most somata. While the visual neuropiles, the antennal lobes, and structures of the central brain exhibit intermediate immunostaining, the mushroom bodies show high labeling and contain a three- to fourfold higher PKA activity compared to other neuropiles. Since the mushroom bodies are central sites of olfactory learning mediated via cAMP-dependent signaling, the modulatory functions of transmitters on PKA activity in Kenyon cells from the honeybee were tested. Agents which elevate cytoplasmic Ca2+ levels have no effects on PKA activity in cultured Kenyon cells. Dopamine, serotonin, and octopamine, however, cause an increase in PKA activity in Kenyon cells. The modulation of PKA activity by octopamine, the putative transmitter of the unconditioned stimulus in associative olfactory learning in the honeybee, together with the findings on the central role of the cAMP cascade in Drosophila mushroom bodies, suggests a major implication of PKAII-mediated phosphorylation in learning and memory in both Drosophila and Apis. Institut für Neurobiologie der Freien Universität Berlin, Germany. Müller U U eng Journal Article

UNITED STATES J Neurobiol 0213640 104-14-3 Octopamine 50-67-9 Serotonin 51-61-6 Dopamine EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Bees Cells, Cultured Cyclic AMP-Dependent Protein Kinases metabolism Dopamine pharmacology Drosophila melanogaster Interneurons enzymology Nervous System enzymology Neurons cytology enzymology Octopamine pharmacology Organ Specificity Serotonin pharmacology Species Specificity Support, Non-U.S. Gov't FBrf0098471 97398940 9255069 1997 09 05 1997 09 05 2000 12 18

0968-0004 22 7 1997 Jul Phosphoinositide 3-kinases: a conserved family of signal transducers. 267-72 Phosphoinositide 3-kinases (PI3Ks) generate lipids that are implicated in receptor-stimulated signalling and in the regulation of membrane traffic. Several distinct classes of PI3Ks have now been identified that have been conserved throughout eukaryotic evolution. Potential signalling pathways downstream of PI3Ks have been elucidated and PI3K function is now being characterised in several model organisms. Ludwig Institute for Cancer Research, London, UK. Vanhaesebroeck B B Leevers S J SJ Panayotou G G Waterfield M D MD eng GENBANK M59835 M93252 S67334 U03279 U23476 U23477 U23478 U23480 U52192 U52193 U55772 U56101 U57843 U86453 U86587 X53531 X85368 X92892 X99912 Y08991 Y09070 Y10055 Y10742 Y10743 Y11312 Y13367 Y13892 Z29090 Z46973 Z69660 Journal Article Review Review, Tutorial

ENGLAND Trends Biochem Sci 7610674 0 Membrane Lipids EC 2.7.1 Phosphotransferases (Alcohol Group Acceptor) EC 2.7.1.137 1-Phosphatidylinositol 3-Kinase IM 1-Phosphatidylinositol 3-Kinase Animal Caenorhabditis elegans enzymology Dictyostelium enzymology Drosophila melanogaster enzymology Membrane Lipids metabolism Molecular Sequence Data Phosphotransferases (Alcohol Group Acceptor) chemistry classification metabolism Signal Transduction Substrate Specificity Support, Non-U.S. Gov't 53 FBrf0050629 90044103 2554148 1989 12 21 1989 12 21 2000 12 18

0028-0836 342 6247 1989 Nov 16 Requirement of the Drosophila raf homologue for torso function. 288-91 In Drosophila the correct formation of the most anterior and posterior regions of the larva, acron and telson is dependent on the maternally expressed terminal class of genes. In their absence, the anterior head skeleton is truncated and all the structures posterior to the abdominal segment seven are not formed. The protein predicted to be encoded by one of these genes, torso (tor), seems to be a transmembrane protein with an extracytoplasmic domain acting as a receptor and a cytoplasmic domain containing tyrosine kinase activity. Here we report that another member of the terminal-genes class, l(1)polehole (l(1)ph), which is also zygotically expressed, is the Drosophila homologue of the v-raf oncogene and encodes a potential serine-and-threonine kinase. We also show that functional l(1)ph gene product is required for the expression of a gain-of-function tor mutant phenotype, indicating that l(1)ph acts downstream of tor. Together, these results support the idea that the induction of terminal development occurs through a signal transduction system, involving the local activation of the tor-encoded tyrosine kinase at the anterior and posterior egg poles, resulting in the phosphorylation of the l(1)ph gene product. In turn, downstream target proteins may be phosphorylated, ultimately leading to the regionalized expression of zygotic target genes. Such a process is in agreement with the finding that both tor and l(1)ph messenger RNAs are evenly distributed. Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115. Ambrosio L L Mahowald A P AP Perrimon N N eng Journal Article

ENGLAND Nature 0410462 0 DNA Transposable Elements 0 Phosphoproteins 0 Proto-Oncogene Proteins 0 RNA, Messenger EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Animal Blotting, Northern DNA Transposable Elements Drosophila melanogaster embryology genetics Morphogenesis Nucleic Acid Hybridization Oogenesis Phosphoproteins physiology Protein Kinases physiology Proto-Oncogene Proteins physiology Proto-Oncogene Proteins c-raf RNA, Messenger genetics Restriction Mapping Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Transcription, Genetic FBrf0138260 21404206 11513298 2001 08 21 2002 02 07 2003 06 16

0009-5915 110 3 2001 Jul A role of the Drosophila homeless gene in repression of Stellate in male meiosis. 228-40 The homeless gene of Drosophila melanogaster encodes a member of the DE-H family of ATPase and RNA helicase proteins. Loss-of-function homeless mutations were previously found to cause female sterility with numerous defects in oogenesis, including improper formation of both the anterior-posterior and dorsal-ventral axes and failure to transport and localize key RNAs required for axis formation. One homeless mutation was also found to affect male meiosis, causing elevated X-Y nondisjunction. Here we further analyze the role of homeless in male meiosis. We show that homeless mutations cause a variety of defects in male meiosis including nondisjunction of the X-Y and 2-2 pair, Y chromosome marker loss, meiotic drive, chromosome fragmentation, chromatin bridges at anaphase, and tripolar meiosis. In addition, homeless mutations interact with an X chromosomal factor to cause complete male sterility. These phenotypes are similar to those caused by deletion of the Suppressor of Stellate [Su(Ste)] locus. Like Su(Ste) deficiencies, homeless mutants also exhibit crystals in primary spermatocytes and derepression of the X-linked Stellate locus. To determine whether the regulatory role of hls is specific for Stellate or includes other repeated sequences as well, we compared testis RNA levels for nine transposable elements and found that all but one, copia, were expressed at the same levels in hls mutants and wild type. Copia, however, was strongly derepressed in hls mutant males. We conclude that hls functions along with Su(Ste) and other recently described genes to repress the Stellate locus in spermatocytes, and that it may also play a role in repressing certain other repeated sequences. Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville 37996-0840, USA. Stapleton W W Das S S McKee B D BD eng R01 GM40489 GM NIGMS Journal Article

Germany Chromosoma 2985138R 0 DNA Transposable Elements 0 Insect Proteins 9007-49-2 DNA EC 2.7.1.37 Ste protein, Drosophila EC 3.6.1.- homeless protein EC 3.6.1.3 Adenosinetriphosphatase IM Adenosinetriphosphatase genetics Animal Chromosome Segregation Comparative Study DNA genetics physiology DNA Transposable Elements genetics Drosophila melanogaster genetics Gene Expression Regulation Gene Silencing physiology Genes, Insect genetics Genotype Infertility, Male genetics Insect Proteins genetics Male Meiosis genetics Mutation Nondisjunction, Genetic Sex Chromosomes genetics Spermatocytes pathology Support, U.S. Gov't, P.H.S. FBrf0151917 22170646 12183376 2002 08 16 2002 11 08 2003 06 18

0950-1991 129 18 2002 Sep Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila. 4241-8 Malignant transformation frequently involves aberrant signaling from receptor tyrosine kinases (RTKs). These receptors commonly activate Ras/Raf/MEK/MAPK signaling but when overactivated can also induce the JAK/STAT pathway, originally identified as the signaling cascade downstream of cytokine receptors. Inappropriate activation of STAT has been found in many human cancers. However, the contribution of the JAK/STAT pathway in RTK signaling remains unclear. We have investigated the requirement of the JAK/STAT pathway for signaling by wild-type and mutant forms of the RTK Torso (Tor) using a genetic approach in DROSOPHILA: Our results indicate that the JAK/STAT pathway plays little or no role in signaling by wild-type Tor. In contrast, we find that STAT, encoded by marelle (mrl; DStat92E), is essential for the gain-of-function mutant Tor (Tor(GOF)) to activate ectopic gene expression. Our findings indicate that the Ras/Raf/MEK/MAPK signaling pathway is sufficient to mediate the normal functions of wild-type RTK, whereas the effects of gain-of-function mutant RTK additionally require STAT activation. Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. willis_li@URMC.Rochester.edu Li Willis X WX Agaisse Herve H Mathey-Prevot Bernard B Perrimon Norbert N eng R01 GM65774-01 GM NIGMS R01 HL62434 HL NHLBI Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 0 MAP Kinase Signaling System 0 Plasmids 0 STAT92E protein 0 Trans-Activators EC 2.7.1.- TOR protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM Animal Base Sequence Consensus Sequence DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Gene Expression Regulation, Developmental MAP Kinase Signaling System genetics Mutation Plasmids Polymerase Chain Reaction Receptor Protein-Tyrosine Kinases genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism FBrf0111345 99381229 10451922 2000 03 20 2000 03 20 2000 12 18

0965-1748 29 8 1999 Aug A 45-kDa cAMP-dependent phosphoprotein which is related to the product of Mst57Dc in Drosophila melanogaster. 701-10 In Drosophila, the catalytic subunit of cAMP-dependent protein kinase (PKA) is preferentially expressed in the brain and the male reproductive organs. Although the cAMP response element binding protein (CREB) is a major target of PKA in the brain, the target of PKA in the male reproductive organs has been unknown. In the present study, three cAMP-dependent phosphoproteins (referred to as pp45, pp20, and pp10) were detected in the lumen fluid of male accessory glands. They were tissue-specific secretory proteins that accumulated only after eclosion, and were transferred to females during mating as other secretory proteins of the accessory glands. Among them, the 45-kDa phosphoprotein was partially purified and characterized. The purified protein was phosphorylated in vitro by the catalytic subunit of PKA. The partial amino acid sequence of this 45-kDa phosphoprotein was identical to the predicted amino acid sequence of the Mst57Dc cDNA, which is a male accessory gland transcript. Department of Molecular Biology, Seoul National University, South Korea. Cho K S KS Lim J H JH Won D H DH Gye M C MC Chung K W KW Lee C C CC eng GENBANK AF142325 Journal Article

ENGLAND Insect Biochem Mol Biol 9207282 0 DNA, Complementary 0 Insect Proteins 0 Phosphoproteins 60-92-4 Cyclic AMP EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Amino Acid Sequence Animal Base Sequence Cattle Cyclic AMP Cyclic AMP-Dependent Protein Kinases metabolism DNA, Complementary Drosophila melanogaster genetics Female Insect Proteins genetics metabolism Male Molecular Sequence Data Phosphoproteins genetics metabolism Phosphorylation Sex Behavior, Animal Support, Non-U.S. Gov't FBrf0058608 93351855 8349114 1993 09 16 1993 09 16 2000 12 18

0016-6731 134 3 1993 Jul Compositional heterogeneity and patterns of molecular evolution in the Drosophila genome. 837-45 The rates and patterns of molecular evolution in many eukaryotic organisms have been shown to be influenced by the compartmentalization of their genomes into fractions of distinct base composition and mutational properties. We have examined the Drosophila genome to explore relationships between the nucleotide content of large chromosomal segments and the base composition and rate of evolution of genes within those segments. Direct determination of the G + C contents of yeast artificial chromosome clones containing inserts of Drosophila melanogaster DNA ranging from 140-340 kb revealed significant heterogeneity in base composition. The G + C content of the large segments studied ranged from 36.9% G + C for a clone containing the hunchback locus in polytene region 85, to 50.9% G + C for a clone that includes the rosy region in polytene region 87. Unlike other organisms, however, there was no significant correlation between the base composition of large chromosomal regions and the base composition at fourfold degenerate nucleotide sites of genes encompassed within those regions. Despite the situation seen in mammals, there was also no significant association between base composition and rate of nucleotide substitution. These results suggest that nucleotide sequence evolution in Drosophila differs from that of many vertebrates and does not reflect distinct mutational biases, as a function of base composition, in different genomic regions. Significant negative correlations between codon-usage bias and rates of synonymous site divergence, however, provide strong support for an argument that selection among alternative codons may be a major contributor to variability in evolutionary rates within Drosophila genomes. Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110. Carulli J P JP Krane D E DE Hartl D L DL Ochman H H eng EY07108 EY NEI GM-48407 GM NIGMS HG00750 HG NHGRI Journal Article

UNITED STATES Genetics 0374636 0 Codon IM Animal Base Composition Chromosomes, Fungal Codon Drosophila melanogaster genetics Evolution Gene Library Genome Sequence Analysis, DNA Support, U.S. Gov't, P.H.S. FBrf0158965 22608932 12723704 2003 05 01 2003 09 08

0016-6707 117 2-3 2003 Mar Structure, regulation and evolution of the crystal-Stellate system of Drosophila. 247-57 The crystal-Stellate system is one of the most known example of interaction between heterochromatin and euchromatin: a heterochromatic locus on the Y chromosome (crystal) 'represses' a euchromatic locus (Stellate) on the X chromosome in Drosophila melanogaster. The molecular mechanism regulating this interaction is not completely understood. It is becoming clear that an RNA interference (RNAi) mechanism could be responsible for the silencing carried out by crystal on the Stellate sequences. Here, a detailed structural analysis of all the sequences involved in the system is reported, demonstrating a their 'puzzling' structure. In addition three autosomal mutations: sting, scratch and sirio are described that interfere with the system. All of them are male sterile mutations and exhibit crystals made by the STELLATE protein in their primary spermatocytes. They are requested during oogenesis and early in embryogenesis as well. Hypothesis on the involvement of these genes in activating the Stellate sequences are discussed. Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università di Lecce, 73100 Lecce, Italy. Tritto Patrizia P Specchia Valeria V Fanti Laura L Berloco Maria M D'Alessandro Rosalba R Pimpinelli Sergio S Palumbo Gioacchino G Bozzetti Maria Pia MP eng Journal Article

Netherlands Genetica 0370740 0 Euchromatin 0 Heterochromatin 0 Repressor Proteins 0 SSL protein IM Amino Acid Sequence Animal Blotting, Northern Chromosome Mapping Drosophila melanogaster genetics Euchromatin Evolution, Molecular Gene Expression Regulation genetics Heterochromatin Molecular Sequence Data Mutation Repressor Proteins genetics Sequence Alignment FBrf0098855 97472944 9321417 1997 11 21 1997 11 21 2000 12 18

0022-2844 45 4 1997 Oct Synonymous substitution rates in Drosophila: mitochondrial versus nuclear genes. 378-91 Synonymous substitution rates in mitochondrial and nuclear genes of Drosophila were compared. To make accurate comparisons, we considered the following: (1) relative synonymous rates, which do not require divergence time estimates, should be used; (2) methods estimating divergence should take into account base composition; (3) only very closely related species should be used to avoid effects of saturation; (4) the heterogeneity of rates should be examined. We modified the methods estimating synonymous substitution numbers to account for base composition bias. By using these methods, we found that mitochondrial genes have 1.7-3.4 times higher synonymous substitution rates than the fastest nuclear genes or 4.5-9.0 times higher rates than the average nuclear genes. The average rate of synonymous transversions was 2.7 (estimated from the melanogaster species subgroup) or 2.9 (estimated from the obscura group) times higher in mitochondrial genes than in nuclear genes. Synonymous transversions in mitochondrial genes occurred at an approximately equivalent rate to those in the fastest nuclear genes. This last result is not consistent with the hypothesis that the difference in turnover rates between mitochondrial and nuclear genomes is the major factor determining higher synonymous substitution rates in mtDNA. We conclude that the difference in synonymous substitution rates is due to a combination of two factors: a higher transitional mutation rate in mtDNA and constraints on nuclear genes due to selection for codon usage. Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520-8106, USA. Moriyama E N EN Powell J R JR eng Journal Article

UNITED STATES J Mol Evol 0360051 0 DNA, Mitochondrial IM Animal Cell Nucleus genetics Comparative Study DNA, Mitochondrial genetics Drosophila genetics Drosophila melanogaster genetics Evolution, Molecular Genes, Insect Models, Genetic Mutation Support, U.S. Gov't, Non-P.H.S. Time Factors FBrf0130150 20501263 11046149 2000 12 19 2000 12 19

0270-7306 20 22 2000 Nov Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. 8536-47 Fragile X syndrome is the most common inherited form of mental retardation. It is caused by loss of FMR1 gene activity due to either lack of expression or expression of a mutant form of the protein. In mammals, FMR1 is a member of a small protein family that consists of FMR1, FXR1, and FXR2. All three members bind RNA and contain sequence motifs that are commonly found in RNA-binding proteins, including two KH domains and an RGG box. The FMR1/FXR proteins also contain a 60S ribosomal subunit interaction domain and a protein-protein interaction domain which mediates homomer and heteromer formation with each family member. Nevertheless, the specific molecular functions of FMR1/FXR proteins are unknown. Here we report the cloning and characterization of a Drosophila melanogaster homolog of the mammalian FMR1/FXR gene family. This first invertebrate homolog, termed dfmr1, has a high degree of amino acid sequence identity/similarity with the defined functional domains of the FMR1/FXR proteins. The dfmr1 product binds RNA and is similar in subcellular localization and embryonic expression pattern to the mammalian FMR1/FXR proteins. Overexpression of dfmr1 driven by the UAS-GAL4 system leads to apoptotic cell loss in all adult Drosophila tissues examined. This phenotype is dependent on the activity of the KH domains. The ability to induce a dominant phenotype by overexpressing dfmr1 opens the possibility of using genetic approaches in Drosophila to identify the pathways in which the FMR1/FXR proteins function. Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA. Wan L L Dockendorff T C TC Jongens T A TA Dreyfuss G G eng GENBANK AF305881 AF305882 Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Antibodies, Monoclonal 0 Insect Proteins 0 Nerve Tissue Proteins 139135-51-6 FMR-1 protein 63231-63-0 RNA IM Amino Acid Motifs Amino Acid Sequence Amino Acid Substitution Animal Antibodies, Monoclonal Apoptosis genetics Cloning, Molecular Drosophila melanogaster embryology genetics Embryo, Nonmammalian Gene Expression Regulation, Developmental Genes, Dominant Insect Proteins genetics immunology metabolism Molecular Sequence Data Nerve Tissue Proteins genetics immunology metabolism RNA metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0077016 95023174 7524034 1994 11 23 1994 11 23 2002 11 01

0305-1048 22 20 1994 Oct 11 Characterization of RNA binding specificity of the Drosophila sex-lethal protein by in vitro ligand selection. 4082-6 The Drosophila sex-lethal (Sxl) protein, a regulator of somatic sexual differentiation, is an RNA binding protein with two potential RNA recognition motifs (RRMs). It is thought to exert its function on splicing by binding to specific RNA sequences within Sxl and transformer (tra) pre-mRNAs. To examine the Sxl RNA binding specificity in detail, we performed in vitro selection and amplification of ligand RNAs from a random sequence pool on the basis of affinity with Sxl protein. After three cycles of selection and amplification, we cloned and sequenced 17 cDNAs corresponding to the RNAs selected in vitro. Sequencing showed that most of the RNAs selected contain polyuridine stretches surrounded by purine residues. In vitro binding analysis revealed that the sequences of the in vitro selected RNAs with relatively high affinity for Sxl show similarity to that of the Sxl- and tra-regulated acceptor regions, including the invariant AG sequence for splicing. These results suggest that Sxl recognizes and preferentially binds to a polyuridine stretch with a downstream AG sequence. Department of Biology, Faculty of Science, Kobe University, Japan. Sakashita E E Sakamoto H H eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 DNA, Complementary 0 Insect Hormones 0 Ligands 0 Sxl protein, Drosophila 27416-86-0 Poly U 63231-63-0 RNA IM Animal Base Sequence Binding Sites Cloning, Molecular DNA, Complementary chemistry genetics Drosophila melanogaster genetics Insect Hormones metabolism Ligands Molecular Sequence Data Poly U metabolism Polymerase Chain Reaction RNA metabolism RNA Splicing Sequence Analysis, RNA Support, Non-U.S. Gov't FBrf0149133 22038366 12021770 2002 06 03 2002 07 29 2002 11 05

1465-7392 4 6 2002 Jun Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. 439-44 Inhibitors of apoptosis (IAPs) inhibit caspases, thereby preventing proteolysis of apoptotic substrates. IAPs occlude the active sites of caspases to which they are bound and can function as ubiquitin ligases. IAPs are also reported to ubiquitinate themselves and caspases. Several proteins induce apoptosis, at least in part, by binding and inhibiting IAPs. Among these are the Drosophila melanogaster proteins Reaper (Rpr), Grim, and HID, and the mammalian proteins Smac/Diablo and Omi/HtrA2, all of which share a conserved amino-terminal IAP-binding motif. We report here that Rpr not only inhibits IAP function, but also greatly decreases IAP abundance. This decrease in IAP levels results from a combination of increased IAP degradation and a previously unrecognized ability of Rpr to repress total protein translation. Rpr-stimulated IAP degradation required both IAP ubiquitin ligase activity and an unblocked Rpr N terminus. In contrast, Rpr lacking a free N terminus still inhibited protein translation. As the abundance of short-lived proteins are severely affected after translational inhibition, the coordinated dampening of protein synthesis and the ubiquitin-mediated destruction of IAPs can effectively reduce IAP levels to lower the threshold for apoptosis. C370 LSRC, Research Drive, Box 3813, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Holley Christopher L CL Olson Michael R MR Colón-Ramos Daniel A DA Kornbluth Sally S eng GENBANK AF468029 GM61919 GM NIGMS Journal Article

England Nat Cell Biol 100890575 0 IAP-like protein, vertebrate 0 Peptides 0 Proteins 0 inhibitor of apoptosis protein 1, human 0 reaper peptide, Drosophila IM Animal Apoptosis physiology Cell Line Human Kidney cytology Molecular Sequence Data Oocytes cytology Peptides genetics metabolism Protein Binding physiology Proteins genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transfection Translation, Genetic physiology Xenopus laevis FBrf0158735 22615196 12729588 2003 05 05 2003 06 16

0006-291X 304 3 2003 May 9 Mitochondrial apoptotic pathways induced by Drosophila programmed cell death regulators. 531-7 Multicellular organisms eliminate unwanted or damaged cells by cell death, a process essential to the maintenance of tissue homeostasis. Cell death is a tightly regulated event, whose alteration by excess or defect is involved in the pathogenesis of many diseases such as cancer, autoimmune syndromes, and neurodegenerative processes. Studies in model organisms, especially in the nematode Caenorhabditis elegans, have been crucial in identifying the key molecules implicated in the regulation and execution of programmed cell death. In contrast, the study of cell death in Drosophila melanogaster, often an excellent model organism, has identified regulators and mechanisms not obviously conserved in other metazoans. Recent molecular and cellular analyses suggest, however, that the mechanisms of action of the main programmed cell death regulators in Drosophila include a canonical mitochondrial pathway. Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, E-28049 Madrid, Spain. Clavería Cristina C Torres Miguel M eng Journal Article Review Review, Tutorial

United States Biochem Biophys Res Commun 0372516 0 Drosophila Proteins 0 reaper peptide, Drosophila IM Amino Acid Sequence Animal Apoptosis Drosophila Proteins chemistry metabolism Drosophila melanogaster cytology metabolism Evolution Mitochondria metabolism Models, Biological Protein Structure, Tertiary Signal Transduction Support, Non-U.S. Gov't 66 FBrf0065527 94102032 8275850 1994 02 04 1994 02 04 2000 12 18

0950-1991 119 1 1993 Sep The role of the ovarian tumor locus in Drosophila melanogaster germ line sex determination. 123-34 The locus ovarian tumor (otu) is involved in several aspects of oogenesis in Drosophila melanogaster. The possible role of otu in the determination of the sexual identity of germ cells has not been extensively explored. Some otu alleles produce a phenotype known as ovarian tumors: ovarioles are filled with numerous poorly differentiated germ cells. We show that these mutant germ cells have a morphology similar to primary spermatocytes and that they express male germ line-specific reporter genes. This indicates that they are engaged along the male pathway of germ line differentiation. Consistent with this conclusion, we found that the splicing of Sex-lethal (Sxl) pre-mRNAs occurs in the male-specific mode in otu-transformed germ cells. The position of the otu locus in the regulatory cascade of germ line sex determination has been studied by using mutations that constitutively express the feminizing activity of the Sxl gene. The sexual transformation of the germ cells observed with several combinations of otu alleles can be reversed by constitutive expression of Sxl. This shows that otu acts upstream of Sxl in the process of germ line sex determination. Other phenotypes of otu mutations were not rescued by constitutive expression of Sxl, suggesting that several functions of otu are likely to be independent of sex determination. Finally, we show that the gene dosage of otu modifies the phenotype of ovaries heterozygous for the dominant alleles of ovo, another gene involved in germ line sex determination. One dose of otu+ enhances the ovoD ovarian phenotypes, while three doses partially suppress these phenotypes. Synergistic interaction between ovoD1 and otu alleles leads to the occasional transformation of chromosomally female germ cells into early spermatocytes. These interactions are similar to those observed between ovoD and one allele of the sans fille (snf) locus. Altogether, our results imply that the otu locus acts, along with ovo, snf, and Sxl, in a pathway (or parallel pathways) required for proper sex determination of the female germ line. Department of Genetics, Case Western Reserve University, Cleveland, OH 44106. Pauli D D Oliver B B Mahowald A P AP eng HD-17608 HD NICHD Journal Article

ENGLAND Development 8701744 IM otu ovo snf sxl Animal Drosophila melanogaster embryology genetics Female Gene Expression physiology Genes, Structural, Insect genetics Male Mutation genetics Oocytes pathology physiology Oogenesis genetics Ovarian Neoplasms genetics pathology Phenotype Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0148972 22065273 12070099 2002 06 18 2002 08 12 2002 10 21

0950-1991 129 13 2002 Jul Daughterless coordinates somatic cell proliferation, differentiation and germline cyst survival during follicle formation in Drosophila. 3255-67 During Drosophila oogenesis two distinct stem cell populations produce either germline cysts or the somatic cells that surround each cyst and separate each formed follicle. From analyzing daughterless (da) loss-of-function, overexpression and genetic interaction phenotypes, we have identified several specific requirements for da(+) in somatic cells during follicle formation. First, da is a critical regulator of somatic cell proliferation. Also, da is required for the complete differentiation of polar and stalk cells, and elevated da levels can even drive the convergence and extension that is characteristic of interfollicular stalks. Finally, da is a genetic regulator of an early checkpoint for germline cyst progression: Loss of da function inhibits normally occurring apoptosis of germline cysts at the region 2a/2b boundary of the germarium, while da overexpression leads to postmitotic cyst degradation. Collectively, these da functions govern the abundance and diversity of somatic cells as they coordinate with germline cysts to form functional follicles. Department of Biology, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904-4328, USA. Smith John E JE 3rd Cummings Craig A CA Cronmiller Claire C eng 5T32GM08136 GM NIGMS Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Insect Hormones 0 Nuclear Proteins 0 Transcription Factors 0 daughterless protein, Drosophila IM Animal Animals, Genetically Modified Apoptosis genetics Cell Differentiation Cell Division genetics DNA-Binding Proteins genetics metabolism Drosophila melanogaster genetics growth & development Female Gene Expression Regulation, Developmental Insect Hormones genetics metabolism Mutation Nuclear Proteins genetics metabolism Ovarian Follicle cytology growth & development Ovary cytology physiology Signal Transduction Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism FBrf0151925 22211538 12223408 2002 09 11 2002 11 08 2003 06 16

0950-1991 129 19 2002 Oct Heart tube patterning in Drosophila requires integration of axial and segmental information provided by the Bithorax Complex genes and hedgehog signaling. 4509-21 The Drosophila larval cardiac tube is composed of 104 cardiomyocytes that exhibit genetic and functional diversity. The tube is divided into the aorta and the heart proper that encompass the anterior and posterior parts of the tube, respectively. Differentiation into aorta and heart cardiomyocytes takes place during embryogenesis. We have observed living embryos to correlate morphological changes occurring during the late phases of cardiogenesis with the acquisition of organ function, including functional inlets, or ostiae. Cardiac cells diversity originates in response to two types of spatial information such that cells differentiate according to their position, both within a segment and along the anteroposterior axis. Axial patterning is controlled by homeotic genes of the Bithorax Complex (BXC) which are regionally expressed within the cardiac tube in non-overlapping domains. Ultrabithorax (Ubx) is expressed in the aorta whereas abdominal A (abd-A) is expressed in the heart, with the exception of the four most posterior cardiac cells which express Abdominal B (Abd-B). Ubx and abd-A functions are required to confer an aorta or a heart identity on cardiomyocytes, respectively. The anterior limit of the expression domain of Ubx, abd-A and Abd-B is independent of the function of the other genes. In contrast, abd-A represses Ubx expression in the heart and ectopic overexpression of abd-A transforms aorta cells into heart cardiomyocytes. Taken together, these results support the idea that BXC homeotic genes in the cardiac tube conform to the posterior prevalence rule. The cardiac tube is also segmentally patterned and each metamere contains six pairs of cardioblasts that are genetically diverse. We show that the transcription of seven up (svp), which is expressed in the two most posterior pairs of cardioblasts in each segment, is dependent on hedgehog (hh) signaling from the dorsal ectoderm. In combination with the axial information furnished by abd-A, the segmental hh-dependent information leads to the differentiation of the six pairs of svp-expressing cells into functional ostiae. Laboratoire de Génétique et Physiologie du Développement, UMR 6545 CNRS-Université, IBDM-CNRS-INSERM-Université de la Méditerranée, Campus de Luminy, Case 907, 13288 Marseille Cedex 09, France. Ponzielli Romina R Astier Martine M Chartier Aymeric A Gallet Armel A Thérond Pascal P Sémériva Michel M eng Journal Article

England Development 8701744 0 Abd-B proteins, Drosophila 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Homeodomain Proteins 0 Receptors, Steroid 0 seven-up protein, Drosophila 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Body Patterning Cleavage Stage, Ovum physiology DNA-Binding Proteins genetics metabolism physiology Drosophila Proteins genetics metabolism physiology Drosophila melanogaster embryology genetics metabolism Gene Expression Genes, Insect physiology Heart embryology Homeodomain Proteins genetics physiology Receptors, Steroid genetics metabolism Signal Transduction Support, Non-U.S. Gov't FBrf0108206 99242585 10224263 1999 07 12 1999 07 12 2003 06 16

0016-6731 152 1 1999 May stumps, a Drosophila gene required for fibroblast growth factor (FGF)-directed migrations of tracheal and mesodermal cells. 307-18 Fibroblast growth factors (FGFs) bind to FGF receptors, transmembrane tyrosine kinases that activate mitogenic, motogenic, and differentiative responses in different tissues. While there has been substantial progress in elucidating the Ras-MAP kinase pathway that mediates the differentiative responses, the signal transduction pathways that lead to directed cell migrations are not well defined. Here we describe a Drosophila gene called stumps that is required for FGF-dependent migrations of tracheal and mesodermal cells. These migrations are controlled by different FGF ligands and receptors, and they occur by different cellular mechanisms: the tracheal migrations occur as part of an epithelium whereas the mesodermal migrations are fibroblast-like. In the stumps mutant, tracheal cells fail to move out from the epithelial sacs, and only rudimentary tracheal branches form. Mesodermal cells fail in their dorsal migrations after gastrulation. The stumps mutation does not block all FGF signaling effects in these tissues: both random cell migrations and Ras-MAP kinase-mediated induction of FGF-specific effector genes occurred upon ectopic expression of the ligand or upon expression of a constitutively activated Ras protein in the migrating cells. The results suggest that stumps function promotes FGF-directed cell migrations, either by potentiating the FGF signaling process or by coupling the signal to the cellular machinery required for directed cell movement. Howard Hughes Medical Institute and Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305-5307, USA. Imam F F Sutherland D D Huang W W Krasnow M A MA eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 branchless protein, Drosophila 62031-54-3 Fibroblast Growth Factors EC 3.6.1.- ras Proteins IM Animal Cell Movement physiology Chromosome Mapping Dose-Response Relationship, Drug Drosophila melanogaster genetics Fibroblast Growth Factors genetics Gene Expression Regulation Immunohistochemistry Insect Proteins metabolism Mesoderm cytology physiology Models, Biological Phenotype Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trachea cytology physiology ras Proteins metabolism FBrf0151902 22318813 12431373 2002 11 14 2003 01 03 2003 05 12

1534-5807 3 5 2002 Nov Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation. 659-71 PAR-1 kinases are required to determine the anterior-posterior (A-P) axis in C. elegans and Drosophila, but little is known about their molecular function. We identified 14-3-3 proteins as Drosophila PAR-1 interactors and show that PAR-1 binds a domain of 14-3-3 distinct from the phosphoserine binding pocket. PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets. 14-3-3 mutants display identical phenotypes to par-1 mutants in oocyte determination and the polarization of the A-P axis. Together, these results indicate that PAR-1's function is mediated by the binding of 14-3-3 to its substrates. The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries. The Wellcome Trust/Cancer Research UK Institute and Department of Genetics, University of Cambridge, CB2 1QR, Cambridge, United Kingdom. Benton Richard R Palacios Isabel M IM St Johnston Daniel D eng Journal Article

United States Dev Cell 101120028 0 14-3-3 protein 0 Drosophila Proteins EC 1.14.16.2 Tyrosine 3-Monooxygenase EC 2.7.1.- PAR-1 protein EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Axis physiology Binding Sites Cell Polarity Drosophila Proteins genetics metabolism Drosophila melanogaster genetics metabolism physiology Female Germ Cells Oocytes metabolism Phosphorylation Protein-Serine-Threonine Kinases genetics metabolism Support, Non-U.S. Gov't Tyrosine 3-Monooxygenase chemistry genetics metabolism FBrf0134579 21098960 11171398 2001 02 22 2001 04 12 2002 11 08

0950-1991 128 5 2001 Mar An absolute requirement for Cubitus interruptus in Hedgehog signaling. 733-42 Hedgehog (Hh) proteins play diverse organizing roles in animal development by regulating gene expression in responding cells. Several components of the Hh signal transduction pathway have been identified, yet their precise role in mediating the various outputs of the pathway is still poorly understood. The Gli homolog Cubitus interruptus (Ci) is involved in controlling the transcription of Drosophila Hh target genes and thus represents the most downstream component known in this pathway. We address the question of whether the Hh pathway is distally branched or, in other words, whether the regulation of Ci activity is the sole output of Hh signaling. Putative Ci-independent branches of Hh signaling are explored by analyzing the behavior of cells that lack Ci but have undergone maximal activation of the Hh transduction pathway due to the removal of Patched (Ptc). The analysis of target gene expression and morphogenetic read-outs of Hh in embryonic, larval and adult stages indicates that Ci is absolutely required for all examined aspects of Hh outputs. We interpret this as evidence against the existence of Ci-independent branches in the Hh signal transduction pathway and propose that most cases of apparent Ci/Gli-independent Hh output can be attributed to the derepression of target gene expression in the absence of Ci/Gli repressor function. Institut für Molekularbiologie, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Méthot N N Basler K K eng Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 cubitus interruptus protein 0 dpp protein, Drosophila 0 engrail protein, Drosophila 0 patched protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Body Patterning Cell Adhesion DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics growth & development Female Gene Expression Regulation, Developmental Genes, Reporter Homeodomain Proteins genetics metabolism Insect Proteins genetics metabolism Membrane Proteins genetics metabolism Morphogenesis Mutation Proto-Oncogene Proteins genetics metabolism Signal Transduction Support, Non-U.S. Gov't Transcription Factors genetics metabolism Transgenes Wing anatomy & histology growth & development FBrf0058606 93351852 8349111 1993 09 16 1993 09 16 2002 11 01

0016-6731 134 3 1993 Jul The Drosophila sex determination gene snf is utilized for the establishment of the female-specific splicing pattern of Sex-lethal. 801-7 The Drosophila snf gene is a positive regulator of the sex determination gene Sex-lethal in both the germline and the soma. Its role in the soma is only evident when the probability of Sex-lethal activation has been reduced. For instance, in an otherwise wild-type background, females homozygous for a weak snf mutation produce both male and female progeny; however, when mated to males hemizygous for a null allele of Sex-lethal, they produce only male progeny. We demonstrate that the lack of female progeny is due to aberrant Sex-lethal regulation in late embryogenesis. In these mutant embryos, there is little accumulation of the late female-specific spliced RNAs and proteins. In contrast, in early embryogenesis, Sex-lethal regulation is not affected. The accumulation of both the early Sex-lethal transcripts and proteins is normal. These results suggest that the wild-type product of snf plays an important role in establishing the female-specific RNA splicing pattern of Sex-lethal. Whether snf influences the female-specific splice site choice directly or indirectly remains to be determined. Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106-4955. Albrecht E B EB Salz H K HK eng 5T32 GM08056 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Hormones 0 Sxl protein, Drosophila IM snf sxl Animal Drosophila melanogaster genetics Female Genes, Lethal Genes, Regulator Insect Hormones genetics Male Mutation RNA Splicing Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0151885 22233535 12297097 2002 09 25 2002 11 05

0012-1606 250 1 2002 Oct 1 Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations. 71-90 The tumor suppressor APC and its homologs, first identified for a role in colon cancer, negatively regulate Wnt signaling in both oncogenesis and normal development, and play Wnt-independent roles in cytoskeletal regulation. Both Drosophila and mammals have two APC family members. We further explored the functions of the Drosophila APCs using the larval brain as a model. We found that both proteins are expressed in the brain. APC2 has a highly dynamic, asymmetric localization through the larval neuroblast cell cycle relative to known mediators of embryonic neuroblast asymmetric divisions. Adherens junction proteins also are asymmetrically localized in neuroblasts. In addition they accumulate with APC2 and APC1 in nerves formed by axons of the progeny of each neuroblast-ganglion mother cell cluster. APC2 and APC1 localize to very different places when expressed in the larval brain: APC2 localizes to the cell cortex and APC1 to centrosomes and microtubules. Despite this, they play redundant roles in the brain; while each single mutant is normal, the zygotic double mutant has severely reduced numbers of larval neuroblasts. Our experiments suggest that this does not result from misregulation of Wg signaling, and thus may involve the cytoskeletal or adhesive roles of APC proteins. Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA. Akong Kathryn K McCartney Brooke M BM Peifer Mark M eng GM47857 GM NIGMS Journal Article

United States Dev Biol 0372762 0 Adenomatous Polyposis Coli Protein 0 Cytoskeletal Proteins 0 Drosophila Proteins 0 Tumor Suppressor Proteins 0 adenomatous polyposis coli protein 2 IM Adenomatous Polyposis Coli Protein Adherens Junctions Animal Body Patterning physiology Brain growth & development Cytoskeletal Proteins Drosophila Proteins metabolism Drosophila melanogaster Intracellular Fluid metabolism Larva Neurons Stem Cells Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Tumor Suppressor Proteins metabolism FBrf0136954 21297230 11404335 2001 06 13 2001 09 27

0016-6731 158 2 2001 Jun SSCP analysis of cDNA markers provides a dense linkage map of the Aedes aegypti genome. 715-26 An intensive linkage map of the yellow fever mosquito, Aedes aegypti, was constructed using single-strand conformation polymorphism (SSCP) analysis of cDNA markers to identify single nucleotide polymorphisms (SNPs). A total of 94 A. aegypti cDNAs were downloaded from GenBank and primers were designed to amplify fragments <500 bp in size. These primer pairs amplified 94 loci, 57 (61%) of which segregated in a single F(1) intercross family among 83 F(2) progeny. This allowed us to produce a dense linkage map of one marker every 2 cM distributed over a total length of 134 cM. Many A. aegypti cDNAs were highly similar to genes in the Drosophila melanogaster genome project. Comparative linkage analysis revealed areas of synteny between the two species. SNP polymorphisms are abundant in A. aegypti genes and should prove useful in both population genetics and mapping studies. Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA. Fulton R E RE Salasek M L ML DuTeau N M NM Black W C WC 4th eng AI 41436 AI NIAID AI 45430 AI NIAID Journal Article

United States Genetics 0374636 0 DNA, Complementary 0 Genetic Markers IM Aedes genetics Animal Base Sequence Chromosome Mapping Crosses, Genetic DNA, Complementary metabolism Expressed Sequence Tags Genetic Markers Genome Genotype Linkage (Genetics) Microsatellite Repeats Molecular Sequence Data Polymorphism, Single-Stranded Conformational Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0152006 22253747 12368261 2002 10 07 2002 11 05

0890-9369 16 19 2002 Oct 1 A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. 2497-508 Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. In Drosophila, the fly homolog of the FMR1 protein (dFMR1) binds to and represses the translation of an mRNA encoding of the microtuble-associated protein Futsch. We have isolated a dFMR1-associated complex that includes two ribosomal proteins, L5 and L11, along with 5S RNA. The dFMR1 complex also contains Argonaute2 (AGO2) and a Drosophila homolog of p68 RNA helicase (Dmp68). AGO2 is an essential component for the RNA-induced silencing complex (RISC), a sequence-specific nuclease complex that mediates RNA interference (RNAi) in Drosophila. We show that Dmp68 is also required for efficient RNAi. We further show that dFMR1 is associated with Dicer, another essential component of the RNAi pathway, and microRNAs (miRNAs) in vivo, suggesting that dFMR1 is part of the RNAi-related apparatus. Our findings suggest a model in which the RNAi and dFMR1-mediated translational control pathways intersect in Drosophila. Our findings also raise the possibility that defects in an RNAi-related machinery may cause human disease. Institute for Genome Research, Graduate School of Nutrition, University of Tokushima, Tokushima 770-8503, Japan. Ishizuka Akira A Siomi Mikiko C MC Siomi Haruhiko H eng Journal Article

United States Genes Dev 8711660 0 FMR1 protein, Drosophila 0 Insect Proteins 0 RNA, Ribosomal, 5S 0 RNA, Small Interfering 0 RNA-Binding Proteins 0 Recombinant Fusion Proteins 0 Ribosomal Proteins 0 protein p68 0 ribosomal protein L11 0 ribosomal protein L5 EC 2.7.1.37 Protein Kinases EC 2.7.7.- RNA Helicases IM Amino Acid Sequence Animal Cell Line Drosophila melanogaster Gene Silencing Human Insect Proteins genetics metabolism Molecular Sequence Data Protein Kinases genetics metabolism RNA Helicases genetics metabolism RNA, Ribosomal, 5S metabolism RNA, Small Interfering RNA-Binding Proteins genetics metabolism Recombinant Fusion Proteins genetics metabolism Ribosomal Proteins metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0155864 22453717 12551956 2003 02 04 2003 03 12

0021-9525 160 3 2003 Feb 3 Binding site for p120/delta-catenin is not required for Drosophila E-cadherin function in vivo. 313-9 Homophilic cell adhesion mediated by classical cadherins is important for many developmental processes. Proteins that interact with the cytoplasmic domain of cadherin, in particular the catenins, are thought to regulate the strength and possibly the dynamics of adhesion. beta-catenin links cadherin to the actin cytoskeleton via alpha-catenin. The role of p120/delta-catenin proteins in regulating cadherin function is less clear. Both beta-catenin and p120/delta-catenin are conserved in Drosophila. Here, we address the importance of cadherin-catenin interactions in vivo, using mutant variants of Drosophila epithelial cadherin (DE-cadherin) that are selectively defective in p120ctn (DE-cadherin-AAA) or beta-catenin-armadillo (DE-cadherin-Delta beta) interactions. We have analyzed the ability of these proteins to substitute for endogenous DE-cadherin activity in multiple cadherin-dependent processes during Drosophila development and oogenesis; epithelial integrity, follicle cell sorting, oocyte positioning, as well as the dynamic adhesion required for border cell migration. As expected, DE-cadherin-Delta beta did not substitute for DE-cadherin in these processes, although it retained some residual activity. Surprisingly, DE-cadherin-AAA was able to substitute for the wild-type protein in all contexts with no detectable perturbations. Thus, interaction with p120/delta-catenin does not appear to be required for DE-cadherin function in vivo. European Molecular Biology Laboratory, 69117 Heidelberg, Germany. Pacquelet Anne A Lin Li L Rorth Pernille P eng Journal Article 2003 01 27

United States J Cell Biol 0375356 0 Cadherins 0 Cell Adhesion Molecules 0 Cytoskeletal Proteins 0 Phosphoproteins 0 cadherin-associated Src substrate p120 0 delta-catenin IM Abnormalities genetics Animal Binding Sites genetics Body Patterning genetics CHO Cells Cadherins genetics metabolism Cell Adhesion genetics Cell Adhesion Molecules genetics metabolism Cell Aggregation genetics Cell Membrane metabolism ultrastructure Cell Movement physiology Cytoskeletal Proteins genetics metabolism Drosophila melanogaster cytology embryology metabolism Embryo, Nonmammalian cytology embryology metabolism Female Gene Expression Regulation, Developmental physiology Hamsters Male Models, Animal Mutation genetics Oogenesis physiology Phosphoproteins genetics metabolism Protein Structure, Tertiary genetics FBrf0138544 21424744 11533660 2001 09 04 2001 10 18 2002 07 09

1465-7392 3 9 2001 Sep Dual role of the fringe connection gene in both heparan sulphate and fringe-dependent signalling events. 809-15 The precise regulation of growth factor signalling is crucial to the molecular control of development in Drosophila. Post-translational modification of signalling molecules is one of the mechanisms that modulate developmental signalling specificity. We describe a new gene, fringe connection (frc), that encodes a nucleotide-sugar transporter that transfers UDP-glucuronic acid, UDP-N-acetylglucosamine and possibly UDP-xylose from the cytoplasm into the lumen of the endoplasmic reticulum/Golgi. Embryos with the frc mutation display defects in Wingless, Hedgehog and fibroblast growth factor signalling. Clonal analysis shows that fringe-dependent Notch signalling is disrupted in frc mutant tissue. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Selva E M EM Hong K K Baeg G H GH Beverley S M SM Turco S J SJ Perrimon N N Häcker U U eng AI31078 AI NIAID GM61110 GM NIGMS Journal Article

England Nat Cell Biol 100890575 2616-64-0 Uridine Diphosphate Glucuronic Acid 3616-06-6 Uridine Diphosphate Xylose 528-04-1 Uridine Diphosphate N-Acetylglucosamine 9050-30-0 Heparitin Sulfate EC 2.4 Glycosyltransferases EC 2.4.- fringe protein IM Nat Cell Biol. 2001 Oct;3(10):E229-31 11584283 Amino Acid Sequence Animal Cytoplasm metabolism Drosophila melanogaster embryology genetics growth & development Endoplasmic Reticulum metabolism Glycosyltransferases genetics metabolism Golgi Apparatus metabolism Heparitin Sulfate metabolism Human Molecular Sequence Data Morphogenesis Phenotype Sequence Alignment Sequence Homology, Amino Acid Signal Transduction physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Uridine Diphosphate Glucuronic Acid metabolism Uridine Diphosphate N-Acetylglucosamine metabolism Uridine Diphosphate Xylose metabolism Wing embryology growth & development FBrf0111415 99442382 10511556 1999 12 06 1999 12 06 2000 12 18

0016-6731 153 2 1999 Oct Genetic analysis of rolled, which encodes a Drosophila mitogen-activated protein kinase. 763-71 Genetic and molecular characterization of the dominant suppressors of D-raf(C110) on the second chromosome identified two gain-of-function alleles of rolled (rl), which encodes a mitogen-activated protein (MAP) kinase in Drosophila. One of the alleles, rl(Su23), was found to bear the same molecular lesion as rl(Sem), which has been reported to be dominant female sterile. However, rl(Su23) and the current stock of rl(Sem) showed only a weak dominant female sterility. Detailed analyses of the rl mutations demonstrated moderate dominant activities of these alleles in the Torso (Tor) signaling pathway, which explains the weak dominant female sterility observed in this study. The dominant rl mutations failed to suppress the terminal class maternal-effect mutations, suggesting that activation of Rl is essential, but not sufficient, for Tor signaling. Involvement of rl in cell proliferation was also demonstrated by clonal analysis. Branching and integration of signals in the MAP kinase cascade is discussed. Laboratory of Developmental Biology, Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan. Lim Y M YM Nishizawa K K Nishi Y Y Tsuda L L Inoue Y H YH Nishida Y Y eng Journal Article

UNITED STATES Genetics 0374636 EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 2.7.10.- ERK-A protein IM Amino Acid Sequence Animal Crosses, Genetic Drosophila melanogaster enzymology genetics Eye ultrastructure Female Genes, Dominant Heterozygote Homozygote Human Infertility, Female genetics Male Microscopy, Electron, Scanning Mitogen-Activated Protein Kinases chemistry genetics Molecular Sequence Data Mutation Proto-Oncogene Proteins c-raf genetics Rats Sequence Alignment Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Suppression, Genetic FBrf0082309 95262644 7538070 1995 06 14 1995 06 14 2001 10 18

0261-4189 14 9 1995 May 1 Localized Bicaudal-C RNA encodes a protein containing a KH domain, the RNA binding motif of FMR1. 2043-55 The Bicaudal-C (Bic-C) gene of Drosophila melanogaster is required for correct targeting of the migrating anterior follicle cells and for specifying anterior position. Females lacking any wild type copies of Bic-C produce only eggshells open at the anterior end, because of the failure of the columnar follicle cells to migrate in the correct position at the nurse cell--oocyte boundary. Embryos which develop from eggs produced in females with only one wild type copy of Bic-C show defects in anterior patterning and an abnormal persistence of oskar RNA in anterior regions. We cloned Bic-C and found that, in ovaries, Bic-C RNA is expressed only in germline cells. Bic-C RNA is localized to the oocyte in early oogenesis, and later concentrates at its anterior cortex. The Bic-C protein includes five KH domains similar to those found in the human fragile-X protein FMR1. Alteration of a highly conserved KH domain codon by mutation abrogates in vivo Bic-C function. These results suggest roles for the Bic-C protein in localizing RNAs and in intercellular signaling. Department of Biology, McGill University, Montréal, Québec, Canada. Mahone M M Saffman E E EE Lasko P F PF eng GENBANK U15928 Journal Article

ENGLAND EMBO J 8208664 0 Insect Hormones 0 Nerve Tissue Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 sycaudalD protein, Drosophila 139135-51-6 FMR-1 protein 63231-63-0 RNA 9007-49-2 DNA EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM EMBO J 1997 Jul 1;16(13):4152 Amino Acid Sequence Animal Base Sequence Cloning, Molecular Comparative Study DNA genetics Drosophila melanogaster embryology genetics metabolism Female Genes, Insect Human Insect Hormones genetics Male Molecular Sequence Data Nerve Tissue Proteins metabolism Oocytes metabolism Phenotype RNA genetics metabolism RNA Splicing RNA, Messenger genetics metabolism RNA-Binding Proteins genetics metabolism Receptor Protein-Tyrosine Kinases genetics Signal Transduction Support, Non-U.S. Gov't FBrf0094735 97349131 9205135 1997 07 23 1997 07 23 2002 11 01

0012-1606 186 2 1997 Jun 15 Genetic analysis of stomatogastric nervous system development in Drosophila using enhancer trap lines. 139-54 The stomatogastric nervous system (SNS) of Drosophila melanogaster is a small, simply organized neural circuitry which innervates the anterior enteric system. It is responsible for regulating the passage of food through the pharynx and esophagus and into the midgut. Here we show that the development of the SNS is amenable to genetic dissection. We screened lines from a P-element mutagenesis, selecting those with lacZ reporter gene expression and/or a phenotype in the SNS, associated glia, and garland cells. We report a collection of expression patterns and mutant phenotypes among lines found to have a mutation in genes required for the establishment of the larval SNS. Our results indicate that SNS development depends on pattern organizer genes including components of the Ras/Raf pathway. Max Planck Institut für biophysikalische Chemie, Abteilung für Molekulare Entwicklungsbiologie, Gottingen, Germany. Forjanic J P JP Chen C K CK Jäckle H H González Gaitán M M eng Journal Article

UNITED STATES Dev Biol 0372762 0 Adaptor Protein Complex alpha Subunits 0 Adaptor Proteins 0 Membrane Proteins EC 3.2.1.23 beta-Galactosidase IM Adaptor Protein Complex alpha Subunits Adaptor Proteins Amino Acid Sequence Animal Axons physiology Cell Movement Drosophila melanogaster embryology genetics growth & development Gastrointestinal System innervation Membrane Proteins chemistry genetics Molecular Sequence Data Mutation Nervous System embryology growth & development Support, Non-U.S. Gov't beta-Galactosidase genetics FBrf0102851 98267194 9601980 1999 01 05 1999 01 05 2001 11 02

0009-5915 107 2 1998 May Ultrastructure of regions containing homologous loci in polytene chromosomes of Drosophila melanogaster and Drosophila subobscura. 113-26 We have used a new approach involving in situ hybridisation and electron microscopy to establish ultrastructural homologies between polytene chromosome regions of Drosophila melanogaster and Drosophila subobscura. Twelve probes were chosen to cover all the chromosomal elements: the myospheroid gene, the collagen type IV gene, the collagen-like gene, the w26 homeobox gene, the beta3 tubulin gene, the kinesin heavy chain gene, the tryptophan hydrolase gene, the Hsp82, Hsp22-26 and Hsp23-28, Hsp68, Hsp70 genes and the beta unit of the F0-F1 ATPase gene. Most of these loci were previously undescribed in D. subobscura and imprecisely located in D. melanogaster. We have demonstrated here, by an ultrastructural analysis of each chromosomal region, that homologous genetic loci tend to show a similar ultrastructure in the two species. With a few exceptions, the structural homology extends to the chromosomal regions surrounding the loci. In some cases, however, no structurally recognisable homology can be seen either in the locus or in its flanking regions. Departament de Genética, Universitat de València, c/Dr. Moliner 50, E-46100-Burjassot, València, Spain. Ibo.Galindo@uv.es Cuenca J B JB Galindo M I MI Saura A O AO Sorsa V V de Frutos R R eng Journal Article

GERMANY Chromosoma 2985138R 0 DNA Probes 0 HSP26 protein 0 HSP30 protein 0 Heat-Shock Proteins 0 Heat-Shock Proteins 70 0 Integrins 0 Membrane Proteins 0 Tubulin 0 heat-shock protein 22 0 heat-shock protein 23 0 heat-shock protein 68 0 integrin PS, Drosophila 147096-66-0 heat-shock protein 82 9007-34-5 Collagen EC 1.14.16.4 Tryptophan Hydroxylase EC 3.6.1.- Kinesin EC 3.6.3.14 Proton-Translocating ATPases IM Animal Chromosome Banding Chromosomes ultrastructure Collagen genetics DNA Probes Drosophila melanogaster genetics ultrastructure Genes, Structural, Insect Heat-Shock Proteins genetics Heat-Shock Proteins 70 genetics Integrins genetics Kinesin genetics Membrane Proteins genetics Proton-Translocating ATPases genetics Sequence Homology, Nucleic Acid Tryptophan Hydroxylase genetics Tubulin genetics FBrf0055658 92404615 1525516 1992 10 22 1992 10 22 2000 12 18

0959-437X 2 4 1992 Aug Developmental regulation of the cell cycle. 614-20 The control of metazoan cell proliferation, a problem long the domain of cell culture studies, is now being examined in developing animals. Surprisingly, developmental regulation is mediated at a variety of cell-cycle stages. Highly conserved cell-cycle control mechanisms provide a focus for studying the regulatory processes involved. Department of Biochemistry, University of Adelaide, Australia. Saint R R Wigley P L PL eng Journal Article Review Review, Academic

ENGLAND Curr Opin Genet Dev 9111375 IM Animal Cell Cycle genetics physiology Drosophila melanogaster Embryo, Nonmammalian cytology growth & development Gene Expression Regulation physiology Support, Non-U.S. Gov't 56 FBrf0111993 20014924 10545462 1999 12 17 1999 12 17 2002 11 01

0016-6731 153 3 1999 Nov The genetic architecture of selection response. Inferences from fine-scale mapping of bristle number quantitative trait loci in Drosophila melanogaster. 1317-31 Quantitative trait loci (QTL) affecting responses and correlated responses to selection for abdominal and sternopleural bristle number have been mapped with high resolution to the X and third chromosomes. Advanced intercross recombinant isogenic chromosomes were constructed from high and low selection lines in an unselected inbred background, and QTL were detected using composite interval mapping and high density transposable element marker maps. We mapped a total of 26 bristle number QTL with large effects, which were in or immediately adjacent to intervals previously inferred to contain bristle number QTL on these chromosomes. The QTL contributing to response to selection for high bristle number were not the same as those contributing to response to selection for low bristle number, suggesting that distributions of allelic effects per locus may be asymmetrical. Correlated responses were more often attributable to loose linkage than pleiotropy or close linkage. Bristle number QTL mapping to the same locations have been inferred in studies with different parental strains. Of the 26 QTL, 20 mapped to locations consistent with candidate genes affecting peripheral nervous system development and/or bristle number. This facilitates determining the molecular basis of quantitative variation and allele frequencies by associating molecular variation at the candidate genes with phenotypic variation in bristle number in samples of alleles from nature. Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA. Nuzhdin S V SV Dilda C L CL Mackay T F TF eng GM-45146 GM NIGMS GM-45344 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Genetic Markers IM Alleles Animal Chromosome Mapping Crosses, Genetic Drosophila melanogaster anatomy & histology genetics Female Genetic Markers Male Quantitative Trait, Heritable Sense Organs anatomy & histology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0104540 98401146 9731193 1998 10 02 1998 10 02 2000 12 18

0006-291X 249 3 1998 Aug 28 Sampling the genomic pool of protein tyrosine kinase genes using the polymerase chain reaction with genomic DNA. 660-7 The polymerase chain reaction (PCR), with cDNA as template, has been widely used to identify members of protein families from many species. A major limitation of using cDNA in PCR is that detection of a family member is dependent on temporal and spatial patterns of gene expression. To circumvent this restriction, and in order to develop a technique that is broadly applicable we have tested the use of genomic DNA as PCR template to identify members of protein families in an expression-independent manner. This test involved amplification of DNA encoding protein tyrosine kinase (PTK) genes from the genomes of three animal species that are well known development models; namely, the mouse Mus musculus, the fruit fly Drosophila melanogaster, and the nematode worm Caenorhabditis elegans. Ten PTK genes were identified from the mouse, 13 from the fruit fly, and 13 from the nematode worm. Among these kinases were 13 members of the PTK family that had not been reported previously. Selected PTKs from this screen were shown to be expressed during development, demonstrating that the amplified fragments did not arise from pseudogenes. This approach will be useful for the identification of many novel members of gene families in organisms of agricultural, medical, developmental and evolutionary significance and for analysis of gene families from any species, or biological sample whose habitat precludes the isolation of mRNA. Furthermore, as a tool to hasten the discovery of members of gene families that are of particular interest, this method offers an opportunity to sample the genome for new members irrespective of their expression pattern. Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia. Oates A C AC Wollberg P P Achen M G MG Wilks A F AF eng Journal Article

UNITED STATES Biochem Biophys Res Commun 0372516 0 DNA Primers 9007-49-2 DNA EC 2.7.1.112 Protein-Tyrosine Kinase IM Amino Acid Sequence Animal Base Sequence Caenorhabditis elegans enzymology genetics growth & development Comparative Study DNA genetics DNA Primers genetics Drosophila melanogaster enzymology genetics growth & development Evolution, Molecular Gene Expression Regulation, Developmental Genes, Helminth Genes, Insect Genome Introns Mice Molecular Sequence Data Phylogeny Polymerase Chain Reaction Protein-Tyrosine Kinase genetics Pseudogenes Sequence Homology, Amino Acid Species Specificity Support, Non-U.S. Gov't FBrf0076147 95237016 7720588 1995 05 24 1995 05 24 2000 12 18

0950-1991 121 3 1995 Mar Serrate expression can functionally replace Delta activity during neuroblast segregation in the Drosophila embryo. 855-65 Serrate and Delta encode structurally related proteins in D. melanogaster that bind within a common extracellular region on the NOTCH receptor molecule. We used ectopic expression to determine if SERRATE could mediate in vivo functions parallel or antagonistic to those proposed for the putative NOTCH ligand DELTA. Our results demonstrate that Serrate can replace Delta gene function during embryonic neuroblast segregation and that expression of Serrate leads to a NOTCH-dependent suppression of achaete expression in proneural clusters. Our findings strongly suggest that SERRATE functions as an alternative ligand capable of NOTCH activation. Department of Biology, University of Rochester, NY 14627. Gu Y Y Hukriede N A NA Fleming R J RJ eng Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 Membrane Proteins 0 delta protein 0 notch protein 134324-36-0 Serrate protein IM N Ser Animal Drosophila melanogaster embryology Embryonic Induction genetics physiology Gene Expression Immunohistochemistry In Situ Hybridization Insect Hormones physiology Membrane Proteins genetics physiology Mutagenesis Nervous System embryology Support, Non-U.S. Gov't FBrf0042629 85286310 3928431 1985 10 16 1985 10 16 2000 12 18

0016-6731 111 1 1985 Sep Developmental genetics of the 2C-D region of the Drosophila X chromosome. 23-41 We have conducted a genetic and developmental analysis of genes within the 2C-D area of the X chromosome. Phenotypes of 33 mutations representing nine adjacent complementation groups including eight recessive lethals and one visible homeotic mutation (polyhomeotic) are described. Germline clonal analysis of the eight zygotic lethals has revealed three types of gene requirements: normal activity at two pupal lethal loci (corkscrew and C204) and one larval lethal locus (ultraspiracle) is required for normal embryogenesis; normal activity at three larval lethal loci (DF967, VE651 and Pgd) is required for normal oogenesis; and activity at only one locus (EA82), a larval lethal, appears to have no maternal requirement. Ambiguous results were obtained for the GF316 lethal complementation group. Analysis of mitotic figures of the pupal lethals indicates that C204 disrupts an essential mitotic function. This result correlates with the preblastoderm arrest observed among embryos derived from germline clones of C204. Embryos derived from germline clones of corkscrew (csw) exhibit a "twisted" phenotype. The recessive lethal ultraspiracle (usp) disrupts the organization of the posterior tip of the larval both zygotically and maternally: second instar usp/Y larvae derived from heterozygous usp/+ mothers possess an extra set of spiracles, whereas usp/Y embryos derived from females possessing a germline clone (usp/usp) exhibit a localized ventral defect in the ninth or posterior eighth abdominal segment. Analysis of the phenotypes of deficiency-hemizygous embryos indicates the presence of an embryonic zygotic lethal locus, as yet unidentified, which produces central nervous system and ventral hypoderm degeneration. Additional information on the genetic organization of loci within the adjacent 2E area are also described.(ABSTRACT TRUNCATED AT 250 WORDS) Perrimon N N Engstrom L L Mahowald A P AP eng HD17608 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Mapping Drosophila melanogaster genetics Female Genes, Lethal Linkage (Genetics) Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. X Chromosome FBrf0155857 22439804 12444081 2003 01 28 2003 04 03

0021-9258 278 5 2003 Jan 31 Biochemical function of female-lethal (2)D/Wilms' tumor suppressor-1-associated proteins in alternative pre-mRNA splicing. 3040-7 Genetic and molecular data have implicated the Drosophila gene female-lethal (2)d (fl (2)d) in alternative splicing regulation of genes involved in sexual determination. Sex-specific splicing is under the control of the female-specific regulatory protein sex-lethal (SXL). Co-immunoprecipitation and mass spectrometry results indicate that SXL and FL (2)D form a complex and that the protein VIRILIZER and a Ran-binding protein implicated in protein nuclear import are also present in complexes containing FL (2)D. A human homolog of FL (2)D was identified and cloned. Interestingly, this gene encodes a protein (WTAP) that was previously found to interact with the Wilms' tumor suppressor-1 (WT1), an isoform of which binds to and co-localizes with splicing factors. Alternative splicing of transformer pre-mRNA, a target of SXL regulation, was affected by immunodepletion of hFL (2)D/WTAP from HeLa nuclear extracts, thus arguing for a biochemical function of FL (2)D/WTAP proteins in splicing regulation. Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany. Ortega Angeles A Niksic Martina M Bachi Angela A Wilm Matthias M Sánchez Lucas L Hastie Nicholas N Valcárcel Juan J eng Journal Article 2002 11 19

United States J Biol Chem 2985121R 0 Drosophila Proteins 0 Nuclear Proteins 0 RNA Precursors 0 Recombinant Fusion Proteins 0 WT1 Proteins 0 female lethal(2)d protein IM Alternative Splicing Amino Acid Sequence Animal Cloning, Molecular Drosophila Proteins genetics Drosophila melanogaster genetics Human Kidney Neoplasms genetics Molecular Sequence Data Mutagenesis Nephroblastoma genetics Nuclear Proteins genetics RNA Precursors genetics Recombinant Fusion Proteins Support, Non-U.S. Gov't Templates, Genetic Transcription, Genetic WT1 Proteins metabolism FBrf0084080 96003633 7556096 1995 11 13 1995 11 13 2002 11 01

0261-4189 14 18 1995 Sep 15 Interaction of the sex-lethal RNA binding domains with RNA. 4530-9 Sex determination and X chromosome dosage compensation in Drosophila melanogaster are directed by the Sex-lethal (Sxl) protein. In part, Sxl functions by regulating the splicing of the transformer pre-mRNA by binding to a 3' splice site polypyrimidine tract. Polypyrimidine tracts are essential for splicing of metazoan pre-mRNAs. To unravel the mechanism of splicing regulation at polypyrimidine tracts we analyzed the interaction of Sxl with RNA. The RNA binding activity of Sxl was mapped to the two ribonucleoprotein consensus sequence domains of the protein. Quantitation of binding showed that both RNA binding domains (RBDs) were required in cis for site-specific RNA binding. Individual RBDs interacted with RNA more weakly and had lost the ability to discriminate between wild-type and mutant transformer polypyrimidine tracts. Structural elements in one of the RBDs that are likely to interact with a polypyrimidine tract were identified using nuclear magnetic resonance techniques. In addition, our data suggest that multiple imino protons of the transformer polypyrimidine tract were involved in hydrogen bonding. Interestingly, in vitro Sxl bound with equal affinity to polypyrimidine tracts of pre-mRNAs that it does not regulate in vivo. We discuss the implications of this finding for the mechanism through which Sxl may gain selectivity for particular polypyrimidine tracts in vivo. Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA. Kanaar R R Lee A L AL Rudner D Z DZ Wemmer D E DE Rio D C DC eng HD28063 HD NICHD Journal Article

ENGLAND EMBO J 8208664 0 Oligoribonucleotides 0 RNA-Binding Proteins 0 Recombinant Proteins 0 Sxl protein, Drosophila 63231-63-0 RNA IM Animal Base Sequence Binding Sites Drosophila melanogaster Magnetic Resonance Spectroscopy Molecular Sequence Data Nucleic Acid Conformation Oligoribonucleotides metabolism Protein Binding RNA metabolism RNA Splicing RNA-Binding Proteins genetics metabolism Recombinant Proteins metabolism Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0073424 94261583 8202491 1994 07 06 1994 07 06 2000 12 18

0027-8424 91 12 1994 Jun 7 Disulfide cross-linking in crude embryonic lysates reveals three complexes of the Drosophila morphogen dorsal and its inhibitor cactus. 5350-4 In Drosophila embryos dorsoventral polarity is determined by a concentration gradient of dorsal (dl) protein in the nuclei formed by the differential regulation of nuclear localization of dl protein. cactus (cact) represses the nuclear localization of dl protein. By introducing intermolecular disulfide bonds in homogenates of embryos, we detected three complexes of dl and/or cact proteins. Complex 1 (190 kDa) is a dl protein homodimer (dl2). Complex 2 (270 kDa) consists of one complex 1 and one cact molecule (dl2cact). Complex 3 (200 kDa) is a cact protein complex that does not contain dl protein. In wild-type embryos dl2cact was detected as the major form of dl protein, and dl2 was minor. With this assay virtually no dl monomer is detected. Analysis of the dl protein complexes in ventralized and dorsalized mutant embryos indicates that dl2cact is a cytoplasmic form, whereas dl2 is localized mainly in the nuclei. It seems that a small amount of dl2 is also present in the cytoplasm. Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany. Isoda K K Nüsslein-Volhard C C eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA-Binding Proteins 0 Disulfides 0 Macromolecular Systems 0 Nuclear Proteins 0 Phosphoproteins 0 dorsal protein, Drosophila 149059-01-8 cactus protein, Drosophila IM Animal Cell Compartmentation Cell Nucleus chemistry Cytoplasm chemistry DNA-Binding Proteins chemistry Disulfides Drosophila melanogaster embryology Macromolecular Systems Nuclear Proteins chemistry Phosphoproteins chemistry FBrf0091006 97158719 9006079 1997 02 24 1997 02 24 2000 12 18

0950-1991 124 1 1997 Jan The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the larval cuticle. 181-93 We report on the characterization of the first loss-of-function mutation in a Drosophila CREB gene, dCREB-A. In the epidermis, dCREB-A is required for patterning cuticular structures on both dorsal and ventral surfaces since dCREB-A mutant larvae have only lateral structures around the entire circumference of each segment. Based on results from epistasis tests with known dorsal/ventral patterning genes, we propose that dCREB-A encodes a transcription factor that functions near the end of both the DPP- and SPI-signaling cascades to translate the corresponding extracellular signals into changes in gene expression. The lateralizing phenotype of dCREB-A mutants reveals a much broader function for CREB proteins than previously thought. Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA. debbie_andrew@qmail.bs.jhu.edu Andrew D J DJ Baig A A Bhanot P P Smolik S M SM Henderson K D KD eng RO1 GM51311 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA Primers 0 DNA-Binding Protein, Cyclic AMP-Responsive 0 DNA-Binding Proteins 0 Trans-Activators 148412-93-5 dCREB-A protein IM Animal Chromosome Mapping DNA Primers DNA-Binding Protein, Cyclic AMP-Responsive biosynthesis genetics DNA-Binding Proteins biosynthesis genetics Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian physiology Embryonic Induction Enhancer Elements (Genetics) Genes, Insect Genetic Complementation Test Homozygote Larva Mutation Phenotype Polymerase Chain Reaction Salivary Glands cytology physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators biosynthesis genetics FBrf0080078 95137009 7835340 1995 02 27 1995 02 27 2001 11 02

0261-4189 14 2 1995 Jan 16 Characterization of rho GTPase family homologues in Drosophila melanogaster: overexpressing Rho1 in retinal cells causes a late developmental defect. 292-302 The rho family of GTPases has been implicated in regulating changes in cell morphology in response to extracellular signals. We have cloned three widely expressed members of this family from Drosophila melanogaster; a rho homologue (Rho1) and two rac homologues (Rac1 and Rac2). Flies harbouring a Rho1 transgene that is specifically expressed in the eye exhibit a dramatic dose dependent disruption of normal eye development. Flies bearing at least two copies of the transgene display a severe rough eye phenotype characterized by missing secondary and tertiary pigment cells, a substantial reduction in the number of photoreceptor cells and a grossly abnormal morphology of the rhabdomeres. Cell fate determination in the imaginal disc occurs normally and abnormalities become manifest late in pupariation, coincident with the phase when the cells undergo major morphological changes. This phenotype is modified by mutations at several other loci that have been implicated in signal transduction, but not by mutations in ras pathway components. MGH Cancer Center, Harvard Medical School, Charlestown, MA 02129. Hariharan I K IK Hu K Q KQ Asha H H Quintanilla A A Ezzell R M RM Settleman J J eng GENBANK L38309 L38310 L38311 Journal Article

ENGLAND EMBO J 8208664 0 DNA, Complementary 0 Fungal Proteins 107898-34-0 RHO1 protein EC 3.6.1.- GTP Phosphohydrolases EC 3.6.1.- GTP-Binding Proteins IM Amino Acid Sequence Animal Animals, Genetically Modified Base Sequence Cloning, Molecular DNA, Complementary Drosophila melanogaster embryology enzymology Fungal Proteins genetics physiology GTP Phosphohydrolases genetics physiology GTP-Binding Proteins genetics physiology Gene Expression Regulation, Developmental Human Microscopy, Electron, Scanning Molecular Sequence Data Phenotype Retina embryology enzymology ultrastructure Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0090577 97101733 8946251 1997 02 27 1997 02 27 2000 12 18

0214-6282 40 5 1996 Oct Cellular pathways acting along the germband and in the amnioserosa may participate in germband retraction of the Drosophila melanogaster embryo. 1043-51 Germband retraction in Drosophila melanogaster, like most embryonic morphogenetic events in this organism and in higher eukaryotes, is not well understood. We have taken several approaches to study the relationships between previously identified mutations (u-shaped, serpent, hindsight and tailup) that selectively cause germband retraction defects in homozygous embryos, and a more pleiotropically acting locus, DER/faint little ball. Our observations from genetic, immunohistochemical, and embryo culture experiments suggest that the former four loci are elements of at least two parallel and partially redundant cellular pathways that affect germband retraction by acting in amnioserosal development or maintenance. An additional discrete and unique pathway, represented by DER/faint little ball, is likely to function in the germband itself. While the role of the amnioserosa during germband retraction appears to be permissive, the action of DER in the germband may be mediated by the cytoskeleton. Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel. Goldman-Levi R R Miller C C Greenberg G G Gabai E E Zak N B NB eng Journal Article

SPAIN Int J Dev Biol 8917470 0 Receptors, Invertebrate Peptide 0 epidermal growth factor receptor homolog, Drosophila 22144-77-0 Cytochalasin D 64-86-8 Colchicine EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Colchicine pharmacology Cytochalasin D pharmacology Cytoskeleton metabolism Drosophila melanogaster embryology Immunohistochemistry Models, Genetic Morphogenesis physiology Mutation genetics Phenotype Receptor, Epidermal Growth Factor genetics metabolism Receptors, Invertebrate Peptide genetics metabolism Support, Non-U.S. Gov't FBrf0075969 94339181 8061051 1994 09 22 1994 09 22 2001 11 02

0006-3002 1223 1 1994 Aug 11 Suppression of heat-shock protein synthesis by short-chain fatty acids and alcohols. 23-8 We have shown that ethanol, propanol and butanol (at 0.5-2%) and salts of butyric and propionic acids (at 8-40 mM) all cause a major reduction in heat-shock protein (hsp) synthesis when present in the growth medium of Drosophila cultured cells (Kc and SL2) subjected to either increased temperature or chemical stressors. Inhibition of normal protein synthesis in unstressed cells was comparatively slight, and the usual suppression of synthesis of non-heat-shock proteins in stressed cells was unaffected. Maximum suppression of hsp synthesis occurred only if inhibitors were added before initiation of the stress response, an observation that eliminates the possibility that these findings are due to non-specific, toxic effects. Suppression was accompanied by severely reduced levels of both hsp70 mRNA and active heat-shock factor (HSF). We conclude that the inhibitors act by suppressing the initiation of transcription of heat-shock genes. Department of Anatomy, University of Birmingham Medical School, UK. Munks R J RJ Turner B M BM eng Journal Article

NETHERLANDS Biochim Biophys Acta 0217513 0 Alcohols 0 Fatty Acids, Volatile 0 Heat-Shock Proteins 0 Histones IM Alcohols pharmacology Animal Base Sequence Cells, Cultured Down-Regulation Drosophila melanogaster Fatty Acids, Volatile pharmacology Heat-Shock Proteins biosynthesis genetics Histones metabolism Molecular Sequence Data Support, Non-U.S. Gov't Transcription, Genetic FBrf0086682 97005549 8852848 1997 01 13 1997 01 13 2000 12 18

0016-6731 142 2 1996 Feb Molecular lesions associated with alleles of decapentaplegic identify residues necessary for TGF-beta/BMP cell signaling in Drosophila melanogaster. 493-505 We have identified the molecular lesions associated with six point mutations in the Drosophila TGF-beta homologue decapentaplegic (dpp). The sites of these mutations define residues within both the pro and ligand regions that are essential for dpp function in vivo. While all of these mutations affect residues that are highly conserved among TGF-beta superfamily members, the phenotypic consequences of the different alleles are quite distinct. Through an analysis of these mutant phenotypes, both in cuticle preparations and with molecular probes, we have assessed the functional significance of specific residues that are conserved among the different members of the superfamily. In addition, we have tested for conditional genetic interactions between the different alleles. We show that two of the alleles are temperature sensitive for the embryonic functions of dpp, such that these alleles are not only embryonic viable as homozygotes but also partially complement other dpp hypomorphs at low temperatures. Our results are discussed with regard to in vitro mutagenesis data on other TGF-beta-like molecules, as well as with regard to the regulation of dpp cell signaling in Drosophila. Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138, USA. kristi_wharton/brown.edu Wharton K K Ray R P RP Findley S D SD Duncan H E HE Gelbart W M WM eng Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Transforming Growth Factor beta 0 dpp protein, Drosophila IM Alleles Amino Acid Sequence Animal Drosophila melanogaster genetics Female Gene Expression Genetic Complementation Test Insect Proteins genetics Male Molecular Sequence Data Point Mutation Signal Transduction Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Temperature Transforming Growth Factor beta genetics FBrf0076034 95007768 7923366 1994 10 31 1994 10 31 2000 12 18

0092-8674 78 6 1994 Sep 23 Drosophila Jun mediates Ras-dependent photoreceptor determination. 973-86 The expression of the D. melanogaster transcription factor Jun in the eye imaginal disc correlates temporally and spatially with the determination of neuronal photoreceptor fate. Expression of dominant negative forms of Jun in photoreceptor precursor cells results in dose-dependent loss of photoreceptors in the adult fly. Conversely, localized overexpression of Jun in the eye imaginal disc can induce the differentiation of additional photoreceptor cells. Furthermore, the transformation of nonneuronal cone cells into R7 neurons elicited by constitutively active forms of sevenless, Ras1, Raf, and MAP kinase is relieved in the presence of Jun mutants. These results demonstrate a requirement of Jun downstream of the sevenless/ras signaling pathway for neuronal development in the Drosophila eye. European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany. Bohmann D D Ellis M C MC Staszewski L M LM Mlodzik M M eng Journal Article

UNITED STATES Cell 0413066 0 Eye Proteins 0 Membrane Glycoproteins 0 Proto-Oncogene Proteins 0 Proto-Oncogene Proteins c-jun 0 Recombinant Proteins 0 sevenless protein EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 3.6.1.- ras Proteins IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase metabolism Cell Differentiation Cones (Retina) physiology Drosophila melanogaster embryology Eye anatomy & histology embryology innervation Eye Proteins metabolism Genes, fos genetics Membrane Glycoproteins metabolism Models, Genetic Mutation Photoreceptors, Invertebrate anatomy & histology embryology Protein-Serine-Threonine Kinases metabolism Proto-Oncogene Proteins metabolism Proto-Oncogene Proteins c-jun genetics metabolism Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases metabolism Recombinant Proteins metabolism Suppression, Genetic Transformation, Genetic ras Proteins metabolism FBrf0135685 21246504 11348592 2001 05 11 2001 05 31

0092-8674 105 3 2001 May 4 Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. 357-68 Tuberous sclerosis complex is a dominant disorder that leads to the development of benign tumors in multiple organs. We have isolated a mutation in the Drosophila homolog of TSC1 (Tsc1). Cells mutant for Tsc1 are dramatically increased in size yet differentiate normally. Organ size is also increased in tissues that contain a majority of mutant cells. Clones of Tsc1 mutant cells in the imaginal discs undergo additional divisions but retain normal ploidy. We also show that the Tsc1 protein binds to Drosophila Tsc2 in vitro. Overexpression of Tsc1 or Tsc2 alone in the wing and eye has no effect, but co-overexpression leads to a decrease in cell size, cell number, and organ size. Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway. Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, CT 06536, USA. Potter C J CJ Huang H H Xu T T eng CA69408 CA NCI Journal Article

United States Cell 0413066 0 Proteins 0 Recombinant Fusion Proteins 0 Repressor Proteins 0 hamartin 11061-68-0 Insulin 169027-60-5 tuberous sclerosis 2 protein 9007-49-2 DNA IM Animal Cell Division physiology Cell Separation Cell Size physiology DNA metabolism Drosophila melanogaster cytology genetics physiology Electrophoresis, Polyacrylamide Gel Embryonic Structures anatomy & histology Epistasis, Genetic Female Flow Cytometry Genes, Reporter genetics Human Immunohistochemistry Insulin metabolism Male Mosaicism Photoreceptors, Invertebrate cytology physiology ultrastructure Proteins genetics metabolism Recombinant Fusion Proteins genetics metabolism Repressor Proteins genetics metabolism Signal Transduction genetics physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tuberous Sclerosis genetics Wing anatomy & histology physiology FBrf0125245 20123694 10660298 2000 03 20 2000 03 20 2003 06 16

0960-9822 10 1 2000 Jan 13 Cactus-independent regulation of Dorsal nuclear import by the ventral signal. 23-6 Rel-family transcription factors function in a variety of biological processes, including development and immunity. During early Drosophila development, the Toll-Cactus-Dorsal pathway regulates the establishment of the embryonic dorsoventral axis. The last step in this pathway is the graded nuclear import of the Rel protein Dorsal. Dorsal is retained in the cytoplasm by the IkappaB-family protein Cactus. Phosphorylation of both Dorsal and Cactus is regulated by a Toll-receptor-dependent ventral signal relayed by the Tube and Pelle proteins. Phosphorylation of Cactus leads to its degradation and to the release of Dorsal to form a ventral-to-dorsal nuclear Dorsal gradient. To understand how the ventral signal regulates the nuclear import and activity of Dorsal, we deleted its conserved nuclear localization signal (NLS). The truncated protein remained in the cytoplasm and could antagonize the function of wild-type Dorsal, suggesting that Dorsal forms a dimer in the cytoplasm. Further, the nuclear import of a mutant Dorsal protein that failed to interact with Cactus was still regulated by the ventral signal. Our results are consistent with a model in which ventral signal-dependent modification of both Cactus and Dorsal is required for the graded nuclear import of Dorsal. Waksman Institute, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854-8020, USA. Drier E A EA Govind S S Steward R R eng Journal Article

ENGLAND Curr Biol 9107782 0 DNA-Binding Proteins 0 Insect Proteins 0 Membrane Glycoproteins 0 Nuclear Proteins 0 Phosphoproteins 0 dorsal protein, Drosophila 0 tube protein, Drosophila 118929-01-4 Toll protein, Drosophila 149059-01-8 cactus protein, Drosophila EC 2.7.1.- pelle protein EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Animals, Genetically Modified DNA-Binding Proteins genetics physiology Dimerization Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology ultrastructure Insect Proteins genetics physiology Membrane Glycoproteins genetics physiology Morphogenesis genetics Nuclear Proteins genetics physiology Phenotype Phosphoproteins genetics physiology Phosphorylation Protein Processing, Post-Translational Protein-Serine-Threonine Kinases genetics physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0084541 96017651 7588073 1995 11 30 1995 11 30 2000 12 18

0950-1991 121 10 1995 Oct Ventral veinless, the gene encoding the Cf1a transcription factor, links positional information and cell differentiation during embryonic and imaginal development in Drosophila melanogaster. 3405-16 The ventral veinless gene (vvl) encodes the previously identified Cf1a protein, a transcription factor containing a POU-domain. During embryonic development vvl function is required for the formation of the tracheal tree and in the patterning of the ventral ectoderm. During imaginal development vvl is required for cell proliferation and the differentiation of the wing veins. vvl expression is restricted to the regions where its function is required, and is dependent on the coordinate activities of signalling molecules such as decapentaplegic, wingless and hedgehog. vvl interacts with other genes involved in vein differentiation, including veinlet, thick veins, torpedo, decapentaplegic and Notch suggesting that vvl function may affect several cell-to-cell communication pathways. We propose that the gene vvl integrates information from different signalling molecules and regulates the expression of specific cell differentiation genes during tracheal development and vein differentiation. Department of Genetics, University of Cambridge, UK. de Celis J F JF Llimargas M M Casanova J J eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Transcription Factors 0 dfr protein IM Animal Cell Differentiation genetics Cell Division genetics DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Ectoderm physiology Gene Expression Regulation, Developmental Genes, Insect Morphogenesis genetics Signal Transduction genetics Support, Non-U.S. Gov't Trachea embryology Transcription Factors genetics FBrf0051839 90249726 2110920 1990 06 20 1990 06 20 2000 12 18

0890-9369 4 2 1990 Feb rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. 190-203 rhomboid (rho) belongs to a group of four genes involved in the elaboration of positional information at a ventrolateral level in the Drosophila embryo. Mutations at any of these four loci also lead to a variety of other phenotypes, including reduction in the number of stretch receptor organs (chordotonal organs) in the peripheral nervous system (PNS). We have cloned rho with the aid of a lacZ-bearing P-element inserted into the rho gene. In the early blastoderm stage, a putative rho transcript is expressed in ventrolateral strips corresponding to the domain of activity of the rho gene on the embryonic fate map. Later expression of the transcript correlates with regions of the embryo that are disrupted in rho mutants and includes a cell that may be the precursor for the missing stretch receptor organs. We hypothesize that rho acts very early in differentiation pathways to specify the identities of domains and isolated precursor cells. Sequence analysis suggests that this transcript codes for a trans-membrane protein. Howard Hughes Medical Institute, University of California, San Francisco 94143. Bier E E Jan L Y LY Jan Y N YN eng Journal Article

UNITED STATES Genes Dev 8711660 9007-49-2 DNA IM Genes Dev 1990 Apr;4(4):680-1 Amino Acid Sequence Animal Base Sequence DNA genetics Drosophila melanogaster embryology genetics Gene Expression Lac Operon Molecular Sequence Data Muscles embryology Mutation Peripheral Nerves embryology Phenotype Support, Non-U.S. Gov't FBrf0076541 95095044 8001784 1995 01 23 1995 01 23 2000 12 18

0016-6731 138 1 1994 Sep The thick veins gene of Drosophila is required for dorsoventral polarity of the embryo. 165-78 We have discovered a new member of the class of genes controlling embryonic dorsoventral patterning. Mutants of the thick veins (tkv) gene have been described previously (as slater alleles) as embryonic lethal, lacking dorsal epidermis, but not as showing a recognizable dorsoventral phenotype. We show here that maternal alteration of function coupled with zygotic reduction of function of tkv is strongly ventralizing. In addition, in double heterozygous combinations in the mother, tkv mutations increase the ventralizing effect of dominant, weakly ventralizing alleles of the maternal effect, dorsoventral genes easter and cactus. An interaction is also seen with zygotic dorsoventral genes: tkv interacts maternally and zygotically in double heterozygotes with decapentaplegic and zygotically with screw in double homozygotes. We conclude that both maternally and zygotically supplied wild-type tkv product can play a role in dorsoventral patterning of the early embryo. On the basis of the phenotype of trans-heterozygous adult escapers, we propose that tkv might act by potentiating the activity of the zygotically acting decapentaplegic gene. Centre de Génétique Moléculaire CNRS, Gif sur Yvette, France. Terracol R R Lengyel J A JA eng Journal Article

UNITED STATES Genetics 0374636 IM dpp scw tkv Alleles Animal Drosophila melanogaster embryology genetics Female Genes, Insect Genes, Lethal Genetic Complementation Test Heterozygote Homozygote Male Models, Genetic Mutation Phenotype Support, Non-U.S. Gov't Wing blood supply embryology FBrf0155501 22429080 12540903 2003 01 23 2003 03 07

0028-0836 421 6921 2003 Jan 23 A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity. 379-84 The PAR-4 and PAR-1 kinases are necessary for the formation of the anterior-posterior (A-P) axis in Caenorhabditis elegans. PAR-1 is also required for A-P axis determination in Drosophila. Here we show that the Drosophila par-4 homologue, lkb1, is required for the early A-P polarity of the oocyte, and for the repolarization of the oocyte cytoskeleton that defines the embryonic A-P axis. LKB1 is phosphorylated by PAR-1 in vitro, and overexpression of LKB1 partially rescues the par-1 phenotype. These two kinases therefore function in a conserved pathway for axis formation in flies and worms. lkb1 mutant clones also disrupt apical-basal epithelial polarity, suggesting a general role in cell polarization. The human homologue, LKB1, is mutated in Peutz-Jeghers syndrome and is regulated by prenylation and by phosphorylation by protein kinase A. We show that protein kinase A phosphorylates Drosophila LKB1 on a conserved site that is important for its activity. Thus, Drosophila and human LKB1 may be functional homologues, suggesting that loss of cell polarity may contribute to tumour formation in individuals with Peutz-Jeghers syndrome. The Wellcome Trust/Cancer Research UK. Martin Sophie G SG St Johnston Daniel D eng GENBANK AY069241 Journal Article

England Nature 0410462 0 Drosophila Proteins 0 RNA, Messenger 573-58-0 Congo Red EC 2.7.1.- LKB1 protein EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Amino Acid Sequence Animal Body Patterning Cell Polarity Congo Red Conserved Sequence Cyclic AMP-Dependent Protein Kinases metabolism Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster cytology embryology enzymology genetics Epithelial Cells cytology Genes, Insect genetics Human Molecular Sequence Data Peutz-Jeghers Syndrome enzymology Phosphorylation Protein Transport Protein-Serine-Threonine Kinases chemistry genetics metabolism RNA, Messenger genetics metabolism Support, Non-U.S. Gov't FBrf0037190 82081830 6118854 1982 02 12 1982 02 12 2000 12 18

0305-1048 9 19 1981 Oct 10 Two closely linked transcription units within the 63B heat shock puff locus of D. melanogaster display strikingly different regulation. 5075-92 We report the isolation and characterization of a cloned DNA of D. melanogaster, Dm4L, that is derived from the major heat shock puff site at 63B. This segment contains two closely linked genes that are each present once per Drosophila haploid genome. One of these, the hsp 83 gene, encodes an abundant heat shock mRNA that, unlike other major heat shock mRNAs, is also abundant in uninduced (23 degrees) kco cells. Although only a slight increase in the level of total hsp 83 RNA can be detected after heat shock in Kco cells, the level of hsp 83 poly(A)+ mRNA increases more than 6-fold and the level of pulse-labeled hsp 83 RNA in total cellular RNA increases 11-fold relative to uninduced cells. In contrast, the levels of total, poly(A)+, and pulse-labeled RNA homologous to the second gene, 63B-T2, are approximately the same in both induced and uninduced cells. Hence, even though these genes are separated by only one thousand base pairs, and, from in situ hybridization to polytene chromosomes, both lie within the heat shock puff, they display strikingly different regulatory properties, These results demonstrate that close linkage of a gene to a heat shock puff is not sufficient to render its expression heat inducible. O'Connor D D Lis J T JT eng GM25232 GM NIGMS Journal Article

ENGLAND Nucleic Acids Res 0411011 0 DNA, Recombinant 0 Heat-Shock Proteins 0 Proteins 0 RNA, Messenger 24937-83-5 Poly A IM Animal Cloning, Molecular DNA, Recombinant isolation & purification Drosophila melanogaster Gene Expression Regulation Heat Heat-Shock Proteins Microscopy, Electron Nucleic Acid Hybridization Poly A metabolism Proteins genetics RNA, Messenger metabolism Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0047217 87204224 3106978 1987 06 09 1987 06 09 2000 12 18

0027-8424 84 9 1987 May Cloning and characterization of a dispersed, multicopy, X chromosome sequence in Drosophila melanogaster. 2843-7 We have isolated and characterized a dispersed middle repetitive DNA sequence from Drosophila melanogaster that is concentrated on the euchromatic portion of the X chromosome. In situ hybridization of the repeat unit to salivary gland chromosomes shows the sequence is distributed among approximately 10 major and 20 minor X chromosomal sites. Based on DNA sequence analysis of homologous sequences from three different cytogenetic regions, the 372-base-pair repeat unit appears to be (A + T)-rich and noncoding and shows strong sequence conservation among units from different chromosomal regions. The nature and distribution of this sequence are suggestive of the hypothetical X chromosome DNA sequences thought to be involved in the primary establishment of sex determination and dosage compensation in Drosophila. Waring G L GL Pollack J C JC eng HD00524 HD NICHD Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 IM Animal Base Sequence Cloning, Molecular Comparative Study Drosophila melanogaster genetics Nucleic Acid Hybridization Sequence Homology, Nucleic Acid Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. X Chromosome FBrf0135876 21184115 11287191 2001 04 05 2001 08 16

0925-4773 102 1-2 2001 Apr Distinct domains mediate the early and late functions of the Drosophila ovarian tumor proteins. 181-91 The Drosophila melanogaster ovarian tumor (otu) gene encodes two novel protein isoforms that are required at multiple stages of oogenesis. We have examined the activity of a set of C-terminal truncation Otu proteins as well as a GFP-tagged Otu (Otu-GFP). These experiments have shown that a putative Tudor domain in the central region of the large Otu isoform and a separate domain in the C-terminal region are required for regulation of cyst formation and oocyte maturation, respectively. We also present evidence that a portion of Otu co-fractionates with mRNA/protein complexes (mRNPs) and show that Otu-GFP associates with cytoplasmic aggregates at periphery of the nucleus at an intermediate stage of oogenesis. This study substantially clarifies the relationship between Otu structure and function and reveals new clues about interacting components. Department of Biology, CB# 3280, University of North Carolina at Chapel Hill, 27599-3280, USA. Glenn L E LE Searles L L LL eng GM52830 GM NIGMS Journal Article

Ireland Mech Dev 9101218 0 Insect Proteins 0 Luminescent Proteins 0 Protein Isoforms 0 RNA, Messenger 0 Recombinant Fusion Proteins 0 ovarian tumor protein, Drosophila 147336-22-9 green fluorescent protein IM Animal Blotting, Western Cell Nucleus metabolism Drosophila melanogaster embryology Female Insect Proteins chemistry genetics Luminescent Proteins metabolism Microscopy, Confocal Models, Genetic Mutation Oocytes metabolism Ovary cytology embryology metabolism Protein Isoforms Protein Structure, Tertiary RNA, Messenger metabolism Recombinant Fusion Proteins metabolism Structure-Activity Relationship Subcellular Fractions metabolism Support, U.S. Gov't, P.H.S. Transgenes FBrf0151438 22092621 12097909 2002 07 04 2002 07 30 2002 11 01

0028-0836 418 6893 2002 Jul 4 A host parasite interaction rescues Drosophila oogenesis defects. 76-9 The cytoplasmically inherited bacterium Wolbachia pipientis is a widespread parasite of arthropods that manipulates the reproductive biology of its hosts, often to their detriment, in order to foster its own transmission through egg cytoplasm. Here we report that infection by Wolbachia restores fertility to Drosophila melanogaster mutant females prevented from making eggs by protein-coding lesions in Sex-lethal (Sxl), the master regulator of sex determination. Suppression of sterility by Wolbachia discriminates markedly among similar germline-specific Sxl alleles, and is not observed for mutations in other genes that produce similar 'tumorous ovary' phenotypes, including one that blocks Sxl germline expression. This allele and gene specificity indicates that suppression probably results from a specific interaction with Sxl protein, rather than from a bypass of the normal germline requirement for this developmental regulator or from an effect on Sxl expression. The Sxl-Wolbachia interaction provides a rare opportunity to explore host-parasite relationships at the molecular level in a model insect. Furthermore, demonstration that a parasite infection can counteract the deleterious effects of mutations in host genes illustrates how hosts might become dependent on parasites. Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, California 94720-3204, USA. Starr Diana J DJ Cline Thomas W TW eng Journal Article

England Nature 0410462 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Alleles Animal Drosophila melanogaster cytology genetics microbiology physiology Embryo Loss genetics Female Gene Expression Genes, Lethal genetics Germ-Line Mutation genetics Host-Parasite Relations physiology Infertility, Female genetics Linkage (Genetics) genetics Male Oogenesis genetics physiology Ovary abnormalities cytology physiology Phenotype RNA-Binding Proteins genetics physiology Sex Characteristics Sex Determination (Genetics) Wolbachia physiology X Chromosome genetics FBrf0129898 20504797 11050330 2000 11 21 2000 11 21 2002 04 19

0168-9525 16 10 2000 Oct Genes that fight infection: what the Drosophila genome says about animal immunity. 442-9 From deciphering the principles of heredity to identifying the genes that control development, the fruit fly Drosophila melanogaster is being used to deconstruct an increasing number of biological processes. Genetic studies of Drosophila responses to microbial infection have identified regulators of innate immunity that are functionally conserved in mammals. These recent findings highlight the ancient origins of animal immune responses and demonstrate the potential of Drosophila for dissecting host-pathogen interactions. The sequencing of the Drosophila genome both enhances genetic approaches and provides new clues for the identification of key components of innate immunity. This article summarizes how information gained from genomic analysis contributes to our understanding of how animals cope with infectious disease. Centre de Génétique Moléculaire, CNRS, 91198, Gif-sur-Yvette, France. Khush R S RS Lemaitre B B eng Journal Article Review Review, Tutorial

ENGLAND Trends Genet 8507085 0 Bacterial Proteins 0 Cytokines 0 Insect Proteins 0 Membrane Glycoproteins 0 NF-kappa B 118929-01-4 Toll protein, Drosophila EC 3.4.- Endopeptidases IM Adaptation, Physiological genetics Animal Animals genetics immunology Bacterial Infections immunology Bacterial Proteins chemistry immunology Chromosome Mapping Cytokines physiology Drosophila melanogaster genetics immunology Endopeptidases physiology Evolution, Molecular Gene Expression Regulation Immunity genetics Insect Proteins genetics physiology Membrane Glycoproteins genetics physiology NF-kappa B physiology Phagocytosis Protein Structure, Tertiary Signal Transduction Support, Non-U.S. Gov't 73 FBrf0099245 97474313 9335337 1997 11 03 1997 11 03 2000 12 18

0092-8674 91 1 1997 Oct 3 Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins. 85-97 The approximately 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. Hall T M TM Porter J A JA Young K E KE Koonin E V EV Beachy P A PA Leahy D J DJ eng PDB 1AT0 1AT0SF Journal Article

UNITED STATES Cell 0413066 0 Insect Proteins 0 Peptide Fragments 0 Proteins 149291-21-4 hedgehog protein, Drosophila IM Amino Acid Sequence Animal Binding Sites Crystallography, X-Ray Drosophila melanogaster chemistry genetics Insect Proteins chemistry genetics Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Peptide Fragments chemistry Protein Splicing physiology Protein Structure, Secondary Proteins genetics metabolism Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0160742 22668876 12783785 2003 06 04 2003 08 14

0950-1991 130 14 2003 Jul Splits ends is a tissue/promoter specific regulator of Wingless signaling. 3125-35 Wingless directs many developmental processes in Drosophila by regulating expression of specific target genes through a conserved signaling pathway. Although many nuclear factors have been implicated in mediating Wingless-induced transcription, the mechanism of how Wingless regulates different targets in different tissues remains poorly understood. We report here that the split ends gene is required for Wingless signaling in the eye, wing and leg imaginal discs. Expression of a dominant-negative version of split ends resulted in more dramatic reductions in Wingless signaling than split ends-null alleles, suggesting that it may have a redundant partner. However, removal of split ends or expression of the dominant-negative had no effect on several Wingless signaling readouts in the embryo. The expression pattern of Split ends cannot explain this tissue-specific requirement, as the protein is predominantly nuclear and present throughout embryogenesis and larval tissues. Consistent with its nuclear location, the split ends dominant-negative acts downstream of Armadillo stabilization. Our data indicate that Split ends is an important positive regulator of Wingless signaling in larval tissues. However, it has no detectable role in the embryonic Wingless pathway, suggesting that it is a tissue or promoter-specific factor. Department of Molecular, Cellular and Developmental Biology, University of Michigan, Natural Science Building, Ann Arbor, MI 48109, USA. Lin Hua V HV Doroquez David B DB Cho Soochin S Chen Fangli F Rebay Ilaria I Cadigan Ken M KM eng R01 GM59846 GM NIGMS Journal Article

England Development 8701744 0 Drosophila Proteins 0 Homeodomain Proteins 0 Nuclear Proteins 0 Proto-Oncogene Proteins 0 Spen protein 117758-26-6 wingless protein, Drosophila IM Alleles Animal Cell Nucleus metabolism Drosophila Proteins biosynthesis genetics Drosophila melanogaster Genes, Dominant Homeodomain Proteins genetics physiology Microscopy, Electron, Scanning Microscopy, Fluorescence Mutation Nuclear Proteins genetics physiology Phenotype Photoreceptors, Invertebrate pathology ultrastructure Promoter Regions (Genetics) Proto-Oncogene Proteins biosynthesis genetics Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0144881 21683412 11825879 2002 02 04 2002 02 28 2003 06 16

0890-9369 16 3 2002 Feb 1 mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family. 388-98 The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development. Receptors for the pathway have yet to be identified. Here we have identified a Drosophila gene that shows embryonic mutant phenotypes identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e mutations. We named this gene master of marelle (mom). Genetic analyses place mom's function between upd (the ligand) and hop. We further show that cultured cells transfected with the mom gene bind UPD and activate the HOP/STAT92E signal transduction pathway. mom encodes a protein distantly related to the mammalian cytokine receptor family. These data show that mom functions as a receptor of the Drosophila JAK/STAT signal transduction pathway. The Laboratory of Immunobiology, National Institutes of Health, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Chen Hua-Wei HW Chen Xiu X Oh Su-Wan SW Marinissen Maria J MJ Gutkind J Silvio JS Hou Steven X SX eng Journal Article

United States Genes Dev 8711660 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Glycoproteins 0 Insect Proteins 0 Membrane Proteins 0 Porc protein 0 Receptors, Cytokine 0 STAT92E protein 0 Trans-Activators 0 outstretched protein, Drosophila EC 2.7.1.- Hop protein EC 2.7.1.- Janus kinase 1 EC 2.7.1.112 Protein-Tyrosine Kinase IM Amino Acid Sequence Animal Body Patterning Cells, Cultured Cloning, Molecular DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology growth & development physiology Exons Female Glycoproteins genetics metabolism In Situ Hybridization Insect Proteins genetics metabolism Introns Membrane Proteins genetics metabolism Molecular Sequence Data Protein-Tyrosine Kinase genetics metabolism Receptors, Cytokine genetics metabolism Signal Transduction physiology Support, U.S. Gov't, Non-P.H.S. Trachea metabolism Trans-Activators genetics metabolism Transfection FBrf0057627 92229448 1566072 1992 05 20 1992 05 20 2000 12 18

0036-8075 256 5054 1992 Apr 10 Positive control of pre-mRNA splicing in vitro. 237-40 Positive control of the sex-specific alternative splicing of doublesex (dsx) precursor messenger RNA (pre-mRNA) in Drosophila melanogaster involves the activation of a female-specific 3' splice site by the products of the transformer (tra) and transformer-2 (tra-2) genes. The mechanisms of this process were investigated in an in vitro system in which the female-specific 3' splice site could be activated by recombinant Tra or Tra-2 (or both). An exon sequence essential for regulation in vivo was shown to be both necessary and sufficient for activation in vitro. Nuclear proteins in addition to Tra and Tra-2 were found to bind specifically to this exon sequence. Therefore, Tra and Tra-2 may act by promoting the assembly of a multiprotein complex on the exon sequence. This complex may facilitate recognition of the adjacent 3' splice site by the splicing machinery. Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138. Tian M M Maniatis T T eng GM42231 GM NIGMS Journal Article

UNITED STATES Science 0404511 0 Nuclear Proteins 0 RNA Precursors 0 Recombinant Proteins 0 Ribonucleoproteins 0 transformer-2 protein 9004-22-2 Globins IM dsx tra tra-2 Animal Baculoviridae genetics Binding Sites Cell Nucleus metabolism Cloning, Molecular Drosophila melanogaster genetics Exons Female Globins genetics Hela Cells Human Male Nuclear Proteins genetics metabolism RNA Precursors genetics RNA Splicing Recombinant Proteins metabolism Ribonucleoproteins genetics metabolism Sex Characteristics Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0108438 99284528 10354481 1999 08 02 1999 08 02 2002 11 01

0925-4773 82 1-2 1999 Apr Molecular genetic analysis of the Drosophila trithorax-related gene which encodes a novel SET domain protein. 171-9 The products of the trithorax and Polycomb groups genes maintain the activity and silence, respectively, of many developmental genes including genes of the homeotic complexes. This transcriptional regulation is likely to involve modification of chromatin structure. Here, we report the cloning and characterization of a new gene, trithorax-related (trr), which shares sequence similarities with members of both the trithorax and Polycomb groups. The trr transcript is 9.6 kb in length and is present throughout development. The TRR protein, as predicted from the nucleotide sequence of the open reading frame, is 2431 amino acids in length and contains a PHD finger-like domain and a SET domain, two highly conserved protein motifs found in several trithorax and Polycomb group proteins, and in modifiers of position effect variegation. TRR is most similar in sequence to the human ALR protein, suggesting that trr is a Drosophila homologue of the ALR. TRR is also highly homologous to Drosophila TRITHORAX protein and to its human homologue, ALL-1/HRX. However, preliminary genetic analysis of a trr null allele suggests that TRR protein may not be involved in regulation of homeotic genes (i.e. not a member of the trithorax or Polycomb groups) or in position effect variegation. Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Sedkov Y Y Benes J J JJ Berger J R JR Riker K M KM Tillib S S Jones R S RS Mazo A A eng GM46567 GM NIGMS Journal Article

IRELAND Mech Dev 9101218 0 DNA Primers 0 DNA, Complementary 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 trithorax gene product IM Amino Acid Sequence Animal Animals, Genetically Modified Base Sequence Cloning, Molecular Comparative Study Conserved Sequence DNA Primers genetics DNA, Complementary genetics DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Female Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Homeodomain Proteins genetics Human Insect Proteins genetics Male Molecular Biology Molecular Sequence Data Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0111526 99423674 10491396 1999 10 12 1999 10 12 2001 11 02

0021-9525 146 6 1999 Sep 20 Apoptotic activities of wild-type and Alzheimer's disease-related mutant presenilins in Drosophila melanogaster. 1351-64 Mutant human presenilins cause early-onset familial Alzheimer's disease and render cells susceptible to apoptosis in cultured cell models. We show that loss of presenilin function in Drosophila melanogaster increases levels of apoptosis in developing tissues. Moreover, overexpression of presenilin causes apoptotic and neurogenic phenotypes resembling those of Presenilin loss-of-function mutants, suggesting that presenilin exerts a dominant negative effect when expressed at high levels. In Drosophila S2 cells, Psn overexpression leads to reduced Notch receptor synthesis affecting levels of the intact approximately 300-kD precursor and its approximately 120-kD processed COOH-terminal derivatives. Presenilin-induced apoptosis is cell autonomous and can be blocked by constitutive Notch activation, suggesting that the increased cell death is due to a developmental mechanism that eliminates improperly specified cell types. We describe a genetic model in which the apoptotic activities of wild-type and mutant presenilins can be assessed, and we find that Alzheimer's disease-linked mutant presenilins are less effective at inducing apoptosis than wild-type presenilin. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. Ye Y Y Fortini M E ME eng AG14583 AG NIA Journal Article

UNITED STATES J Cell Biol 0375356 0 Insect Proteins 0 Membrane Proteins 0 Peptide Fragments 0 Viral Proteins 0 inhibitor of apoptosis 1, Drosophila 0 inhibitor of apoptosis, nuclear polyhedrosis virus 0 notch protein 0 presenilin homolog, Drosophila IM Alleles Alzheimer Disease genetics Animal Animals, Genetically Modified Apoptosis Cell Line Drosophila melanogaster cytology genetics growth & development metabolism Eye cytology growth & development metabolism Gene Dosage Gene Expression Genes, Dominant genetics Insect Proteins genetics metabolism Membrane Proteins biosynthesis chemistry genetics metabolism Models, Genetic Mutation Peptide Fragments chemistry genetics metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Viral Proteins genetics metabolism Wing cytology growth & development metabolism FBrf0111379 99423881 10493744 1999 10 14 1999 10 14 2001 11 02

1529-2401 19 19 1999 Oct 1 Drosophila presenilin is required for neuronal differentiation and affects notch subcellular localization and signaling. 8435-42 Presenilins are a highly conserved family of proteins first identified as causative genes in early onset familial Alzheimer's disease. Recent studies have suggested a role for presenilins in the Notch-signaling pathway, but their specific function within this pathway remains unclear. Here, we have characterized the Drosophila presenilin gene and protein and studied their interaction with Notch in both mutants and transgenics. We find that the Drosophila presenilin protein is proteolytically cleaved and broadly expressed during development with the highest levels in neurons within the larval CNS. We also show that mutations in Drosophila presenilin (Dps) genetically interact with Notch and result in an early pupal-lethal phenotype characterized by defects in eye and wing development and incomplete neuronal differentiation within the larval CNS. Moreover, we find that processing of Notch in the Golgi by the furin protease is unaffected in Dps mutants and that Notch is present and may even accumulate on the plasma membrane of neuroblasts in the larval CNS of Dps mutants. In contrast, overexpression of Dps in transgenics causes Notch to accumulate in the cytoplasm. Taken together, these results indicate that Drosophila presenilin is required for proper neuronal differentiation and may regulate the subcellular localization of Notch proteins within cells, necessary for their accumulation and subsequent signaling capabilities. Program in Developmental Biology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8. Guo Y Y Livne-Bar I I Zhou L L Boulianne G L GL eng GENBANK AF093402 Journal Article

UNITED STATES J Neurosci 8102140 0 Membrane Proteins 0 notch protein 0 presenilin homolog, Drosophila IM Animal Animals, Genetically Modified Cell Differentiation Crosses, Genetic Drosophila melanogaster genetics physiology Gene Expression Regulation, Developmental Genes, Reporter Genes, Structural, Insect Larva Membrane Proteins genetics metabolism physiology Mutagenesis Neurons cytology physiology Phenotype Pupa Signal Transduction Support, Non-U.S. Gov't FBrf0151945 22308882 12421709 2002 11 07 2003 02 21

0950-1991 129 24 2002 Dec The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms. 5697-706 Photoreceptor differentiation in the Drosophila eye disc progresses from posterior to anterior in a wave driven by the Hedgehog and Decapentaplegic signals. Cells mutant for the hyperplastic discs gene misexpress both of these signaling molecules in anterior regions of the disc, leading to premature photoreceptor differentiation and overgrowth of surrounding tissue. The two genes are independently regulated by hyperplastic discs; decapentaplegic can still be misexpressed in cells mutant for both hyperplastic discs and hedgehog, and a repressor form of the transcription factor Cubitus interruptus can block decapentaplegic misexpression but not hedgehog misexpression. Loss of hyperplastic discs causes the accumulation of full-length Cubitus interruptus protein, but not of Smoothened, in both the eye and wing discs. hyperplastic discs encodes a HECT domain E3 ubiquitin ligase that is likely to act by targeting Cubitus interruptus and an unknown activator of hedgehog expression for proteolysis. Skirball Institute of Biomolecular Medicine and Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA. Lee Jeffrey D JD Amanai Kazuhito K Shearn Allen A Treisman Jessica E JE eng EY13777 EY NEI GM53058 GM NIGMS Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Ubiquitin 0 cubitus interruptus protein 0 dpp protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 6. Ligases EC 6.3.2. Peptide Synthases EC 6.3.2.- EDD protein, human EC 6.3.2.19 hyperplastic discs protein, Drosophila IM Animal Cell Differentiation DNA-Binding Proteins metabolism Drosophila Proteins biosynthesis physiology Drosophila melanogaster Immunohistochemistry Ligases biosynthesis metabolism physiology Microscopy, Fluorescence Models, Biological Mutation Peptide Synthases biosynthesis physiology Phenotype Protein Structure, Tertiary Signal Transduction Support, U.S. Gov't, P.H.S. Time Factors Ubiquitin metabolism FBrf0093154 97247726 9093849 1997 10 06 1997 10 06 2000 12 18

0016-6731 145 4 1997 Apr Competition between different variegating rearrangements for limited heterochromatic factors in Drosophila melanogaster. 945-59 Position effect variegation (PEV) results from the juxtaposition of a euchromatic gene to heterochromatin. In its new position the gene is inactivated in some cells and not in others. This mosaic expression is consistent with variability in the spread of heterochromatin from cell to cell. As many components of heterochromatin are likely to be produced in limited amounts, the spread of heterochromatin into a normally euchromatic region should be accompanied by a concomitant loss or redistribution of the protein components from other heterochromatic regions. We have shown that this is the case by simultaneously monitoring variegation of a euchromatic and a heterochromatic gene associated with a single chromosome rearrangement. Secondly, if several heterochromatic regions of the genome share limited components of heterochromatin, then some variegating rearrangements should compete for these components. We have examined this hypothesis by testing files with combinations of two or more different variegating rearrangements. Of the nine combinations of pairs of variegating rearrangements we studied, seven showed nonreciprocal interactions. These results imply that many components of heterochromatin are both shared and present in limited amounts and that they can transfer between chromosomal sites. Consequently, even nonvariegation portions of the genome will be disrupted by re-allocation of heterochromatic proteins associated with PEV. These results have implications for models of PEV. Department of Zoology, University of British Columbia, Vancouver, Canada. Lloyd V K VK Sinclair D A DA Grigliatti T A TA eng Journal Article

UNITED STATES Genetics 0374636 0 Heterochromatin IM Animal Chromosomes genetics ultrastructure Crosses, Genetic Drosophila melanogaster genetics Female Gene Expression Regulation Gene Rearrangement Heterochromatin genetics Male Models, Genetic Support, Non-U.S. Gov't FBrf0104438 98402481 9732269 1998 10 01 1998 10 01 2000 12 18

0890-9369 12 17 1998 Sep 1 okra and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. 2711-23 okra (okr), spindle-B (spnB), and spindle-D (spnD) are three members of a group of female sterile loci that produce defects in oocyte and egg morphology, including variable dorsal-ventral defects in the eggshell and embryo, anterior-posterior defects in the follicle cell epithelium and in the oocyte, and abnormalities in oocyte nuclear morphology. Many of these phenotypes reflect defects in grk-Egfr signaling processes, and can be accounted for by a failure to accumulate wild-type levels of Gurken and Fs(1)K10. We have cloned okr and spnB, and show that okr encodes the Drosophila homolog of the yeast DNA-repair protein Rad54, and spnB encodes a Rad51-like protein related to the meiosis-specific DMC1 gene. In functional tests of their role in DNA repair, we find that okr behaves like its yeast homolog in that it is required in both mitotic and meiotic cells. In contrast, spnB and spnD appear to be required only in meiosis. The fact that genes involved in meiotic DNA metabolism have specific effects on oocyte patterning implies that the progression of the meiotic cell cycle is coordinated with the regulation of certain developmental events during oogenesis. Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. Ghabrial A A Ray R P RP Schüpbach T T eng GENBANK AF069530 AF069531 PO1 CA 41086 CA NCI Journal Article

UNITED STATES Genes Dev 8711660 0 DNA-Binding Proteins 0 Egg Proteins 0 Rad52 protein 0 okra protein 0 spindle-B protein IM Amino Acid Sequence Animal Body Patterning genetics Cloning, Molecular DNA Repair DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics physiology Egg Proteins chemistry genetics metabolism Female Genes, Insect Genotype Infertility, Female genetics Molecular Sequence Data Nondisjunction, Genetic Oogenesis genetics Saccharomyces cerevisiae genetics Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome FBrf0134782 21168123 11267835 2001 03 27 2001 05 21

0027-5107 485 3 2001 Apr 4 Isolation and genetic characterisation of the Drosophila homologue of (SCE)REV3, encoding the catalytic subunit of DNA polymerase zeta. 237-53 In Drosophila, about 30 mutants are known that show hypersensitivity to the methylating agent methyl methane sulfonate (MMS). Addition of this agent to the medium results in an increased larval mortality of the mutants. Using a P-insertion mutagenesis screen, three MMS-sensitive mutants on chromosome II were isolated. One of these is allelic to the known EMS-induced mus205 (mutagen sensitive) mutant. In the newly isolated mutant, a P-element is detected in region 43E by in situ hybridisation. The localisation of mus205 to this region was confirmed by deficiency mapping. The gene was cloned and shows strong homology to the Saccharomyces cerevisiae REV3 gene. The REV3 gene encodes the catalytic subunit of DNA polymerase zeta, involved in translesion synthesis. The P-element is inserted in the first exon of the mus205 gene resulting in an aberrant mRNA, encoding a putative truncated protein containing only the first 13 of the 2130 aa native Drosophila protein. The mus205 mutant is hypersensitive to alkylating agents and UV, but not to ionising radiation. In contrast to reported data, in germ cells, the mutant has no effect on mutability by X-rays, NQO and alkylating agents. In somatic cells, the mutant shows no effect on MMS-induced mutations and recombinations. This phenotype of the Drosophila mus205 mutant is strikingly different from the phenotype of the yeast rev3 mutant, which is hypomutable after UV, X-rays, NQO and alkylating agents. Department of Radiation Genetics and Chemical Mutagenesis, MGC, Leiden University Medical Center, P.O. Box 9503, 2300 RF, Leiden, The Netherlands. j.c.j.eeken@lumc.nl Eeken J C JC Romeijn R J RJ de Jong A W AW Pastink A A Lohman P H PH eng Journal Article

Netherlands Mutat Res 0400763 0 DNA, Complementary 0 Mutagens 0 Protein Subunits 66-27-3 Methyl Methanesulfonate EC 2.7.7.- DNA Polymerase III EC 2.7.7.- DNA polymerase zeta EC 2.7.7.7 DNA-Directed DNA Polymerase IM Amino Acid Sequence Animal Catalytic Domain Cloning, Molecular Comparative Study DNA Polymerase III genetics DNA, Complementary genetics DNA-Directed DNA Polymerase genetics Drosophila melanogaster enzymology genetics Genes, Insect Methyl Methanesulfonate pharmacology Molecular Sequence Data Mutagenesis, Insertional Mutagens pharmacology Mutation Physical Chromosome Mapping Protein Subunits Radiation Tolerance genetics Recombination, Genetic Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0053347 92103681 1760843 1992 02 11 1992 02 11 2001 03 23

0092-8674 67 6 1991 Dec 20 The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development. 1157-67 Development of the Drosophila CNS midline cells is dependent upon the function of the single-minded (sim) gene. Sequence analysis shows that sim is a member of the basic-helix-loop-helix class of transcription factors. Cell fate experiments establish that sim is required for early events in midline cell development, including a synchronized cell division, proper formation of nerve cell precursors, and positive auto-regulation of its midline expression. Induction of ectopic sim protein under the control of the hsp70 promoter shows that sim can direct cells of the lateral CNS to exhibit midline cell morphology and patterns of gene expression. We propose that sim functions as a master developmental regulator of the CNS midline lineage. Department of Biology, University of California, Los Angeles 90024. Nambu J R JR Lewis J O JO Wharton K A KA Jr Crews S T ST eng GM-07185 GM NIGMS GM-08042 GM NIGMS R01 HD25251 HD NICHD Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 Nuclear Proteins 0 RNA, Messenger 0 Transcription Factors IM Lc MyoD arnt c-myc da lyl-1 sim twist Amino Acid Sequence Animal Central Nervous System embryology Comparative Study DNA Mutational Analysis DNA-Binding Proteins physiology Drosophila melanogaster embryology genetics Gene Expression Molecular Sequence Data Nuclear Proteins physiology RNA, Messenger genetics Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors physiology FBrf0068554 94088572 8264640 1994 01 21 1994 01 21 2000 12 18

0270-7306 14 1 1994 Jan The Drosophila dorsal morphogen represses the tolloid gene by interacting with a silencer element. 713-22 The dorsal protein (DL) regulates the transcriptional activity of several genes that determine cell fate along the dorsoventral axis of the Drosophila melanogaster embryo. DL is present at high levels in ventral nuclei, where it activates some genes (twi and sna) and represses others (zen, dpp, and tld). DL shows homology to the Rel family of proteins and interacts with specific DNA sequences in the regulatory regions of its target genes. The distal portion of the zen gene acts as a silencer that can mediate the repression of a heterologous promoter in ventral regions of the embryo. It contains four DL binding sites which alone are sufficient for activation but not repression. Here we analyze the interaction of DL with another one of its repressed targets, the tolloid (tld) gene. Approximately 800 bp of 5'-flanking sequences upstream of the tld coding region were shown to drive an expression pattern indistinguishable from the wild-type pattern. A 423-bp fragment located within these sequences contains two DL binding sites and was shown to act as a silencer to mediate ventral repression. Point mutations in the sites abolish not only DNA binding but also ventral repression. We discuss a comparison of the DNA sequences from the zen and tld promoters and the possible mechanisms of transcriptional silencing. Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110. Kirov N N Childs S S O'Connor M M Rushlow C C eng GM47462 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Nuclear Proteins 0 Phosphoproteins 0 dorsal protein, Drosophila 9007-49-2 DNA IM dpp tld zen Animal Base Sequence Binding Sites genetics DNA genetics Drosophila melanogaster embryology genetics metabolism Genes, Insect Genes, Regulator Molecular Sequence Data Nuclear Proteins genetics metabolism Phosphoproteins genetics metabolism Promoter Regions (Genetics) Support, U.S. Gov't, P.H.S. FBrf0152078 22213444 12225917 2002 09 12 2002 12 24

0965-1748 32 10 2002 Oct Design and function of transcriptional switches in Drosophila. 1257-73 Extensive genetic and biochemical analysis of Drosophila melanogaster has made this system an important model for characterization of transcriptional regulatory elements and factors. Given the striking conservation of transcriptional controls in metazoans, general principles derived from studies of Drosophila are expected to continue to illuminate transcriptional regulation in other systems, including vertebrates. With improvement in technologies for genetic manipulation of insects, research in Drosophila will also aid the design of systems for controlled expression of genes in other hosts. This review focuses on recent advances from Drosophila in analysis of the functional components of transcriptional switches, including basal promoters, enhancers, boundary elements, and maintenance elements. Michigan State University, Department of Biochemistry and Molecular Biology, East Lansing, MI 48824-1319, USA. arnosti@msu.edu Arnosti D N DN eng Journal Article Review Review, Academic

England Insect Biochem Mol Biol 9207282 IM Animal Drosophila melanogaster genetics Enhancer Elements (Genetics) Human Promoter Regions (Genetics) Support, U.S. Gov't, P.H.S. Transcription, Genetic 110 FBrf0054605 92001532 1911392 1991 11 01 1991 11 01 2000 12 18

0925-4773 34 1 1991 Mar Establishment of imaginal discs and histoblast nests in Drosophila. 11-20 In Drosophila the homeotic genes of the bithorax-complex (BX-C) and Antennapedia-complex (ANT-C) specify the identity of segments. Adult segment primordia are established in the embryo as the histoblast nests of the abdomen and the imaginal discs of the head, thorax and terminalia. We have used a molecular probe for the limb primordia and in vivo culture to describe the nature of the adult primordia in mutants in which the pattern of homeotic gene expression was altered. The results suggest that the histoblast or disc 'mode' of development is initiated by the extended germ band stage through activity of the BX-C and ANT-C and is relatively inflexible thereafter [corrected]. Department of Biology, Johns Hopkins University, Baltimore, Maryland. Simcox A A AA Hersperger E E Shearn A A Whittle J R JR Cohen S M SM eng Journal Article

IRELAND Mech Dev 9101218 EC 3.2.1.23 beta-Galactosidase IM Mech Dev 1991 Aug;35(1):73 Animal Drosophila melanogaster embryology Female Gene Expression Regulation Male Nucleic Acid Hybridization Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. beta-Galactosidase biosynthesis FBrf0151694 22284480 12397363 2002 10 24 2002 11 22

0028-0836 419 6909 2002 Oct 24 Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1. 857-62 The establishment and maintenance of mitotic and meiotic stable (epigenetic) transcription patterns is fundamental for cell determination and function. Epigenetic regulation of transcription is mediated by epigenetic activators and repressors, and may require the establishment, 'spreading' and maintenance of epigenetic signals. Although these signals remain unclear, it has been proposed that chromatin structure and consequently post-translational modification of histones may have an important role in epigenetic gene expression. Here we show that the epigenetic activator Ash1 (ref. 5) is a multi-catalytic histone methyl-transferase (HMTase) that methylates lysine residues 4 and 9 in H3 and 20 in H4. Transcriptional activation by Ash1 coincides with methylation of these three lysine residues at the promoter of Ash1 target genes. The methylation pattern placed by Ash1 may serve as a binding surface for a chromatin remodelling complex containing the epigenetic activator Brahma (Brm), an ATPase, and inhibits the interaction of epigenetic repressors with chromatin. Chromatin immunoprecipitation indicates that epigenetic activation of Ultrabithorax transcription in Drosophila coincides with trivalent methylation by Ash1 and recruitment of Brm. Thus, histone methylation by Ash1 may provide a specific signal for the establishment of epigenetic, active transcription patterns. Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. Beisel Christian C Imhof Axel A Greene Jaime J Kremmer Elisabeth E Sauer Frank F eng Journal Article

England Nature 0410462 0 ASH1 protein 0 Chromatin 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Histones 0 Transcription Factors 0 ultrabithorax protein IM Animal Cell Line Chromatin chemistry genetics metabolism DNA-Binding Proteins genetics Drosophila Proteins genetics metabolism Drosophila melanogaster genetics metabolism Enhancer Elements (Genetics) genetics Genes, Insect genetics Histones chemistry metabolism Methylation Mutation genetics Promoter Regions (Genetics) genetics Support, Non-U.S. Gov't Trans-Activation (Genetics) Transcription Factors genetics metabolism Transcription, Genetic genetics FBrf0064512 94067134 8246990 1994 01 03 1994 01 03 2000 12 18

0270-7306 13 12 1993 Dec Sex-lethal autoregulation requires multiple cis-acting elements upstream and downstream of the male exon and appears to depend largely on controlling the use of the male exon 5' splice site. 7734-46 The on/off state of the binary switch gene Sex-lethal (Sxl), which controls somatic sexual development in Drosophila melanogaster, is regulated at the level of alternative splicing. In males, in which the gene is off, the default splicing machinery produces nonfunctional mRNAs; in females, in which the gene is on, the autoregulatory activity of the Sxl proteins directs the splicing machinery to produce functional mRNAs. We have used germ line transformation to analyze the mechanism of default and regulated splicing. Our results demonstrate that a blockage mechanism is employed in Sxl autoregulation. However, in contrast to transformer, in which Sxl appears to function by preventing the interaction of splicing factors with the default 3' splice site, a different strategy is used in autoregulation. (i) Multiple cis-acting elements, both upstream and downstream of the male exon, are required. (ii) These cis-acting elements are distant from the splice sites they regulate, suggesting that the Sxl protein cannot function in autoregulation by directly competing with splicing factors for interaction with the regulated splice sites. (iii) The 5' splice site of the male exon appears to be dominant in regulation while the 3' splice site plays a subordinate role. Department of Molecular Biology, Princeton University, New Jersey 08544. Horabin J I JI Schedl P P eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA Primers 0 RNA, Messenger 27416-86-0 Poly U IM Sxl dsx lacZ tra Animal Base Sequence DNA Primers genetics Drosophila melanogaster genetics growth & development Exons Female Genes, Lethal Genes, Switch Homeostasis genetics Introns Male Models, Genetic Molecular Sequence Data Poly U genetics RNA Splicing genetics RNA, Messenger genetics Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0130036 20368159 10906453 2000 11 09 2000 11 09 2002 10 21

0925-4773 95 1-2 2000 Jul polyhomeotic controls engrailed expression and the hedgehog signaling pathway in imaginal discs. 89-99 Polycomb group (PcG) genes maintain cell identities during development in insects and mammals and their products are required in many developmental pathways. These include limb morphogenesis in Drosophila melanogaster, since PcG genes interact with identity and pattern specifying genes in imaginal discs and clones of polyhomeotic (ph) null cells induce abnormal limb patterning. Such clones are associated with ectopic expression of engrailed, hedgehog, patched, cubitus interruptus and decapentaplegic, in a compartment specific manner. Our results also reveal negative engrailed regulation by ph in both disc compartments: ph silences engrailed in anterior cells and maintains the level of engrailed expression in posterior ones. We suggest that PcG targets are not exclusively regulated by an on/off mechanism, but that the PcG also exerts negative transcriptional control on active genes. Centre de Génétique Moléculaire du C.N.R.S., UPR 2167, F-91198, Gif sur Yvette Cedex, France. randsholt@cgm.cnrs-gif.fr Randsholt N B NB Maschat F F Santamaria P P eng Journal Article

IRELAND Mech Dev 9101218 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 Nucleoproteins 0 engrailed protein 146888-72-4 polyhomeotic protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Homeodomain Proteins genetics Insect Proteins genetics Metamorphosis, Biological Mutation Nucleoproteins genetics Signal Transduction genetics Support, Non-U.S. Gov't FBrf0105925 99083441 9866209 1999 01 19 1999 01 19 2001 11 14

0737-4038 15 12 1998 Dec The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster. 1751-60 In a recent study, we reported that the combined average mutation rate of 10 di-, 6 tri-, and 8 tetranucleotide repeats in Drosophila melanogaster was 6.3 x 10(-6) mutations per locus per generation, a rate substantially below that of microsatellite repeat units in mammals studied to date (range = 10(-2)-10(-5) per locus per generation). To obtain a more precise estimate of mutation rate for dinucleotide repeat motifs alone, we assayed 39 new dinucleotide repeat microsatellite loci in the mutation accumulation lines from our earlier study. Our estimate of mutation rate for a total of 49 dinucleotide repeats is 9.3 x 10(-6) per locus per generation, only slightly higher than the estimate from our earlier study. We also estimated the relative difference in microsatellite mutation rate among di-, tri-, and tetranucleotide repeats in the genome of D. melanogaster using a method based on population variation, and we found that tri- and tetranucleotide repeats mutate at rates 6.4 and 8.4 times slower than that of dinucleotide repeats, respectively. The slower mutation rates of tri- and tetranucleotide repeats appear to be associated with a relatively short repeat unit length of these repeat motifs in the genome of D. melanogaster. A positive correlation between repeat unit length and allelic variation suggests that mutation rate increases as the repeat unit lengths of microsatellites increase. Section of Genetics and Development, Cornell University, Ithaca, New York 14853, USA. mds25@cornell.edu Schug M D MD Hutter C M CM Wetterstrand K A KA Gaudette M S MS Mackay T F TF Aquadro C F CF eng GENBANK AF091999 AF092000 AF092001 AF092002 AF092003 AF092004 AF092005 AF092006 AF092007 AF092008 AF092009 AF092010 AF092011 AF092012 AF092013 AF092014 AF092015 AF092016 AF092017 AF092018 AF092019 AF092020 AF092021 AF092022 AF092023 AF092024 AF092025 AF092026 AF092027 AF092028 Journal Article

UNITED STATES Mol Biol Evol 8501455 0 Genetic Markers IM S Africa Alleles Animal Dinucleotide Repeats Drosophila melanogaster genetics Evolution, Molecular Female Gene Library Genetic Markers Heterozygote Microsatellite Repeats Models, Genetic Mutation Polymerase Chain Reaction Regression Analysis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Time Trinucleotide Repeats United States FBrf0076498 95011573 7926760 1994 11 18 1994 11 18 2000 12 18

0890-9369 8 6 1994 Mar 15 Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila. 698-706 Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome. To explore the basis for the sex specificity of dosage compensation, we examined MSL-1 expression in males, females, and dosage compensation mutants. MSL-1 protein levels are negatively regulated by Sxl in females, resulting in male-specific expression of MSL-1. In addition, msl-2 is required for translation and/or stability of MSL-1 in males. Furthermore, the wild-type pattern of MSL-1 localization to the X chromosome is dependent on mle and msl-3 function, although a subset of sites are stained with MSL-1 antibodies in these mutants. Collectively, these data provide the first evidence for an order of msl gene function and suggest that male-specific expression of MSL-1 plays a key role in the sex specificity of dosage compensation. Department of Entomology, Oklahoma State University, Stillwater 74078. Palmer M J MJ Richman R R Richter L L Kuroda M I MI eng GM45744 GM NIGMS Journal Article

UNITED STATES Genes Dev 8711660 0 Nuclear Proteins 0 Transcription Factors 0 male-specific lethal-one protein IM Sx1 mle msl-1 msl-2 msl-3 Animal Blotting, Western Chromosome Mapping Comparative Study Crosses, Genetic Drosophila melanogaster genetics growth & development Female Gene Dosage Genes, Lethal Genotype Heterozygote Homozygote Larva Male Nuclear Proteins biosynthesis genetics Sex Characteristics Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors biosynthesis genetics FBrf0130102 20433229 10976041 2000 12 01 2000 12 01

0950-1991 127 19 2000 Oct The combgap locus encodes a zinc-finger protein that regulates cubitus interruptus during limb development in Drosophila melanogaster. 4083-93 The combgap locus, first described by C. B. Bridges in 1925, is a gene required for proper anteroposterior pattern formation in the limbs of Drosophila melanogaster. The development of the anteroposterior axis of fly limbs is initiated by hedgehog signaling from cells of the posterior half to cells of the anterior half of the limb primordium. Hedgehog signaling requires the anterior-specific expression of the gene cubitus interruptus to establish posterior-specific hedgehog secretion and anterior-specific competence to respond to hedgehog. We have cloned combgap and find that it encodes a chromosomal protein with 11 C(2)H(2) zinc fingers. Limb defects found in combgap mutants consist of either loss or duplication of pattern elements in the anteroposterior axis and can be explained through the inappropriate expression of cubitus interruptus and its downstream target genes. In combgap mutants, cubitus interruptus is ectopically expressed in the posterior compartments of wing imaginal discs and is downregulated in the anterior compartment of legs, wings and antennae. We are able to rescue anterior compartment combgap phenotypes by expressing additional cubitus interruptus using the Gal4/UAS system. Dominant alleles of cubitus interruptus, which result in posterior expression, phenocopy combgap posterior compartment phenotypes. Finally, we find that the combgap protein binds to polytene chromosomes at many sites including the cubitus interruptus locus, suggesting that it could be a direct regulator of cubitus interruptus transcription. Department of Biochemistry and Molecular Biology, and Genes and Development Research Group, Faculty of Medicine, University of Calgary, Calgary Alberta, T2N 4N1, Canada. Svendsen P C PC Marshall S D SD Kyba M M Brook W J WJ eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Transcription Factors 0 combgap protein 0 cubitus interruptus protein IM Animal Body Patterning genetics Cloning, Molecular DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Gene Duplication Gene Expression Regulation Genes, Insect Insect Proteins genetics metabolism Mutation Protein Binding Support, Non-U.S. Gov't Transcription Factors genetics metabolism Transcription, Genetic Wing embryology Zinc Fingers genetics FBrf0048107 89196890 3149249 1989 05 18 1989 05 18 2000 12 18

0890-9369 2 12B 1988 Dec Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates. 1723-35 Delta (D1) is required for normal segregation of the embryonic ectoderm into neural and epidermal cell lineages in Drosophila melanogaster. Loss-of-function mutations in D1 and other zygotic neurogenic loci lead to expansion of the neuroblast population at the expense of the dermoblast population within the ectoderm. Characterization of the transcriptional organization and maternal/embryonic expression within the chromosomal interval corresponding to D1 reveals that the locus encodes multiple transcripts: a minimum of two maternal transcripts, approximately 4.5 and 3.6 kb in length, and four zygotic transcripts, approximately 5.4 (two distinct species), 3.5, and 2.8 kb in length. These transcripts differ on the bases of differential splicing and differential polyadenylation site choice. The DNA sequence of a cDNA clone representing the predominant transcripts of the locus indicates that D1 encodes a transmembrane protein homologous to blood coagulation factors and epidermal growth factor. The relationship between coding sequences and transcript-specific exons within the locus suggests that D1 encodes multiple translational products. Department of Biology, Indiana University, Bloomington 47405. Kopczynski C C CC Alton A K AK Fechtel K K Kooh P J PJ Muskavitch M A MA eng GENBANK Y00222 Journal Article

UNITED STATES Genes Dev 8711660 0 Blood Coagulation Factors 0 Membrane Proteins 62229-50-9 Epidermal Growth Factor IM Amino Acid Sequence Animal Base Sequence Blood Coagulation Factors genetics Comparative Study Drosophila melanogaster embryology genetics Epidermal Growth Factor genetics Genes, Structural Immunoblotting Membrane Proteins genetics Molecular Sequence Data Neurons embryology Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Vertebrates genetics FBrf0039985 83244762 6408464 1983 08 11 1983 08 11 2000 12 18

0027-5107 107 2 1983 Feb High proportion of multi-locus deletions among hycanthone-induced X-linked recessive lethals in Drosophila melanogaster. 187-201 328 X-linked recessive lethal mutations induced in late spermatids by hycanthone methanesulfonate were tested for coverage by duplications that comprised, in total, about 24% of the euchromatic X chromosome; 78 lethals appeared to be covered. Crossover localization tests of a random sample of 38 non-covered lethals revealed 4 chromosomes carrying a lethal within a duplicated segment. Lethals localized to a particular region were crossed to reference deficiencies and single-locus mutations, and inter se, to ascertain their genetic extent. The proportion of multi-locus deletions among these 78 covered and 4 non-covered lethals was 3/48, 1/10 and 13/24 for the distal, medial and proximal regions, respectively. A storage period of 9 days did not noticeably influence these proportions. In the sample of 38 non-covered lethals, and among 17 of the covered single-site lethals, 4 cases of strong crossover suppression were detected. Comparison of these results with data obtained with other mutagens suggests that induction of multi-locus deletions, and possibly of other types of chromosome rearrangement, could in part depend on other mechanisms than those acting in the formation of translocations and chromosome loss. For the purpose of mutagen testing, these findings imply that, in Drosophila, results in the regular genetic tests for chromosome breakage events do not always accurately predict the capacity of a mutagen to induce multi-locus deletions. This is of importance since transmissible multi-locus deletions have been considered a significant source of genetic damage in man. Kramers P G PG Schalet A P AP Paradi E E Huiser-Hoogteyling L L eng Journal Article

NETHERLANDS Mutat Res 0400763 0 Thioxanthenes 3105-97-3 Hycanthone IM Animal Chromosome Deletion Comparative Study Drosophila melanogaster genetics Female Genes, Lethal drug effects Genes, Recessive drug effects Genetic Complementation Test Hycanthone pharmacology Linkage (Genetics) Male Mutagenicity Tests Mutation Spermatids drug effects Thioxanthenes pharmacology X Chromosome drug effects FBrf0125212 20119178 10652272 2000 02 25 2000 02 25 2003 03 28

0890-9369 14 2 2000 Jan 15 Rhomboid and Star facilitate presentation and processing of the Drosophila TGF-alpha homolog Spitz. 177-86 Activation of the Drosophila epidermal growth factor receptor (DER) by the transmembrane ligand, Spitz (Spi), requires two additional transmembrane proteins, Rhomboid and Star. Genetic evidence suggests that Rhomboid and Star facilitate DER signaling by processing membrane-bound Spi (mSpi) to an active, soluble form. To test this model, we use an assay based on Xenopus animal cap explants in which Spi activation of DER is Rhomboid and Star dependent. We show that Spi is on the cell surface but is kept in an inactive state by its cytoplasmic and transmembrane domains; Rhomboid and Star relieve this inhibition, allowing Spi to signal. We show further that Spi is likely to be cleaved within its transmembrane domain. However, a mutant form of mSpi that is not cleaved still signals to DER in a Rhomboid and Star-dependent manner. These results suggest strongly that Rhomboid and Star act primarily to present an active form of Spi to DER, leading secondarily to the processing of Spi into a secreted form. Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 USA. Bang A G AG Kintner C C eng Journal Article

UNITED STATES Genes Dev 8711660 0 Insect Proteins 0 Membrane Proteins 0 Phosphoproteins 0 Receptors, Invertebrate Peptide 0 Rho protein, Drosophila 0 Transforming Growth Factor alpha 0 epidermal growth factor receptor homolog, Drosophila 0 rho-2 protein, Drosophila 0 steroidogenic acute regulatory protein 148175-53-5 spitz protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Biological Assay Cell Membrane metabolism Cytoplasm metabolism Drosophila melanogaster embryology physiology Human Hydrolysis Insect Proteins physiology Membrane Proteins metabolism physiology Phosphoproteins physiology Protein Processing, Post-Translational Protein Structure, Tertiary Receptor, Epidermal Growth Factor metabolism physiology Receptors, Invertebrate Peptide metabolism physiology Sequence Homology, Amino Acid Signal Transduction physiology Solubility Support, U.S. Gov't, P.H.S. Transforming Growth Factor alpha metabolism Xenopus laevis FBrf0155784 22456600 12568721 2003 02 05 2003 04 09

0378-1119 304 2003 Jan 30 Serine proteases and their homologs in the Drosophila melanogaster genome: an initial analysis of sequence conservation and phylogenetic relationships. 117-31 Serine proteases (SPs) and serine protease homologs (SPHs) constitute the second largest family of genes in the Drosophila melanogaster genome. Eighty-four SPs comprise less than 300 amino acid residues, and a significant portion of them are probably digestive enzymes. Some larger SPs may contain one or more regions important for protein-protein interactions, including clip domains, low-density lipoprotein receptor class A repeats, and scavenger receptor cysteine-rich domains. We identified 37 clusters of SP or SPH genes, which probably evolved from relatively recent gene duplication and sequence divergence. A majority of the SPs may be trypsin-like and activated by cleavage after a specific arginine or lysine residue. Among the 147 SPs and 57 SPHs studied, 24 SPs and 13 SPHs contain at least one regulatory clip domain. A multiple sequence alignment of the clip domains provided further information on structural conservation of these regulatory modules. Detailed sequence comparison led to an improved classification system for SPs containing clip domains. These analyses have established a framework of information about evolutionary relationships among the Drosophila SPs and SPHs, which may facilitate research on these proteins as well as homologous molecules from other invertebrate species. Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078, USA. Ross Jeremy J Jiang Haobo H Kanost Michael R MR Wang Yang Y eng GM41247 GM NIGMS GM58634 GM NIGMS Journal Article

Netherlands Gene 7706761 0 Drosophila Proteins EC 3.4.21 Serine Endopeptidases IM Amino Acid Sequence Animal Catalytic Domain genetics Chromosome Mapping Conserved Sequence genetics Databases, Protein Drosophila Proteins genetics Drosophila melanogaster enzymology genetics Expressed Sequence Tags Genome Molecular Sequence Data Phylogeny Sequence Alignment Sequence Homology, Amino Acid Serine Endopeptidases genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0105255 99009079 9792678 1998 12 10 1998 12 10 2000 12 18

0021-9258 273 45 1998 Nov 6 Cortactin associates with the cell-cell junction protein ZO-1 in both Drosophila and mouse. 29672-7 Cortactin is an actin filament-binding protein localizing at cortical regions of cells and a prominent substrate for Src family protein-tyrosine kinases in response to multiple extracellular stimuli. Human cortactin has been identified as a protein product of a putative oncogene, EMS1. In this report, we describe the identification of a Drosophila homolog of cortactin as a molecule that interacts with Drosophila ZO-1 using yeast two-hybrid screening. Drosophila cortactin is a 559-amino acid protein highly expressed in embryos, larvae, and pupae but relatively underexpressed in adult flies. Deletion and substitution mutant analyses revealed that the SH3 domain of Drosophila cortactin binds to a PXXP motif in the proline-rich domain of Drosophila ZO-1. Colocalization of these proteins at cell-cell junction sites was evident under a confocal laser-scanning microscope. In vivo association was confirmed by coimmunoprecipitation of cortactin and ZO-1 from Drosophila embryo lysates. We also demonstrate an association for each of the murine homologs by immunoprecipitation analyses of mouse tissue lysates. Our previous work has demonstrated the involvement of ZO-1 in a signaling pathway that regulates expression of the emc gene in Drosophila. The potential roles of the cortactin.ZO-1 complex in cell adhesion and cell signaling are discussed. Neurogenetics Research Project, Mitsubishi Kasei Institute of Life Sciences, Minamiooya 11, Machida-shi, Tokyo 194-8511, Japan. Katsube T T Takahisa M M Ueda R R Hashimoto N N Kobayashi M M Togashi S S eng GENBANK AB009998 Journal Article

UNITED STATES J Biol Chem 2985121R 0 DNA Primers 0 DNA, Complementary 0 Membrane Proteins 0 Microfilament Proteins 0 Phosphoproteins 0 Recombinant Proteins 0 cortactin 0 zonula occludens-1 protein IM Amino Acid Sequence Animal Base Sequence Cell Adhesion DNA Primers DNA, Complementary Drosophila melanogaster metabolism Human Immunohistochemistry Membrane Proteins metabolism Mice Microfilament Proteins genetics metabolism Molecular Sequence Data Phosphoproteins metabolism Protein Binding Recombinant Proteins metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't src Homology Domains FBrf0079093 95113176 7813777 1995 02 09 1995 02 09 2003 06 16

0012-1606 166 2 1994 Dec Characterization of tolloid-related-1: a BMP-1-like product that is required during larval and pupal stages of Drosophila development. 569-86 The Drosophila tolloid (tld) gene product belongs to a family of developmentally important proteins that includes bone morphogenetic protein-1 (BMP-1). In Drosophila, tld is required at the blastoderm stage to establish pattern within the dorsal half of the embryo. Genetic analysis suggests that the major function of tld is to augment the activity of the decapentaplegic gene product, a close relative of the TGF-beta superfamily members, BMP-2 and BMP-4. In this report, we describe a new gene called tolloid-related-1 (tlr-1) that maps immediately proximal to tld. Sequence analysis indicates that tlr-1 has a large N-terminal extension relative to tld, but otherwise shows the same general organization of sequence motifs found in tld and other BMP-1 family members. These include a region of similarity to astacin, a crayfish metalloprotease, five copies of a repeat first found in complement proteins C1r and C1s, and two copies of an epidermal growth factor-like sequence. In situ hybridization experiments show that tlr-1 expression partially overlaps tld expression in early embryos, but shows unique transcriptional patterns in late stage embryos that are not seen with tld. In larval stages, both genes are expressed in identical patterns in imaginal discs and in the optic lobes of the brain, but tlr-1 is more abundant than tld. Deletions that eliminate tlr-1 expression cause lethality during larval and pupal stages of development. A small proportion of homozygous mutant flies eclose and show wing veination defects. Transgenic animals in which a tlr-1 cDNA is driven by the tld promoter fail to rescue tld mutations, and extra copies of tld fail to rescue tlr-1 mutations, implying that these genes have evolved functionally distinct features. We propose that tld and tlr-1 arose by gene duplication and that each has evolved independently to acquire distinct tissue specific roles in Drosophila development. Department of Molecular Biology and Biochemistry, University of California, Irvine 92717. Nguyen T T Jamal J J Shimell M J MJ Arora K K O'Connor M B MB eng GENBANK U12634 GM 00599 GM NIGMS GM47462 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 0 Bone Morphogenetic Proteins 0 DNA Primers 0 Growth Substances 0 Insect Hormones 0 Proteins 0 RNA, Messenger 0 Tok protein, Drosophila 144714-21-6 tld protein, Drosophila IM BMP-1 tld tlr-1 Amino Acid Sequence Animal Base Sequence Bone Morphogenetic Proteins Cloning, Molecular Comparative Study DNA Primers chemistry Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Genes, Structural, Insect Growth Substances physiology Insect Hormones physiology Larva Molecular Sequence Data Morphogenesis Multigene Family Mutagenesis, Insertional Proteins chemistry physiology Pupa RNA, Messenger genetics Restriction Mapping Sequence Alignment Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. FBrf0053349 91292522 1648449 1991 08 13 1991 08 13 2000 12 18

0092-8674 65 7 1991 Jun 28 Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product. 1191-201 The maternal gene dorsal encodes a nuclear protein acting as a morphogen that determines the size and fate of regions along the dorsal-ventral axis of the Drosophila embryo. From previous genetic and biochemical studies it was hypothesized that dorsal might be responsible for the activation of the zygotic gene twist. In this report, regulatory sequences required for correct spatial and quantitative expression of twist are defined, by using phenotypic rescue and studying twist-beta-galactosidase expression. In addition, by transient cotransfection assays, we show that the dorsal protein specifically activates expression from the twist promoter. We demonstrate that dorsal is a sequence-specific DNA-binding protein that recognizes a motif similar to that recognized by the mammalian transcriptional activator NF-kappa B. Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France. Thisse C C Perrin-Schmitt F F Stoetzel C C Thisse B B eng Journal Article

UNITED STATES Cell 0413066 0 DNA Transposable Elements 0 DNA-Binding Proteins 0 Nuclear Proteins 0 Recombinant Proteins 0 dorsal protein, Drosophila 0 twist protein IM Animal Base Sequence DNA Mutational Analysis DNA Transposable Elements DNA-Binding Proteins physiology Drosophila melanogaster genetics Gene Expression Regulation Molecular Sequence Data Morphogenesis Nuclear Proteins physiology Promoter Regions (Genetics) Recombinant Proteins metabolism Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't Transcription, Genetic FBrf0042036 86079533 3000609 1986 02 12 1986 02 12 2000 12 18

0092-8674 43 2 Pt 1 1985 Dec The Sex-lethal gene of Drosophila: DNA alterations associated with sex-specific lethal mutations. 521-9 Genomic DNA encoding Sex-lethal, a developmental switch gene in Drosophila melanogaster that regulates sex determination and dosage compensation has been isolated. Wild-type DNA sequence organization of the gene has been compared at the restriction level with those of 17 female-specific, loss-of-function and five male-specific, gain-of-function mutant alleles. DNA lesions associated with 12 of these mutations delimit an 11 kb DNA region that is necessary for proper Sex-lethal function in females. Males who are deleted for this region are both viable and fertile. Loss-of-function alleles are associated with gross DNA alterations as well as true point mutations; the former are located throughout the region. In contrast, all five gain-of-function alleles are associated with DNA insertions that are clustered within a 1 kb portion of the Sxl gene region. Maine E M EM Salz H K HK Cline T W TW Schedl P P eng Journal Article

UNITED STATES Cell 0413066 0 DNA Transposable Elements 9007-49-2 DNA IM Alleles Animal Chromosome Mapping Cloning, Molecular DNA genetics DNA Transposable Elements Drosophila melanogaster genetics Female Genes, Dominant Genes, Lethal Genetic Complementation Test Inversion (Genetics) Male Morphogenesis Sex Characteristics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0049878 89137942 2492966 1989 04 06 1989 04 06 2000 12 18

0016-6731 121 1 1989 Jan Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations. 101-17 In mutagenesis screens for recessive female sterile mutations on the second chromosome of Drosophila melanogaster 529 chromosomes were isolated which allow the homozygous females to survive, but cause them to be sterile. In 136 of these lines, mutant females produce morphologically normal eggs which cannot support normal embryonic development. These "maternal-effect" mutations fall into 67 complementation groups which define 23 multiply hit and 44 singly hit loci. In eggs from 14 complementation groups development is blocked before the formation of a syncytial blastoderm. In eggs from 12 complementation groups development is abnormal before cellularization, 17 complementation groups cause abnormal cellularization, 12 complementation groups cause changes in cellular morphology in early gastrulation stages, and 12 complementation groups seem to affect later embryonic development. Biology Department, Princeton University, New Jersey 08544. Schüpbach T T Wieschaus E E eng HD 15587 HD NICHD Journal Article

UNITED STATES Genetics 0374636 62-50-0 Ethyl Methanesulfonate IM Animal Blastoderm cytology Chromosome Mapping Chromosomes Crosses, Genetic Drosophila melanogaster embryology genetics Ethyl Methanesulfonate Female Fertility Gastrula cytology Genetic Complementation Test Homozygote Mutation Oogenesis Ovum cytology Phenotype Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Zygote cytology FBrf0108393 99187150 10085257 1999 07 19 1999 07 19 2002 11 01

0021-9533 112 ( Pt 8) 1999 Apr Dcdc42 acts in TGF-beta signaling during Drosophila morphogenesis: distinct roles for the Drac1/JNK and Dcdc42/TGF-beta cascades in cytoskeletal regulation. 1225-35 During Drosophila embryogenesis the two halves of the lateral epidermis migrate dorsally over a surface of flattened cells, the amnioserosa, and meet at the dorsal midline in order to form the continuous sheet of the larval epidermis. During this process of epithelial migration, known as dorsal closure, signaling from a Jun-amino-terminal-kinase cascade causes the production of the secreted transforming-growth-factor-beta-like ligand, Decapentaplegic. Binding of Decapentaplegic to the putative transforming-growth-factor-beta-like receptors Thickveins and Punt activates a transforming-growth-factor-beta-like pathway that is also required for dorsal closure. Mutations in genes involved in either the Jun-amino-terminal-kinase cascade or the transforming-growth-factor-beta-like signaling pathway can disrupt dorsal closure. Our findings show that although these pathways are linked they are not equivalent in function. Signaling by the Jun-amino-terminal-kinase cascade may be initiated by the small Ras-like GTPase Drac1 and acts to assemble the cytoskeleton and specify the identity of the first row of cells of the epidermis prior to the onset of dorsal closure. Signaling in the transforming-growth-factor-beta-like pathway is mediated by Dcdc42, and acts during the closure process to control the mechanics of the migration process, most likely via its putative effector kinase DPAK. Drosophila Neurobiology Laboratory and Glaxo-IMCB Group, Institute of Molecular and Cell Biology, Singapore 117609, Republic of Singapore. Ricos M G MG Harden N N Sem K P KP Lim L L Chia W W eng Journal Article

ENGLAND J Cell Sci 0052457 0 Dcdc42 protein 0 Drac1 protein 0 Receptors, Cell Surface 0 Transforming Growth Factor beta EC 2.7.1.- DTFR protein, Drosophila EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.10.- c-Jun amino-terminal kinase EC 3.6.1.- GTP-Binding Proteins IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase physiology Cytoskeleton metabolism Drosophila melanogaster embryology genetics Epidermis metabolism GTP-Binding Proteins physiology Immunohistochemistry Microscopy, Confocal Microscopy, Fluorescence Models, Genetic Morphogenesis Protein-Serine-Threonine Kinases metabolism Receptors, Cell Surface metabolism Signal Transduction Support, Non-U.S. Gov't Transforming Growth Factor beta physiology Transgenes FBrf0045782 88052886 2890438 1988 01 12 1988 01 12 2000 12 18

0092-8674 51 5 1987 Dec 4 A complex genetic locus, polyhomeotic, is required for segmental specification and epidermal development in D. melanogaster. 829-39 Two mutagenic events are required to make null mutations of polyhomeotic (ph), which suggests that the locus is complex. Amorphic mutations (ph degrees) die in mid-embryogenesis and completely lack ventral thoracic and abdominal epidermal derivatives, whereas single-event mutations lead to transformations similar to those of known dominant gain of function mutants in the Antennapedia and bithorax complexes. After a chromosomal walk, the ph gene was localized using deficiencies and ph mutations that result from DNA rearrangements. Hybridization analyses show that there are two large, duplicated sequences in the ph region, and DNA lesions affecting either one of these repeats alter the function of the ph locus. We propose a model that may account for this unusual functional organization. Centre de Génétique Moleculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France. Dura J M JM Randsholt N B NB Deatrick J J Erk I I Santamaria P P Freeman J D JD Freeman S J SJ Weddell D D Brock H W HW eng Journal Article

UNITED STATES Cell 0413066 IM Alleles Animal Chromosome Mapping Cleavage Stage, Ovum Drosophila melanogaster embryology genetics Epidermis embryology Genes, Homeobox Genes, Structural Mutation Phenotype Support, Non-U.S. Gov't Transcription, Genetic FBrf0072848 94350209 8070664 1994 09 27 1994 09 27 2000 12 18

0016-6731 137 2 1994 Jun Molecular analysis of the Drosophila EGF receptor homolog reveals that several genetically defined classes of alleles cluster in subdomains of the receptor protein. 531-50 Mutations in the torpedo gene, which encodes the fruitfly homolog of the epidermal growth factor receptor (DER), disrupt a variety of developmental processes in Drosophila. These include the survival of certain embryonic ectodermal tissues, the proliferation of the imaginal discs, the morphogenesis of several adult ectodermal structures and oogenesis, torpedo is genetically complex: a number of alleles of the gene differentially affect the development of specific tissues, such as the eye, wing, bristles and ovary. In addition, torpedo mutations exhibit interallelic complementation. Molecular analysis of 24 loss-of-function mutations in the torpedo gene provides insights into the mechanistic basis of its genetic complexity. We observe an intriguing correlation between molecular lesions and mutant phenotypes. Alleles that differentially affect specific developmental processes encode receptors with altered extracellular domains. Alleles that fully or partially complement a wide range of embryonic and postembryonic torpedo mutations encode receptors with altered intracellular domains. From these findings we conclude the following. First, the torpedo protein may be activated by tissue-specific ligands. Second, the torpedo receptor tyrosine kinase may phosphorylate multiple substrates. Third, signal transduction by torpedo appears to require the physical association of receptors. Finally, the extracellular domain of the Torpedo protein may play an essential role in mediating receptor-receptor interactions. Department of Molecular Biology, Princeton University, New Jersey 08544-1003. Clifford R R Schüpbach T T eng GENBANK S73522 S73523 S73524 GM40558 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Alleles Amino Acid Sequence Animal Base Sequence Comparative Study Conserved Sequence Crosses, Genetic Drosophila melanogaster embryology genetics Embryo, Nonmammalian cytology physiology Exons Female Genes, Insect Genes, Lethal Genetic Complementation Test Human Male Molecular Sequence Data Mosaicism Multigene Family Mutagenesis Phosphorylation Point Mutation Polymerase Chain Reaction Receptor, Epidermal Growth Factor genetics metabolism Sequence Deletion Sequence Homology, Amino Acid Signal Transduction Support, U.S. Gov't, P.H.S. FBrf0152247 22194796 12198500 2002 09 02 2002 10 11

1465-7392 4 9 2002 Sep Invasive cell migration is initiated by guided growth of long cellular extensions. 715-9 The migration of border cells during Drosophila melanogaster oogenesis is a simple and powerful system for studying invasive cell migration in vivo. Border cells are somatic cells that delaminate from the follicular epithelium of an egg chamber and invade the germ line cluster. They migrate between the nurse cells to reach the oocyte, using DE-cadherin for adhesion to the substratum. Border cells take approximately 6 h to migrate a distance of 100 microm. The migration is guided by EGFR (epidermal growth factor receptor) and PVR (platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) receptor). Here, we show that a single long cellular extension (LCE), several cell diameters in length, is formed at the initiation of migration. The LCE may function as a 'pathfinder' in response to guidance cues. LCE growth requires directional guidance signals and specific adhesion to the substratum. Interference with actin-myosin interactions allows continued LCE growth while preventing translocation of the cell bodies. We discuss similarities between LCEs and axons and the use of LCE-like structures as a general mechanism for initiating invasive migration in vivo. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Fulga Tudor A TA Rørth Pernille P eng Journal Article

England Nat Cell Biol 100890575 0 Actins 0 Cadherins 0 Drosophila Proteins 0 Egg Proteins 0 Luminescent Proteins 0 PDGF-VEGF factor 1 147336-22-9 green fluorescent protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Nat Cell Biol. 2002 Sep;4(9):E211-2 12205482 Actins physiology Animal Animals, Genetically Modified Cadherins physiology Cell Movement physiology Drosophila Proteins physiology Drosophila melanogaster cytology genetics growth & development physiology Egg Proteins physiology Female Genes, Insect Lac Operon Luminescent Proteins genetics Mutation Oogenesis physiology Receptor, Epidermal Growth Factor physiology Signal Transduction Support, Non-U.S. Gov't FBrf0125155 20156399 10689194 2000 03 24 2000 03 24 2000 12 18

0378-1119 244 1-2 2000 Feb 22 Hyperactivation of the Drosophila Hop jak kinase causes the preferential overexpression of eIF1A transcripts in larval blood cells. 119-25 Jak kinase-Stat protein pathways play a critical role in the response of blood cells to a range of cytokines and growth factors. We are using the fruit fly, Drosophila melanogaster, as a model system to elucidate additional components of Jak-Stat pathways, and to determine how abnormalities in this pathway lead to hematopoietic leukemia-like defects. To identify downstream targets, we conducted a molecular screen for genes whose transcripts are overexpressed in response to activation of the Drosophila Hop Jak kinase. We identified a Drosophila homolog of eIF1A, a eukaryotic initiation factor found in humans and other eukaryotes. D-eIF1A is highly overexpressed in the hemocytes and lymph glands of third instar larvae carrying the dominant, gain-of-function mutation hop(Tum-l). A quantitative comparison of poly(A)(+) RNA levels between D-eIF1A and other known Drosophila translation initiation factors indicates that D-eIF1A transcripts preferentially overaccumulate in response to the hyperactive Hop pathway. Our results support the model that D-eIF1A is one of the target genes through which the Drosophila Jak kinase pathway regulates hemocyte development. Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Myrick K V KV Dearolf C R CR eng GENBANK AF169359 Journal Article

NETHERLANDS Gene 7706761 0 DNA, Complementary 0 Peptide Initiation Factors 0 RNA, Messenger 0 eIF-4C EC 2.7.1.- Hop protein EC 2.7.1.112 Protein-Tyrosine Kinase IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping DNA, Complementary chemistry genetics Drosophila enzymology genetics growth & development Enzyme Activation Gene Expression Regulation, Developmental Genes, Structural genetics Hemocytes cytology metabolism Larva enzymology genetics Molecular Sequence Data Peptide Initiation Factors genetics Protein-Tyrosine Kinase metabolism RNA, Messenger genetics metabolism Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Sequence Analysis, DNA Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0135946 21189483 11292874 2001 04 09 2001 06 07 2003 06 16

0036-8075 292 5514 2001 Apr 6 Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. 104-6 The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway. In the nematode Caenorhabditis elegans, insulin/IGF signaling regulates adult longevity. We found that mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes. Extension of life-span was not a result of impaired oogenesis in chico females, nor was it consistently correlated with increased stress resistance. The dwarf phenotype of chico homozygotes was also unnecessary for extension of life-span. The role of insulin/IGF signaling in regulating animal aging is therefore evolutionarily conserved. Department of Biology, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK. Clancy D J DJ Gems D D Harshman L G LG Oldham S S Stocker H H Hafen E E Leevers S J SJ Partridge L L eng Journal Article

United States Science 0404511 0 Carrier Proteins 0 INR protein 0 Insect Proteins 0 Somatomedins 0 chico protein, Drosophila 11061-68-0 Insulin EC 1.15.1.1 Superoxide Dismutase EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Insulin IM Science. 2001 Apr 6;292(5514):41-3 11294208 Aging physiology Alleles Animal Body Constitution Carrier Proteins genetics metabolism Crosses, Genetic Drosophila melanogaster genetics physiology Female Fertility Genes, Insect Heat Heterozygote Insect Proteins genetics metabolism Insulin metabolism Longevity physiology Male Mutation Oxidative Stress Protein-Tyrosine Kinase genetics metabolism Receptor, Insulin metabolism Reproduction Signal Transduction Somatomedins metabolism Starvation Superoxide Dismutase Support, Non-U.S. Gov't FBrf0126731 20172065 10704400 2000 04 25 2000 04 25 2003 06 02

0960-9822 10 4 2000 Feb 24 Cell death: drosophila Apaf-1 - no longer in the (d)Ark. R167-9 The recent discovery and characterization of Ark, the Drosophila homolog of the mammalian cell-death adaptor protein Apaf-1, have revealed that, like Apaf-1, this protein is important in multiple apoptosis pathways. The new findings also suggest that cell death in flies is very similar to that in mammals after all. Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. kristin.white@CBRC2.MGH.Harvard.edu White K K eng Journal Article

ENGLAND Curr Biol 9107782 0 Apaf-1 protein 0 Ark protein, Drosophila 0 Proteins IM Animal Apoptosis Drosophila melanogaster Proteins physiology FBrf0123199 20105214 10637305 2000 04 07 2000 04 07 2000 12 18

1059-1524 11 1 2000 Jan Functional coordination of three mitotic motors in Drosophila embryos. 241-53 It is well established that multiple microtubule-based motors contribute to the formation and function of the mitotic spindle, but how the activities of these motors interrelate remains unclear. Here we visualize spindle formation in living Drosophila embryos to show that spindle pole movements are directed by a temporally coordinated balance of forces generated by three mitotic motors, cytoplasmic dynein, KLP61F, and Ncd. Specifically, our findings suggest that dynein acts to move the poles apart throughout mitosis and that this activity is augmented by KLP61F after the fenestration of the nuclear envelope, a process analogous to nuclear envelope breakdown, which occurs at the onset of prometaphase. Conversely, we find that Ncd generates forces that pull the poles together between interphase and metaphase, antagonizing the activity of both dynein and KLP61F and serving as a brake for spindle assembly. During anaphase, however, Ncd appears to have no effect on spindle pole movements, suggesting that its activity is down-regulated at this time, allowing dynein and KLP61F to drive spindle elongation during anaphase B. Section of Molecular and Cellular Biology, University of California-Davis, Davis, California 95616, USA. Sharp D J DJ Brown H M HM Kwon M M Rogers G C GC Holland G G Scholey J M JM eng GM-19262 GM NIGMS GM-55507 GM NIGMS Journal Article

UNITED STATES Mol Biol Cell 9201390 0 Molecular Motors IM Anaphase physiology Animal Blastoderm ultrastructure Drosophila melanogaster embryology Female Human Interphase physiology Male Metaphase physiology Microtubules ultrastructure Mitosis physiology Mitotic Spindle Apparatus physiology ultrastructure Molecular Motors Prophase physiology Support, U.S. Gov't, P.H.S. FBrf0090580 97108732 8951053 1997 01 23 1997 01 23 2003 03 28

0950-1991 122 11 1996 Nov The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm. 3363-70 The Drosophila EGF receptor (DER) is activated by secreted Spitz to induce different cell fates in the ventral ectoderm. Processing of the precursor transmembrane Spitz to generate the secreted form was shown to be the limiting event, but the cells in which processing takes place and the mechanism that may generate a gradient of secreted Spitz in the ectoderm were not known. The ectodermal defects in single minded (sim) mutant embryos, in which the midline fails to develop, suggested that the midline cells contribute to patterning of the ventral ectoderm. This work shows that the midline provides the site for Spitz expression and processing. The Rhomboid and Star proteins are also expressed and required in the midline. The ectodermal defects of spitz, rho or Star mutant embryos could be rescued by inducing the expression of the respective normal genes only in the midline cells. Rho and Star thus function non-autonomously, and may be required for the production or processing of the Spitz precursor. Secreted Spitz is the only sim-dependent contribution of the midline to patterning the ectoderm, since the ventral defects observed in sim mutant embryos can be overcome by expression of secreted Spitz in the ectoderm. While ectopic expression of secreted Spitz in the ectoderm or mesoderm gave rise to ventralization of the embryo, increased expression of secreted Spitz in the midline did not lead to alterations in ectoderm patterning. A mechanism for adjustment to variable levels of secreted Spitz emanating from the midline may be provided by Argos, which forms an inhibitory feedback loop for DER activation. The production of secreted Spitz in the midline, may provide a stable source for graded DER activation in the ventral ectoderm. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. Golembo M M Raz E E Shilo B Z BZ eng Journal Article

ENGLAND Development 8701744 0 Membrane Proteins 0 Phosphoproteins 0 Rho protein, Drosophila 0 rho-2 protein, Drosophila 0 steroidogenic acute regulatory protein 148175-53-5 spitz protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Cell Differentiation Drosophila melanogaster embryology Ectoderm physiology Gene Expression Regulation, Developmental Membrane Proteins physiology Mesoderm physiology Morphogenesis Phosphoproteins physiology Receptor, Epidermal Growth Factor physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0055563 93046644 1358457 1992 12 08 1992 12 08 2000 12 18

0092-8674 71 3 1992 Oct 30 Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. 437-50 Homeotic genes encode transcription factors that are thought to specify segmental identity by regulating expression of subordinate genes. Limb development is repressed in the abdominal segments of the Drosophila embryo by the hometic genes of the Bithorax complex (BX-C). Localized expression of the homeobox gene Distal-less (DII) is required for leg development in thoracic segments. We have identified a minimal cis-regulatory enhancer element that directs DII expression in the larval leg primordia. We present evidence that the BX-C proteins repress DII expression in abdominal segments by binding to a small number of specific sites in this element. Mutating these sites eliminates BX-C protein binding and renders the element insensitive to BX-C-mediated repression in vivo. Repression of limb development in the abdomen appears to be controlled at the DII enhancer. Thus DII may serve as a downstream target gene through which the homeotic genes control abdominal segment identity in the Drosophila embryo. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030. Vachon G G Cohen B B Pfeifle C C McGuffin M E ME Botas J J Cohen S M SM eng GENBANK L02539 S47136 S47137 S47164 S47165 S47166 S47167 S47168 S47947 S47948 S72771 Journal Article

UNITED STATES Cell 0413066 0 Repressor Proteins IM Distal-less Dll Amino Acid Sequence Animal Base Sequence Chromosome Mapping Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Extremities embryology Gene Expression Regulation Genes, Homeobox Molecular Sequence Data Repressor Proteins genetics Support, Non-U.S. Gov't FBrf0123046 20069325 10601017 2000 01 27 2000 01 27 2000 12 18

0261-4189 18 24 1999 Dec 15 Recruitment of the protein tyrosine phosphatase CSW by DOS is an essential step during signaling by the sevenless receptor tyrosine kinase. 6950-61 The pleckstrin homology (PH) domain-containing protein Daughter of Sevenless (DOS) is an essential component of the Sevenless receptor tyrosine kinase (SEV) signaling cascade, which specifies R7 photoreceptor development in the Drosophila eye. Previous results have suggested that DOS becomes tyrosine phosphorylated during SEV signaling and collaborates with the protein tyrosine phosphatase CSW. We have investigated this possibility by identifying tyrosine residues 801 and 854 of DOS as the phosphorylated binding sites for the CSW SH2 domains. We show that these sites become phosphorylated in response to SEV activation and that phosphorylation of both sites is required to allow CSW to bind DOS. Mutant DOS proteins in which either Y801 or Y854 of DOS has been changed to phenylalanine are unable to function during signaling by SEV and other receptor tyrosine kinases. In contrast, we find that a mutant DOS protein in which all tyrosine phosphorylation sites except Y801 and Y854 have been removed is able effectively to provide DOS function during SEV signaling and to rescue the lethality associated with dos loss-of-function mutations. These results indicate that a primary role for DOS during signaling by SEV and other receptor tyrosine kinases is to become phosphorylated at Y801 and Y854 and then recruit CSW. Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA. Herbst R R Zhang X X Qin J J Simon M A MA eng RO1EY9845 EY NEI Journal Article

ENGLAND EMBO J 8208664 0 Eye Proteins 0 Membrane Glycoproteins 0 Recombinant Proteins 0 daughter of sevenless protein 0 sevenless protein EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 3.1.3.- corkscrew protein EC 3.1.3.48 Protein-Tyrosine-Phosphatase IM Amino Acid Sequence Animal Binding Sites Cell Line Drosophila melanogaster genetics physiology Eye Proteins chemistry genetics metabolism Female Heterozygote Male Membrane Glycoproteins metabolism Microscopy, Electron, Scanning Molecular Sequence Data Phosphorylation Photoreceptors, Invertebrate physiology ultrastructure Protein-Tyrosine-Phosphatase metabolism Receptor Protein-Tyrosine Kinases metabolism Recombinant Proteins chemistry metabolism Signal Transduction physiology Spectrum Analysis, Mass Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection src Homology Domains FBrf0057887 93161415 8381718 1993 03 16 1993 03 16 2000 12 18

0092-8674 72 3 1993 Feb 12 A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila. 407-14 D-raf, a Drosophila homolog of Raf-1, plays key roles in multiple signal transduction pathways. Dsor1, a putative factor downstream of D-raf, was genetically identified by screening of dominant suppressors of D-raf. Dsor1Su1 mapped on X chromosome significantly suppressed the D-raf mutant phenotypes, and the loss-of-function mutations of Dsor1 showed phenotypes similar to those of the D-raf null mutations. Dsor1Su1 also significantly suppressed the mutations of other terminal class genes acting further upstream of D-raf. Molecular cloning of Dsor1 revealed its product with striking similarity to the microtubule-associated protein (MAP) kinase activator and yeast PBS2, STE7, and byr1. Our genetic results demonstrate the connection between raf and the highly conserved protein kinase cascade involving MAP kinase in vivo. Laboratory of Experimental Radiology, Aichi Cancer Center Research Institute, Nagoya, Japan. Tsuda L L Inoue Y H YH Yoo M A MA Mizuno M M Hata M M Lim Y M YM Adachi-Yamada T T Ryo H H Masamune Y Y Nishida Y Y eng GENBANK D13782 Journal Article

UNITED STATES Cell 0413066 0 Proto-Oncogene Proteins EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM D-raf Dsor1 MEK Amino Acid Sequence Animal Ca(2+)-Calmodulin Dependent Protein Kinase Cell Division Cloning, Molecular Drosophila melanogaster physiology Gene Expression Genetic Complementation Test Molecular Sequence Data Phosphorylation Protein Kinases genetics Protein-Serine-Threonine Kinases genetics metabolism Proto-Oncogene Proteins physiology Proto-Oncogene Proteins c-raf Signal Transduction Support, Non-U.S. Gov't FBrf0139680 21518593 11606538 2001 10 18 2002 01 15

0016-6731 159 2 2001 Oct Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis. 609-22 Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype. Department of Biology, Whitman College, Walla Walla, Washington 99362, USA. schnorr@pacificu.edu Schnorr J D JD Holdcraft R R Chevalier B B Berg C A CA eng GM-45248 GM NIGMS Journal Article

United States Genetics 0374636 0 DNA Primers 0 DNA Transposable Elements EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 3.6.1.- ras Proteins IM Animal Base Sequence Body Patterning DNA Primers DNA Transposable Elements Drosophila melanogaster genetics growth & development metabolism Enhancer Elements (Genetics) Morphogenesis Mutation Receptor, Epidermal Growth Factor genetics Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. ras Proteins genetics metabolism FBrf0090450 97108744 8951065 1997 01 23 1997 01 23 2002 12 26

0950-1991 122 11 1996 Nov Neither the homeodomain nor the activation domain of Bicoid is specifically required for its down-regulation by the Torso receptor tyrosine kinase cascade. 3499-508 Bicoid (Bcd) is a maternal morphogen responsible for patterning the head and thorax of the Drosophila embryo. Correct specification of head structure, however, requires the activity of the Torso receptor tyrosine kinase cascade, which also represses expression of Bcd targets at the most anterior tip of the embryo. Here, we investigate the role of both the homeodomain (HD) and the activation domain of Bcd in the anterior repression of its targets. When a Bcd mutant protein whose HD has been replaced by the Gal4 DNA-binding domain is expressed in early embryos, a reporter gene driven by Gal4 DNA-binding sites is first activated in an anterior domain and then repressed from the anterior pole. The down-regulation of Bcd-Gal4 activity requires torso function but does not depend on endogenous bcd activity, indicating that the Bcd protein alone and none of its targets is required to mediate the effect of torso. Functional analysis of a chimeric protein, whose activation domain has been replaced by a generic activation domain, indicates that the activation domain of Bcd is also not specifically required for its down-regulation by Torso. We propose that Torso does not affect the ability of Bcd to bind DNA, but instead directs modification of Bcd or of a potential Bcd co-factor, which renders the Bcd protein unable to activate transcription. Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA. Bellaïche Y Y Bandyopadhyay R R Desplan C C Dostatni N N eng Journal Article

ENGLAND Development 8701744 0 Chimeric Proteins 0 DNA-Binding Proteins 0 Insect Hormones 0 bicoid protein, Drosophila EC 2.7.1.- TOR protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM Animal Binding, Competitive Body Patterning Chimeric Proteins DNA-Binding Proteins metabolism Down-Regulation Drosophila melanogaster embryology genetics Female Gene Expression Regulation, Developmental Head embryology Insect Hormones chemistry physiology Receptor Protein-Tyrosine Kinases physiology Signal Transduction Structure-Activity Relationship Support, Non-U.S. Gov't Transcription, Genetic FBrf0064498 94073970 8252627 1994 01 10 1994 01 10 2000 12 18

0092-8674 75 5 1993 Dec 3 The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. 913-26 Development of the Drosophila retina occurs asynchronously; differentiation, its front marked by the morphogenetic furrow, progresses across the eye disc epithelium over a 2 day period. We have investigated the mechanism by which this front advances, and our results suggest that developing retinal cells drive the progression of morphogenesis utilizing the products of the hedgehog (hh) and decapentaplegic (dpp) genes. Analysis of hh and dpp genetic mosaics indicates that the products of these genes act as diffusible signals in this process. Expression of dpp in the morphogenetic furrow is closely correlated with the progression of the furrow under a variety of conditions. We show that hh, synthesized by differentiating cells, induces the expression of dpp, which appears to be a primary mediator of furrow movement. San Francisco General Hospital, University of California 94110. Heberlein U U Wolff T T Rubin G M GM eng Journal Article

UNITED STATES Cell 0413066 0 Insect Hormones 0 Proteins 0 RNA, Messenger 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Cell Differentiation Drosophila melanogaster embryology Eye embryology Gene Expression Genes, Structural, Insect Insect Hormones physiology Morphogenesis Mosaicism Photoreceptors, Invertebrate embryology Proteins physiology RNA, Messenger genetics Retina embryology Transforming Growth Factor beta physiology FBrf0141439 21553064 11696332 2001 11 06 2002 01 22

0960-9822 11 21 2001 Oct 30 The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila. 1716-21 Dbp5 is the only member of the DExH/D box family of RNA helicases that is directly implicated in the export of messenger RNAs from the nucleus of yeast and vertebrate cells. Dbp5 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore complex (NPC). In an attempt to identify proteins present in a highly enriched NPC fraction, two other helicases were detected: RNA helicase A (RHA) and UAP56. This suggested a role for these proteins in nuclear transport. Contrary to expectation, we show that the Drosophila homolog of Dbp5 is not essential for mRNA export in cultured Schneider cells. In contrast, depletion of HEL, the Drosophila homolog of UAP56, inhibits growth and results in a robust accumulation of polyadenylated RNAs within the nucleus. Consequently, incorporation of [35S]methionine into newly synthesized proteins is inhibited. This inhibition affects the expression of both heat-shock and non-heat-shock mRNAs, as well as intron-containing and intronless mRNAs. In HeLa nuclear extracts, UAP56 preferentially, but not exclusively, associates with spliced mRNAs carrying the exon junction complex (EJC). We conclude that HEL is essential for the export of bulk mRNA in Drosophila. The association of human UAP56 with spliced mRNAs suggests that this protein might provide a functional link between splicing and export. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Gatfield D D Le Hir H H Schmitt C C Braun I C IC Köcher T T Wilm M M Izaurralde E E eng Journal Article

England Curr Biol 9107782 0 DNA, Complementary 0 Drosophila Proteins 0 RNA, Antisense 0 RNA, Messenger 0 RNAI gene product EC 2.7.7.- Hel protein, Drosophila EC 2.7.7.- RNA Helicases EC 3.6.1.- RNA-dependent ATPase EC 3.6.1.3 Adenosinetriphosphatase IM Active Transport, Cell Nucleus Adenosinetriphosphatase genetics metabolism Animal Cell Nucleus metabolism Cells, Cultured Cloning, Molecular DNA, Complementary Drosophila Proteins metabolism Drosophila melanogaster Heat-Shock Response Hela Cells Human RNA Helicases genetics metabolism RNA Splicing RNA, Antisense RNA, Messenger metabolism Support, Non-U.S. Gov't Translation, Genetic FBrf0132358 21015574 11131516 2000 12 22 2001 03 01

0074-7696 203 2001 Assembly of the Drosophila germ plasm. 187-213 The Drosophila melanogaster germ plasm has become the paradigm for understanding both the assembly of a specific cytoplasmic localization during oogenesis and its function. The posterior ooplasm is necessary and sufficient for the induction of germ cells. For its assembly, localization of gurken mRNA and its translation at the posterior pole of early oogenic stages is essential for establishing the posterior pole of the oocyte. Subsequently, oskar mRNA becomes localized to the posterior pole where its translation leads to the assembly of a functional germ plasm. Many gene products are required for producing the posterior polar plasm, but only oskar, tudor, valois, germcell-less and some noncoding RNAs are required for germ cell formation. A key feature of germ cell formation is the precocious segregation of germ cells, which isolates the primordial germ cells from mRNA turnover, new transcription, and continued cell division. nanos is critical for maintaining the transcription quiescent state and it is required to prevent transcription of Sex-lethal in pole cells. In spite of the large body of information about the formation and function of the Drosophila germ plasm, we still do not know what specifically is required to cause the pole cells to be germ cells. A series of unanswered problems is discussed in this chapter. Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA. Mahowald A P AP eng Journal Article Review Review, Academic

United States Int Rev Cytol 2985180R IM Animal Body Patterning genetics Cytoplasm genetics metabolism Drosophila embryology genetics ultrastructure Female Gene Expression Regulation, Developmental genetics Germ Cells growth & development metabolism ultrastructure Oocytes growth & development metabolism ultrastructure Oogenesis genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 111 FBrf0064551 94059765 8240970 1994 01 05 1994 01 05 2000 12 18

0925-4773 43 1 1993 Sep Regulation of runt transcription by Drosophila segmentation genes. 3-19 The runt gene plays an important role in the genetic hierarchy that generates the segmented body pattern during the early stages of Drosophila embryogenesis. We studied mRNA expression in mutant embryos in order to investigate the regulation of runt transcription during these stages. We used sensitive whole-mount in situ hybridization procedures to identify the earliest, and therefore most likely direct regulatory effects. There are several distinct phases of runt expression in the early embryo. We find that each phase depends on a different set of regulators. The first phase of expression is a broad-field of mRNA accumulation in the central regions of syncytial blastoderm stage embryos. This pattern is due to terminal repression by the anterior and terminal maternal systems. The effect of the terminal system, even at this early stage, is mediated by two zygotic gap genes, tailless and huckebein. A 7 stripe pattern of runt mRNA accumulation emerges during the process of cellularization. The initial formation of this pattern depends on position-specific repression by zygotic gap genes. Examination of the early RNA patterns of the pair-rule genes even-skipped, hairy, and fushi tarazu indicate that they are also regulated in a similar manner. Three pair-rule genes, hairy, even-skipped, and runt itself, also affect runt's 7 stripe pattern. The effects of runt are stripe specific; the effects of hairy are more uniform; and the patterns obtained in even-skipped mutant embryos show a combination of both stripe specific and uniform regulatory effects. A third distinct phase of expression occurs at the onset of gastrulation when runt becomes expressed in 14 stripes. fushi tarazu plays a negative regulatory role in generating this pattern, whereas the pair-rule genes paired and odd-paired are required for activating or maintaining runt expression during these stages. Department of Biochemistry and Cell Biology, State University of New York at Stony Brook 11794. Klingler M M Gergen J P JP eng Journal Article

IRELAND Mech Dev 9101218 0 DNA-Binding Proteins 0 RNA, Messenger 0 Runt protein IM bcd ems en eve ftz gt hb hkb kni kr odd opa osk otd prd slp tll tsl Alleles Animal DNA-Binding Proteins genetics physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian growth & development metabolism ultrastructure Gene Expression Regulation Genes, Insect Genes, Regulator Genes, Structural, Insect In Situ Hybridization Morphogenesis genetics RNA, Messenger analysis genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Zygote metabolism FBrf0054329 91340748 1908463 1991 09 26 1991 09 26 2002 11 01

0021-9258 266 24 1991 Aug 25 Inactivation of mRNA cap-binding protein complex in Drosophila melanogaster embryos under heat shock. 16007-14 We have studied the role of Drosophila 35-kDa cap-binding protein (CBP) and CBP complex in the mechanism of messenger RNA discrimination established in heat-shocked Drosophila embryos. Drosophila 35-kDa CBP is functionally equivalent to the mammalian eucaryotic initiation factor (eIF)-4E and CBP complex, which includes eIF-4E, might be the counterpart of mammalian eIF-4F. By using anti-eIF-4E antibodies, we found that although translation of the bulk of normal messengers in Drosophila lysates was very dependent on eIF-4E, the mRNAs for the heat shock proteins (hsps) (particularly hsp70 mRNA and with the exception of hsp83 mRNA) were translated almost independently of this factor, suggesting that they may have unstructured leaders. Accordingly, hsp70 mRNA and, to a lesser extent, the mRNAs for the small hsps were found to be more resistant to inhibition by K+ than normal and hsp83 mRNAs. Moreover, Drosophila CBP complex was able to rescue partial but specifically the synthesis of normal proteins when added to a lysate from heat-shocked embryos. However, no significant effect was obtained by Drosophila eIF-4E or eIF-2. Consistent with these results, we found a great decrease in the amount of the CBP complex purified from heat-shocked embryos as compared with normal ones, whereas the amounts of free eIF-4E purified from either source were similar. Together, the above results suggest that some modification leading to the disruption of Drosophila CBP complex may account, at least to some extent, for the mRNA discrimination established in heat-shocked Drosophila embryos. Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas, Madrid, Spain. Zapata J M JM Maroto F G FG Sierra J M JM eng Journal Article

UNITED STATES J Biol Chem 2985121R 0 Carrier Proteins 0 Eukaryotic Initiation Factor-4E 0 Peptide Initiation Factors 0 RNA Cap-Binding Proteins 0 RNA, Messenger 7440-09-7 Potassium 9004-22-2 Globins IM Animal Carrier Proteins genetics metabolism Drosophila melanogaster embryology metabolism Electrophoresis, Polyacrylamide Gel Eukaryotic Initiation Factor-4E Globins genetics Heat Peptide Initiation Factors metabolism Potassium metabolism RNA Cap-Binding Proteins RNA, Messenger metabolism Support, Non-U.S. Gov't Translation, Genetic FBrf0132297 21067892 11152631 2001 01 26 2001 03 15

0950-1991 128 3 2001 Feb Jing: a downstream target of slbo required for developmental control of border cell migration. 321-30 Epithelial to mesenchymal transitions and cell migration are important features of embryonic development and tumor metastasis. We are employing a systematic genetic approach to study the border cells in the Drosophila ovary, as a simple model for these cellular behaviors. Previously we found that expression of the basic-region/leucine zipper transcription factor, C/EBP, is required for the border cells to initiate their migration. Here we report the identification of a second nuclear factor, named JING (which means 'still'), that is required for initiation of border cell migration. The jing locus was identified in a screen for mutations that cause border cell migration defects in mosaic clones. The jing mutant phenotype resembles that of slbo mutations, which disrupt the Drosophila C/EBP gene, but is distinct from other classes of border cell migration mutants. Expression of a jing-lacZ reporter in border cells requires C/EBP. Moreover, expression of jing from a heat-inducible promoter rescues the border cell migration defects of hypomorphic slbo mutants. The JING protein is most closely related to a mouse protein, AEBP2, which was identified on the basis of its ability to bind a small regulatory sequence within the adipocyte AP2 gene to which mammalian C/EBP also binds. We propose that the need to coordinate cell differentiation with nutritional status may be the link between mammalian adipocytes and Drosophila border cells that led to the conservation of C/EBP and AEBP2. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA. Liu Y Y Montell D J DJ eng Journal Article

England Development 8701744 0 AEBP2 protein 0 CCAAT-Enhancer-Binding Proteins 0 Cadherins 0 JING protein 0 Nuclear Proteins 0 RNA, Messenger 0 Repressor Proteins 0 Transcription Factors 148997-45-9 slow border cells protein IM Adipocytes cytology Amino Acid Sequence Animal CCAAT-Enhancer-Binding Proteins genetics metabolism Cadherins genetics metabolism Cell Differentiation Cell Movement Cloning, Molecular Drosophila melanogaster cytology embryology genetics Female Gene Expression Regulation, Developmental Genes, Reporter Immunohistochemistry Molecular Sequence Data Mutation Nuclear Proteins chemistry genetics metabolism Phenotype Physical Chromosome Mapping RNA, Messenger genetics metabolism Repressor Proteins chemistry metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't Transcription Factors chemistry genetics metabolism FBrf0040466 84259319 6430564 1984 08 24 1984 08 24 2000 12 18

0092-8674 37 3 1984 Jul The Drosophila ras oncogenes: structure and nucleotide sequence. 1027-33 Three Drosophila genes homologous to the Ha-ras probe were isolated and mapped to positions 85D, 64B, and 62B on chromosome 3. Two of these genes (termed Dras 1 and Dras 2) were sequenced. In the case of Dras 1, which contains multiple introns, a cDNA clone was isolated and sequenced. In the case of Dras2, the nucleotide sequence fo the genomic clone was determined. Each gene codes for a protein with a predicted molecular weight of 21.6 kd. Alignment of the amino acid sequence of Dras 1 with the vertebrate Ha-ras protein shows that at the amino terminus and central portion (residues 1-121 and 137-164) the two proteins are remarkably similar, and have an overall homology of 75%. The Dras 2 gene lacks significant homology to the vertebrate counterpart at the extreme amino terminus and is homologous only between positions 28-120 and 139-161 (overall homology of 50%). This result suggests that the N terminus of p21 forms a distinct regulatory or functional domain. At the carboxy terminus, the major region of variability among the vertebrate ras proteins, the two Drosophila sequences also display considerable variability. However, both appear to be more similar to exon 4B of the Ki-ras gene. Neuman-Silberberg F S FS Schejter E E Hoffmann F M FM Shilo B Z BZ eng GENBANK K01960 K01961 K01962 Journal Article

UNITED STATES Cell 0413066 IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping Comparative Study Drosophila melanogaster genetics Oncogenes Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0134642 21076514 11204979 2001 02 06 2001 02 22

0016-6723 76 3 2000 Dec Estimation of microsatellite mutation rates in Drosophila melanogaster. 323-6 Microsatellite mutations were studied in a set of 175 mutation accumulation lines, all of them independently derived from a completely homozygous population of Drosophila melanogaster and maintained under strong inbreeding during 80 generations. We assayed 28 microsatellites and detected two mutations. One mutation consisted of a single addition of a dinucleotide repeat and the other was a deletion of five trinucleotide repeats. The average mutation rate was 5.1 x 10(-6), in full agreement with previous estimates from two different sets of mutation accumulation lines. Area de Genética, Departamento de Biología Funcional, Universidad de Oviedo, 33071 Oviedo, Spain. Fernando Vázquez J J Pérez T T Albornoz J J Domínguez A A eng Journal Article

England Genet Res 0370741 0 Plasmids 9007-49-2 DNA IM Animal Base Sequence DNA analysis Drosophila melanogaster genetics Microsatellite Repeats genetics Mutation genetics Plasmids Polymerase Chain Reaction Support, Non-U.S. Gov't FBrf0027524 76118633 814038 1976 04 29 1976 04 29

0016-6731 81 4 1975 Dec Genetic analysis of the proximal region of chromosome 2 of Drosophila melanogaster. I. Detachment products of compound autosomes. 705-21 To examine the genetic composition of proximal heterochromatin in chromosome 2, the detachment of compound second autosomes, for generating proximal deficiencies, appeared a promising method. Compound seconds were detached by gamma radiation. A fraction of the detachment products were recessive lethals owing to proximal deficiencies. Analysis by inter se complementation, pseudo-dominance tests with proximal mutations and allelism tests with known deficiencies provided evidence for at least two loci between the centromere and the light locus in 2L and one locus in 2R between the rolled locus and the centromere. The data further demonstrate that rolled, and probably light, are located within the proximal heterochromatin. Thus, functional genetic loci are found in heterochromatin, albeit at low density. Hilliker A J AJ Holm D G DG eng Journal Article

UNITED STATES Genetics 0374636 0 Heterochromatin IM Alleles Animal Chromosome Mapping Chromosomes radiation effects Drosophila melanogaster Gamma Rays Genes, Lethal Genes, Recessive Heterochromatin radiation effects Mutation Radiation Genetics FBrf0151926 22211539 12223409 2002 09 11 2002 11 08 2003 03 28

0950-1991 129 19 2002 Oct Signaling from germ cells mediated by the rhomboid homolog stet organizes encapsulation by somatic support cells. 4523-34 Germ cells normally differentiate in the context of encapsulating somatic cells. However, the mechanisms that set up the special relationship between germ cells and somatic support cells and the signals that mediate the crucial communications between the two cell types are poorly understood. We show that interactions between germ cells and somatic support cells in Drosophila depend on wild-type function of the stet gene. In males, stet acts in germ cells to allow their encapsulation by somatic cyst cells and is required for germ cell differentiation. In females, stet function allows inner sheath cells to enclose early germ cells correctly at the tip of the germarium. stet encodes a homolog of rhomboid, a component of the epidermal growth factor receptor signaling pathway involved in ligand activation in the signaling cell. The stet mutant phenotype suggests that stet facilitates signaling from germ cells to the epidermal growth factor receptor on somatic cells, resulting in the encapsulation of germ cells by somatic support cells. The micro-environment provided by the surrounding somatic cells may, in turn, regulate differentiation of the germ cells they enclose. Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5329, USA. Schulz Cordula C Wood Cricket G CG Jones D Leanne DL Tazuke Salli I SI Fuller Margaret T MT eng DK 53074 DK NIDDK HD 07493 HD NICHD Journal Article

England Development 8701744 0 Biological Markers 0 Drosophila Proteins 0 Eye Proteins 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 Receptors, Invertebrate Peptide 0 Rho protein, Drosophila 0 epidermal growth factor receptor homolog, Drosophila 0 escargot protein, Drosophila 0 eyes absent protein, Drosophila 0 patched protein, Drosophila 0 rho-2 protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Biological Markers Cell Differentiation Drosophila Proteins genetics metabolism Drosophila melanogaster genetics metabolism Eye Proteins genetics Female Male Membrane Proteins genetics Ovum cytology metabolism physiology Proto-Oncogene Proteins genetics Receptor, Epidermal Growth Factor metabolism Receptors, Invertebrate Peptide metabolism Signal Transduction Spermatozoa cytology metabolism physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0105423 99029842 9814705 1998 12 07 1998 12 07 2000 12 18

0092-8674 95 3 1998 Oct 30 CNK, a RAF-binding multidomain protein required for RAS signaling. 343-53 Kinase suppressor of ras (ksr) is required for efficient signal transmission within the RAS/MAPK cascade. A screen for mutations that modify a ksr-dependent phenotype identified a novel gene, connector enhancer of ksr (cnk), that functions upstream or in parallel to RAF in the RAS pathway. cnk encodes a protein containing several protein-protein interaction domains, suggesting that it brings different signaling molecules together. CNK is required in multiple receptor tyrosine kinase pathways where it appears to be a tyrosine phosphorylation target. Finally, CNK physically interacts with RAF and appears to localize to cell-cell contact regions. Together, these findings suggest that CNK is a novel component of a RAS-dependent signaling pathway that regulates RAF function and/or targets RAF to a specific subcellular compartment upon RAS activation. Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA. Therrien M M Wong A M AM Rubin G M GM eng GENBANK AF100152 AF100153 Journal Article

UNITED STATES Cell 0413066 0 CNK protein 0 Carrier Proteins 0 Insect Proteins EC 2.7.1.- KSR-1 protein kinase EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 3.6.1.- ras Proteins IM Amino Acid Sequence Animal Carrier Proteins chemistry genetics metabolism Cell Differentiation Cell Line Cell Survival Drosophila melanogaster genetics growth & development metabolism Evolution, Molecular Eye chemistry growth & development Genes, Dominant Genes, Suppressor Human Insect Proteins chemistry genetics metabolism Intercellular Junctions metabolism Molecular Sequence Data Mutagenesis Phenotype Phosphorylation Protein Kinases genetics Proto-Oncogene Proteins c-raf metabolism Receptor Protein-Tyrosine Kinases metabolism Signal Transduction Support, Non-U.S. Gov't Wing growth & development ras Proteins antagonists & inhibitors metabolism FBrf0132332 21066151 11139506 2001 01 26 2001 03 15

0016-6731 157 1 2001 Jan Inferring parameters of mutation, selection and demography from patterns of synonymous site evolution in Drosophila. 245-57 Selection acting on codon usage can cause patterns of synonymous evolution to deviate considerably from those expected under neutrality. To investigate the quantitative relationship between parameters of mutation, selection, and demography, and patterns of synonymous site divergence, we have developed a novel combination of population genetic models and likelihood methods of phylogenetic sequence analysis. Comparing 50 orthologous gene pairs from Drosophila melanogaster and D. virilis and 27 from D. melanogaster and D. simulans, we show considerable variation between amino acids and genes in the strength of selection acting on codon usage and find evidence for both long-term and short-term changes in the strength of selection between species. Remarkably, D. melanogaster shows no evidence of current selection on codon usage, while its sister species D. simulans experiences only half the selection pressure for codon usage of their common ancestor. We also find evidence for considerable base asymmetries in the rate of mutation, such that the average synonymous mutation rate is 20-30% higher than in noncoding regions. A Bayesian approach is adopted to investigate how accounting for selection on codon usage influences estimates of the parameters of mutation. Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom. g.mcvean@ed.ac.uk McVean G A GA Vieira J J eng Journal Article

United States Genetics 0374636 0 Codon IM Animal Base Composition Codon genetics Drosophila genetics Drosophila melanogaster genetics Evolution, Molecular Gene Frequency Genes, Insect Genetics, Population Likelihood Functions Models, Genetic Mutation Selection (Genetics) Support, Non-U.S. Gov't FBrf0129727 20411174 10952896 2000 11 15 2000 11 15

0950-1991 127 18 2000 Sep P element homing to the Drosophila bithorax complex. 3981-92 P elements containing a 7 kb DNA fragment from the middle of the Drosophila bithorax complex insert preferentially into the bithorax complex or into the adjacent chromosome regions. This 'homing' property is similar to that reported for the engrailed promoter (Hama, C., Ali, Z. and Kornberg, T. B. (1990) Genes Dev. 4, 1079-1093). The 7 kb fragment does not contain any known promoter, but it acts as a boundary element separating adjacent segmental domains. An enhancer-trap P element was constructed with the homing fragment and the selectable marker flanked by FRT sites. P insertions can be trimmed down by Flp-mediated recombination to just the lacZ reporter, so that the (beta)-galactosidase pattern is not influenced by sequences inside the P element. Twenty insertions into the bithorax complex express (beta)-galactosidase in segmentally limited patterns, reflecting the segmental domains of the bithorax complex where the elements reside. The mapping of segmental domains has now been revised, with enlargement of the abx/bx, bxd/pbx, and the iab-3 domains. The FRT sites in the P elements permit recombination between pairs of elements on opposite chromosomes, to generate duplications or deletions of the DNA between the two insertion sites. Using this technique, the length of the Ultrabithorax transcription unit was varied from 37 to 138 kb, but there was surprisingly little effect on Ultrabithorax function. BCMP Department, Harvard Medical School, Boston, MA 02115, USA. Bender W W Hudson A A eng Journal Article

ENGLAND Development 8701744 0 DNA Transposable Elements 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 RNA, Messenger 0 ultrabithorax protein EC 2.7.7.- DNA Nucleotidyltransferases EC 2.7.7.- FLP recombinase IM Animal DNA Nucleotidyltransferases metabolism DNA Transposable Elements genetics DNA-Binding Proteins genetics Drosophila melanogaster genetics Gene Expression Regulation Genes, Insect genetics Genes, Reporter genetics Homeodomain Proteins genetics Immunohistochemistry Mutation genetics Phenotype Physical Chromosome Mapping RNA, Messenger analysis genetics Recombination, Genetic genetics Support, U.S. Gov't, P.H.S. FBrf0149094 22045830 12049765 2002 06 06 2003 01 27

0925-4773 115 1-2 2002 Jul An essential function of AP-1 heterodimers in Drosophila development. 35-40 Fos and Jun proteins homo- or heterodimerize to form functional AP-1 transcription factors. Drosophila mutants lacking either Jun or Fos display indistinguishable dorsal open phenotypes, indicating an essential function of both Jun and Fos for embryonic dorsal closure. Here we present experiments to determine the basis for this dual requirement. By combining mutant alleles and transgenes expressing Fos and Jun variants with altered dimerization preferences, fly lines were generated in which only specifically defined dimer variants can form. Phenotypic analysis of these mutants reveals that homodimers of Fos or of Jun cannot replace the function of the heterodimeric complex. This defect is not explained by the lower stability of homodimers as compared to heterodimers, because 'pseudo-homodimers' which are as stable as native Jun-Fos heterodimers cannot substitute for their function. We conclude that Jun and Fos play complementary roles that are both required for signal transduction and gene activation during dorsal closure. Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. laura.ciapponi@uniroma1.it Ciapponi Laura L Bohmann Dirk D eng Journal Article

Ireland Mech Dev 9101218 0 Drosophila Proteins 0 Proto-Oncogene Proteins c-jun 0 Transcription Factor AP-1 0 fos protein, Drosophila IM Animal Animals, Genetically Modified Dimerization Drosophila Proteins genetics physiology Drosophila melanogaster embryology physiology Leucine Zippers Proto-Oncogene Proteins c-jun genetics physiology Support, Non-U.S. Gov't Transcription Factor AP-1 genetics physiology FBrf0058571 93202474 8095914 1993 04 22 1993 04 22 2002 11 08

0016-6731 133 3 1993 Mar Tumorous-head (tuh-1; tuh-3) modulates Abd-B bithorax-complex functions in Drosophila melanogaster. 593-604 Abdominal-B (Abd-B) mutants of the bithorax-complex (BX-C) were studied in trans with tuh-3 to evaluate their interactions with this homeotic mutant and the maternal effect locus (tuh-1) controlling tuh-3 expression. Head defects occur in tuh-3 offspring from tuh-1h homozygous mothers, while genital defects occur in homozygous tuh-3 offspring from mothers carrying the tuh-1g allele. The influence exerted by the tuh-1 maternal effects on tuh-3 Abd-B transcript distribution was evaluated by whole mount in situ hybridization. Results demonstrated that: (1) of the 21 Abd-B mutants tested, head defects were produced by SGA62, I127B, I127O and tuh-3, with I127B and tuh-3 as the only mutants to require the head defect maternal effect for expression; (2) one specific cluster of regulatory (r) mutants, Uab1, 65 and I127B, enhanced penetrance and expressivity of tuh-3 head defects; (3) the most profound suppression of head defect penetrance occurred when Abd-B mutants eliminated the morphogenetic (m) and r functions; (4) genital defects increased in frequency in tuh-3/Abd-B mutant trans-heterozygotes with loss of r function; (5) Abd-B transcription (class A, class B, class C) appears normal in tuh-3 embryos when their mothers pass on the tuh-1h head defect maternal effect, whereas the regulatory transcripts (class B and class C) are reduced when tuh-3 mothers pass on the tuh-1g genital disc maternal effect; (5) tuh eye-antennal imaginal discs express ABD-B protein; and (6) tuh-3 misregulates both m and r function of Abd-B. Department of Biology, University of Central Florida, Orlando 32816. Kuhn D T DT Mack J A JA Duan C C Packert G G eng Journal Article

UNITED STATES Genetics 0374636 0 Abd-B proteins, Drosophila 0 Insect Hormones IM Abd-B tuh-1 tuh-3 Animal Chromosome Mapping Drosophila melanogaster genetics physiology Female Genes, Homeobox Head abnormalities Heterozygote Insect Hormones genetics Male Models, Genetic Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription, Genetic FBrf0138371 21430857 11546743 2001 09 07 2001 10 18 2002 05 20

0950-1991 128 17 2001 Sep msh specifies dorsal cell fate in the Drosophila wing. 3263-8 Drosophila limbs develop from imaginal discs that are subdivided into compartments. Dorsal-ventral subdivision of the wing imaginal disc depends on apterous activity in dorsal cells. Apterous protein is expressed in dorsal cells and is responsible for (1) induction of a signaling center along the dorsal-ventral compartment boundary (2) establishment of a lineage restriction boundary between compartments and (3) specification of dorsal cell fate. Here, we report that the homeobox gene msh (muscle segment homeobox) acts downstream of apterous to confer dorsal identity in wing development. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Milán M M Weihe U U Tiong S S Bender W W Cohen S M SM eng Journal Article

England Development 8701744 0 Homeodomain Proteins 0 Insect Proteins 0 Transcription Factors 0 muscle segment homeobox protein 147756-66-9 apterous protein, Drosophila IM Alleles Animal Body Patterning physiology Cell Differentiation Drosophila melanogaster genetics growth & development Homeodomain Proteins genetics metabolism Insect Proteins genetics metabolism Mutagenesis Signal Transduction physiology Transcription Factors genetics metabolism Wing cytology growth & development FBrf0044483 86301834 3091446 1986 10 15 1986 10 15 2000 12 18

0016-6731 113 4 1986 Aug The question of the total gene number in Drosophila melanogaster. 869-95 A statistical analysis has been carried out on the distribution and allelism of nearly 500 sex-linked, X-ray-induced, cytologically normal and rearranged lethal mutations in Drosophila melanogaster that were obtained by G. Lefevre. The mutations were induced in four different regions of the X chromosome: (1) 1A1-3E8, (2) 6D1-8A5, (3) 9E1-11A7 and (4) 19A1-20F4, which together comprise more than one-third of the entire chromosome.--The analysis shows that the number of alleles found at different loci does not fit a Poisson distribution, even when the proper procedures are taken to accommodate the truncated nature of the data. However, the allele distribution fits a truncated negative binomial distribution quite well, with cytologically normal mutations fitting better than rearrangement mutations. This indicates that genes are not equimutable, as required for the data to fit a Poisson distribution.--Using the negative binomial parameters to estimate the number of genes that did not produce a detectable lethal mutation in our experiment (n0) gave a larger number than that derived from the use of the Poisson parameter. Unfortunately, we cannot estimate the total numbers of nonvital loci, loci with undetectable phenotypes and loci having extremely low mutabilities. In any event, our estimate of the total vital gene number was far short of the total number of bands in the analyzed regions; yet, in several short intervals, we have found more vital genes than bands; in other intervals, fewer. We conclude that the one-band, one-gene hypothesis, in its literal sense, is not true; furthermore, it is difficult to support, even approximately.--The question of the total gene number in Drosophila will, not doubt, eventually be solved by molecular analyses, not by statistical analysis of mutation data or saturation studies. Lefevre G G Watkins W W eng GM-13631 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Chromosome Mapping Drosophila melanogaster genetics Genes radiation effects Genes, Lethal Mathematics Models, Genetic Mutation Support, U.S. Gov't, P.H.S. X Chromosome FBrf0125416 20115421 10648226 2000 03 17 2000 03 17 2002 11 01

0950-1991 127 4 2000 Feb Structure, function and evolution of sex-determining systems in Dipteran insects. 667-77 Nature has evolved an astonishing variety of genetic and epigenetic sex-determining systems which all achieve the same result, the generation of two sexes. Genetic and molecular analyses, mainly performed during the last 20 years, have gradually revealed the mechanisms that govern sexual differentiation in a few model organisms. In this review, we will introduce the sex-determining system of Drosophila and compare the fruitfly to the housefly Musca domestica and other Dipteran insects. Despite the ostensible variety, all these insects use the same basic strategy: a primary genetic signal that is different in males and females, a key gene that responds to the primary signal, and a double-switch gene that eventually selects between two alternative sexual programmes. These parallels, however, do not extend to the molecular level. Except for the double-switch gene doublesex at the end of the cascade, no functional homologies were found between more distantly related insects. In particular, Sex-lethal, the key gene that controls sexual differentiation in Drosophila, does not have a sex-determining function in any other genus studied so far. These results show that sex-determining cascades, in comparison to other regulatory pathways, evolve much more rapidly. Zoological Institute, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Schütt C C Nöthiger R R eng Journal Article Review Review, Tutorial

ENGLAND Development 8701744 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Alternative Splicing Animal Comparative Study Diptera genetics growth & development Dosage Compensation (Genetics) Drosophila melanogaster genetics growth & development Evolution Female Genes, Insect Germ Cells Houseflies genetics growth & development Male RNA-Binding Proteins genetics Sex Characteristics Sex Determination (Genetics) Sex Differentiation genetics Signal Transduction Support, Non-U.S. Gov't 93 FBrf0108178 99178998 10077620 1999 05 20 1999 05 20 2000 12 18

0027-8424 96 6 1999 Mar 16 Microsatellite instability in Drosophila spellchecker1 (MutS homolog) mutants. 2964-9 We have cloned a mutS homolog from Drosophila melanogaster called spellchecker1 (spel1) and have constructed spel1 mutant flies. MutS proteins promote the correction of DNA mismatches and serve important roles in DNA replication, recombination, and repair. The spel1 gene belongs to a subfamily of mutS first characterized by the MSH2 gene of yeast and which also includes hMSH2, one of the two major hereditary nonpolyposis colon cancer loci of humans. Like msh2 mutants in other species, we find that flies lacking the spel1 gene suffer a highly increased rate of instability in long runs of dinucleotide repeats when analyzed after 10-12 fly generations. Using a new assay, we have also discovered that mutations in spel1 decrease the stability of a dinucleotide repeat when it is copied into the site of a double-strand break during gene conversion. Contrary to the case in mammalian cells, spel1 deficiency does not affect tolerance of flies to a methylating agent nor does it affect resistance to gamma-irradiation. Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA. Flores C C Engels W W eng GENBANK U17893 GM30948 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Bacterial Proteins 0 MutS protein 0 Recombinant Proteins 0 spel1 protein IM Animal Bacterial Proteins genetics DNA Repair DNA Replication Drosophila melanogaster genetics Genes, Insect Microsatellite Repeats genetics Molecular Sequence Data Mutation Recombinant Proteins genetics Recombination, Genetic Sequence Homology, Nucleic Acid Support, U.S. Gov't, P.H.S. FBrf0037609 82184394 6804094 1982 07 08 1982 07 08 2000 12 18

0092-8674 28 3 1982 Mar Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster. 451-61 The decapentaplegic gene complex (2-4.0) in Drosophila melanogaster is defined by a series of allelic mutations affecting imaginal disk development. Decapentaplegic (dpp) mutant individuals exhibit a variety of pattern deficiencies and duplications in structures derived from one or more of the 15 major imaginal disks. Based on dpp mutant phenotypes, we suggest that the dpp gene complex is involved in the elaboration of positional information within developing epidermal tissue. The dpp mutations are recessive and fall into six phenotypic classes. Milder alleles (classes I and II) affect only one or a few disks while most alleles (classes III, IV, V and EL) affect all major imaginal disks. Class EL homozygotes are embryonic lethals; development is arrested before germ-band shortening late in gastrulation. Presently inseparable from EL, is a haplo-insufficient function (Hin-d) associated with the distal (left) end of the dpp gene complex. The dpp gene complex occupies most or all of 22F1--3, three densely staining polytene chromosome bands. A colinearity exists between map positions of the four identified functional units within the complex and the severities of mutant phenotypes caused by disruption of these functions. Most dpp mutations are gross chromosomal rearrangements; they exert polar effects on the decapentaplegic functions that are proximal to the rearrangement breakpoints in 22F. Many structural similarities exist between the decapentaplegic and bithorax gene complexes. Spencer F A FA Hoffmann F M FM Gelbart W M WM eng Journal Article

UNITED STATES Cell 0413066 0 Mutagens 62-50-0 Ethyl Methanesulfonate IM Alleles Animal Chromosome Mapping Drosophila melanogaster embryology genetics Ethyl Methanesulfonate pharmacology Female Male Morphogenesis Mutagens Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Wing embryology FBrf0093573 97281708 9136016 1997 09 03 1997 09 03 2000 12 18

0016-6731 146 1 1997 May Dominant mutations of Drosophila MAP kinase kinase and their activities in Drosophila and yeast MAP kinase cascades. 263-73 Eight alleles of Dsor1 encoding a Drosophila homologue of mitogen-activated protein (MAP) kinase kinase were obtained as dominant suppressors of the MAP kinase kinase kinase D raf. These Dsor1 alleles themselves showed no obvious phenotypic consequences nor any effect on the viability of the flies, although they were highly sensitive to upstream signals and strongly interacted with gain-of-function mutations of upstream factors. They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER). Furthermore, the Dsor1 alleles showed no significant interaction with gain-of-function mutations of DER. The observed difference in activity of the Dsor1 alleles among the RTK pathways suggests Dsor1 is one of the components of the pathway that regulates signal specificity. Expression of Dsor1 in budding yeast demonstrated that Dsor1 can activate yeast MAP kinase homologues if a proper activator of Dsor1 is coexpressed. Nucleotide sequencing of the Dsor1 mutant genes revealed that most of the mutations are associated with amino acid changes at highly conserved residues in the kinase domain. The results suggest that they function as suppressors due to increased reactivity to upstream factors. Laboratory of Developmental Biology, Graduate School of Science, Nagoya University, Japan. Lim Y M YM Tsuda L L Inoue Y H YH Irie K K Adachi-Yamada T T Hata M M Nishi Y Y Matsumoto K K Nishida Y Y eng Journal Article

UNITED STATES Genetics 0374636 EC 2.7.1.- Dsor1 gene product, D. melanogaster EC 2.7.1.37 Protein Kinases IM Alleles Amino Acid Sequence Animal Drosophila genetics Eye enzymology ultrastructure Genes, Dominant Male Microscopy, Electron Molecular Sequence Data Mutation Protein Kinases chemistry genetics metabolism Saccharomyces cerevisiae genetics Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0051938 90169480 1968411 1990 04 06 1990 04 06 2000 12 18

0016-6731 124 2 1990 Feb Dosage requirements of Ultrabithorax and bithoraxoid in the determination of segment identity in Drosophila melanogaster. 357-66 The wild-type Ultrabithorax (Ubx) and bithoraxoid (bxd) functions are primarily responsible for establishing the identity of parasegment 6 (PS6) in the Drosophila embryo and thus the identity of the posterior compartment of the third thoracic segment (pT3) and the anterior compartment of the first abdominal segment (aA1) in the adult. The experiments described were designed to test the ability of an increased dosage of Ubx+ and bxd+ to affect the transformation of PS5 toward PS6. The results are consistent with the ideas that (1) multiple copies of Ubx+ and bxd+ cause some cells within PS5 to take on the characteristics of PS6 cells but do not cause an overall parasegmental transformation of PS5 toward PS6, (2) cellular identity depends not only on the activity of Ubx+ but on its concentration as well, and (3) that an interaction between Ubx+ and the wild-type Antennapedia (Antp) gene establishes segmental identity in pT2. In the first instar larvae carrying eight copies of Ubx+ and bxd+ the fine hairs of the T3 setal belt are transformed toward the hook-like structures of the A1 setal belt. Other structures within this segment are unaffected. In the adult, the haltere is reduced in size. The transformation of pT2 cells (wing) toward pT3 cells (haltere) is seen in adults carrying eight doses of wild type Ubx and bxd by decreasing the amount of the bithorax complex (BX-C) regulator Polycomb (Pc). However, the transformation of the T3 setal belt is not enhanced in the larvae of these animals. The interaction between the genes of the Antennapedia complex (ANT-C) and the Ubx+ and bxd+ functions in pT2 is dosage sensitive only when the animals carry one copy of Pc. In these animals, the transformation of wing toward haltere is significantly enhanced. Division of Biology, California Institute of Technology, Pasadena. Smolik-Utlaut S M SM eng GM08984 GM NIGMS HD06331 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Animal Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Homeobox Genotype Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0099543 98038745 9372908 1997 12 16 1997 12 16 2001 11 02

0270-7306 17 12 1997 Dec The polycomb group protein complex of Drosophila melanogaster has different compositions at different target genes. 6773-83 In Drosophila the Polycomb group genes are required for the long-term maintenance of the repressed state of many developmental regulatory genes. Their gene products are thought to function in a common multimeric complex that associates with Polycomb group response elements (PREs) in target genes and regulates higher-order chromatin structure. We show that the chromodomain of Polycomb is necessary for protein-protein interactions within a Polycomb-Polyhomeotic complex. In addition, Posterior Sex Combs protein coimmunoprecipitates Polycomb and Polyhomeotic, indicating that they are members of a common multimeric protein complex. Immunoprecipitation experiments using in vivo cross-linked chromatin indicate that these three Polycomb group proteins are associated with identical regulatory elements of the selector gene engrailed in tissue culture cells. Polycomb, Polyhomeotic, and Posterior Sex Combs are, however, differentially distributed on regulatory sequences of the engrailed-related gene invected. This suggests that there may be multiple different Polycomb group protein complexes which function at different target sites. Furthermore, Polyhomeotic and Posterior Sex Combs are also associated with expressed genes. Polyhomeotic and Posterior Sex Combs may participate in a more general transcriptional mechanism that causes modulated gene repression, whereas the inclusion of Polycomb protein in the complex at PREs leads to stable silencing. ZMBH, University of Heidelberg, Germany. Strutt H H Paro R R eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Chromatin 0 Insect Proteins 0 Recombinant Fusion Proteins 0 Repressor Proteins 134549-01-2 Polycomb protein, insect IM Animal Animals, Genetically Modified Binding Sites genetics Chromatin chemistry genetics Chromosome Mapping Drosophila melanogaster chemistry genetics Female Gene Expression Regulation Genes, Insect Insect Proteins chemistry genetics Male Mutation Recombinant Fusion Proteins chemistry genetics Repressor Proteins chemistry genetics Support, Non-U.S. Gov't FBrf0131307 20556145 11102373 2000 12 28 2001 02 15

0016-6731 156 4 2000 Dec A directed mutagenesis screen in Drosophila melanogaster reveals new mutants that influence hedgehog signaling. 1777-85 The Hedgehog signaling pathway has been recognized as essential for patterning processes in development of metazoan animal species. The signaling pathway is, however, not entirely understood. To start to address this problem, we set out to isolate new mutations that influence Hedgehog signaling. We performed a mutagenesis screen for mutations that dominantly suppress Hedgehog overexpression phenotypes in the Drosophila melanogaster wing. We isolated four mutations that influence Hedgehog signaling. These were analyzed in the amenable wing system using genetic and molecular techniques. One of these four mutations affects the stability of the Hedgehog expression domain boundary, also known as the organizer in the developing wing. Another mutation affects a possible Hedgehog autoregulation mechanism, which stabilizes the same boundary. MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom. Haines N N van den Heuvel M M eng Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Insect Proteins 0 Proteins 0 cubitus interruptus protein 0 dpp protein, Drosophila 0 hedgehog protein, vertebrate 149291-21-4 hedgehog protein, Drosophila IM Animal Chromosome Mapping DNA-Binding Proteins genetics physiology Drosophila melanogaster genetics Genes, Structural, Insect Genes, Suppressor Genetic Complementation Test Insect Proteins genetics physiology Morphogenesis genetics Mutagenesis Phenotype Proteins genetics physiology Signal Transduction genetics Support, Non-U.S. Gov't Wing ultrastructure FBrf0111491 99403006 10471712 1999 10 28 1999 10 28 2001 11 28

0016-6731 153 1 1999 Sep A genetic screen for modifiers of E2F in Drosophila melanogaster. 275-87 The activity of the E2F transcription factor is regulated in part by pRB, the protein product of the retinoblastoma tumor suppressor gene. Studies of tumor cells show that the p16(ink4a)/cdk4/cyclin D/pRB pathway is mutated in most forms of cancer, suggesting that the deregulation of E2F, and hence the cell cycle, is a common event in tumorigenesis. Extragenic mutations that enhance or suppress E2F activity are likely to alter cell-cycle control and may play a role in tumorigenesis. We used an E2F overexpression phenotype in the Drosophila eye to screen for modifiers of E2F activity. Coexpression of dE2F and its heterodimeric partner dDP in the fly eye induces S phases and cell death. We isolated 33 enhancer mutations of this phenotype by EMS and X-ray mutagenesis and by screening a deficiency library collection. The majority of these mutations sorted into six complementation groups, five of which have been identified as alleles of brahma (brm), moira (mor) osa, pointed (pnt), and polycephalon (poc). osa, brm, and mor encode proteins with homology to SWI1, SWI2, and SWI3, respectively, suggesting that the activity of a SWI/SNF chromatin-remodeling complex has an important impact on E2F-dependent phenotypes. Mutations in poc also suppress phenotypes caused by p21(CIP1) expression, indicating an important role for polycephalon in cell-cycle control. Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA. Staehling-Hampton K K Ciampa P J PJ Brook A A Dyson N N eng GM-53203 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 RBF protein 0 Transcription Factors 0 retinoblastoma binding protein 1 0 transcription factor DP1 0 transcription factor E2F IM Animal Cell Cycle Cell Death Dimerization Drosophila melanogaster anatomy & histology embryology genetics growth & development Eye growth & development metabolism ultrastructure Genes, Dominant genetics Genes, Insect Genes, cdc genetics physiology Genetic Complementation Test Insect Proteins genetics physiology Microscopy, Electron, Scanning Mutation Phenotype Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic genetics Transcription Factors genetics metabolism FBrf0077250 95024193 7938024 1994 11 23 1994 11 23 2002 11 01

0027-8424 91 22 1994 Oct 25 Sex-specific processing of the Drosophila exuperantia transcript is regulated in male germ cells by the tra-2 gene. 10752-6 The Drosophila exuperantia (exu) gene encodes overlapping sex-specific, germline-dependent mRNAs. In this work, the structural differences between these sex-specific exu mRNAs were determined by sequence analysis of 9 ovary and 10 testis cDNAs. The transformer 2 (tra-2) gene functions in sex determination of female somatic cells through its role in regulating female-specific splicing of doublesex (dsx) RNA. We report here that tra-2 is required in male germ cells for efficient male-specific processing of exu RNA; in the absence of tra-2, X/Y males produce a new mRNA which is processed at its 3' end so that it contains sequences normally specific to the female 3' untranslated region. Although the processing event that requires tra-2 occurs in an untranslated region of the exu transcript, the isolation and characterization of a male-specific exu allele which deletes male 3' untranslated sequence indicate that this processing is biologically significant. Department of Biological Sciences, Columbia University, New York, NY 10027. Hazelrigg T T Tu C C eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Egg Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 Ribonucleoproteins 0 transformer-2 protein 144998-54-9 exuperantia protein, Drosophila IM bcd exu tra-2 Alleles Animal Comparative Study Drosophila melanogaster genetics Egg Proteins biosynthesis Female Gene Expression Regulation Gene Library Homozygote Male Ovary metabolism Phenotype RNA, Messenger biosynthesis RNA-Binding Proteins biosynthesis Ribonucleoproteins biosynthesis genetics Sex Characteristics Spermatozoa metabolism Support, Non-U.S. Gov't Testis metabolism Transcription, Genetic FBrf0104764 98421557 9748152 1998 10 08 1998 10 08 2000 12 18

0036-8075 281 5385 1998 Sep 25 The evolutionary dynamics of sex determination. 1990-4 REVIEW There is substantial cytogenetic data indicating that the process of sex determination can evolve relatively rapidly. However, recent molecular studies on the evolution of the regulatory genes that control sex determination in the insect Drosophila melanogaster, the nematode Caenorhabditis elegans, and mammals suggest that, although certain sex determination regulatory genes have evolved relatively rapidly, other sex determination regulatory genes are quite conserved. Thus, studies of the evolution of sex determination, a process that appears to have elements that undergo substantial evolutionary change and others that may be conserved, could provide substantial insights into the kinds of forces that both drive and constrain the evolution of developmental hierarchies. Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA. Marín I I Baker B S BS eng Journal Article Review Review, Tutorial

UNITED STATES Science 0404511 IM Animal Evolution Female Gene Expression Regulation Male Mutation Selection (Genetics) Sex Chromosomes genetics Sex Determination (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 36 FBrf0100624 98151768 9491068 1998 03 19 1998 03 19 2000 12 18

0026-8925 257 2 1998 Jan Screening of larval/pupal P-element induced lethals on the second chromosome in Drosophila melanogaster: clonal analysis and morphology of imaginal discs. 103-12 We have carried out screens for lethal mutations on the second chromosome of Drosophila melanogaster that are associated with abnormal imaginal disc morphologies, particularly in the wing disc. From a collection of 164 P element-induced mutations with a late larva/pupa lethal phase we have identified 56 new loci whose gene products are required for normal wing disc development and for normal morphology of other larval organs. Genetic mosaics of these 56 mutant lines show clonal mutant phenotypes for 23 cell-viable mutations. These phenotypes result from altered cell parameters. Causal relationships between disc and clonal phenotypes are discussed. Centro de Biología Molecular Severo Ochoa, Madrid, Spain. Roch F F Serras F F Cifuentes F J FJ Corominas M M Alsina B B Amorós M M López-Varea A A Hernández R R Guerra D D Cavicchi S S Baguñá J J García-Bellido A A eng Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA Transposable Elements IM Animal Chromosome Mapping Clone Cells DNA Transposable Elements genetics Drosophila melanogaster genetics growth & development Epithelial Cells pathology Gene Expression Regulation, Developmental Genes, Insect Genes, Lethal Larva Morphogenesis genetics Mosaicism Mutagenesis, Insertional Phenotype Pupa Support, Non-U.S. Gov't Wing abnormalities growth & development FBrf0110176 99298171 10369659 1999 08 19 1999 08 19 2000 12 18

0261-4189 18 12 1999 Jun 15 Gastrulation in Drosophila: the logic and the cellular mechanisms. 3187-92 The egg contains a set of molecules that can be used to trigger cell-shape changes leading to morphogenetic movements. The temporally and spatially controlled activation of these molecules, and hence the choreography of gastrulation movements, is determined by region-specific expression of transcription factors which turn on a set of downstream targets whose products mediate the successive steps of gastrulation. Institut für Genetik, Universität zu Köln, Weyertal 121, D-50931 Köln, Germany. mleptin@uni-koeln.de Leptin M M eng Journal Article Review Review, Tutorial

ENGLAND EMBO J 8208664 IM Animal Body Patterning Cell Size Drosophila melanogaster cytology embryology genetics metabolism Embryo, Nonmammalian physiology Gastrula cytology metabolism physiology Gene Expression Regulation, Developmental Morphogenesis 33 FBrf0141282 21556889 11700298 2001 11 08 2002 01 15

0066-4197 35 2001 Epithelial cell polarity and cell junctions in Drosophila. 747-84 The polarized architecture of epithelial cells and tissues is a fundamental determinant of animal anatomy and physiology. Recent progress made in the genetic and molecular analysis of epithelial polarity and cellular junctions in Drosophila has led to the most detailed understanding of these processes in a whole animal model system to date. Asymmetry of the plasma membrane and the differentiation of membrane domains and cellular junctions are controlled by protein complexes that assemble around transmembrane proteins such as DE-cadherin, Crumbs, and Neurexin IV, or other cytoplasmic protein complexes that associate with the plasma membrane. Much remains to be learned of how these complexes assemble, establish their polarized distribution, and contribute to the asymmetric organization of epithelial cells. Department of Zoology, University of Toronto, 25 Harbord Street, Toronto, Ontario M5S3G5, Canada. utepass@zoo.utoronto.ca Tepass U U Tanentzapf G G Ward R R Fehon R R eng NS34783 NS NINDS Journal Article Review Review, Academic

United States Annu Rev Genet 0117605 IM Animal Cell Polarity physiology Drosophila melanogaster physiology Epithelial Cells physiology Intercellular Junctions physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 192 FBrf0127357 20215009 10750054 2000 05 12 2000 05 12 2000 12 18

0022-104X 288 1 2000 Apr 15 Haplotype dimorphism in a SNP collection from Drosophila melanogaster. 63-75 A moderate resolution single nucleotide polymorphism (SNP) map of the genome of Drosophila melanogaster that is designed for use in quantitative genetic mapping is described. Seventeen approximately 500 nucleotide gene sequences spaced at 10 to 20 centimorgan intervals were combined with 49 shorter sequence tag sites (STSs) at 5 to 10 centimorgan intervals to generate a map that should not leave any gaps greater than one half of a chromosome arm when any two wild type lines are compared. Of 20 markers with sufficient polymorphism to construct haplotype cladograms, 13 showed evidence for two divergent classes of haplotype. The possible mechanisms for and implications of the unexpected finding that two thirds of all short gene sequences in D. melanogaster may be dimorphic are discussed, including the suggestion that admixture between two separate lineages may have been a major event in the history of the species. Department of Biology, University of Michigan, Ann Arbor, Michigan 48109, USA. Teeter K K Naeemuddin M M Gasperini R R Zimmerman E E White K P KP Hoskins R R Gibson G G eng Journal Article

UNITED STATES J Exp Zool 0375365 IM Animal Base Sequence Drosophila melanogaster genetics Genome Haplotypes genetics Molecular Sequence Data Phylogeny Polymorphism, Single Nucleotide genetics Sequence Analysis, DNA Support, Non-U.S. Gov't FBrf0134775 21148771 11254125 2001 03 19 2001 04 12

0026-8925 264 6 2001 Feb Essential genes in proximal 3L heterochromatin of Drosophila melanogaster. 782-9 We have further characterized essential loci within the centric heterochromatin of the left arm of chromosome 3 (3L) of Drosophila melanogaster, using EMS, radiation and P element mutagenesis. We failed to find any new essential genes, a result that suggests a lower-than-average gene density in this region. Mutations affecting expression of the most proximal gene [lethal 1, l1 or l(3)80Fj] act as dominant suppressors of Polycomb (Pc), behavior which is consistent with a putative trithorax group (trx-G) gene. The third gene to the left of the centromere [lethal 3, l3 or l(3)80Fh] is likely to correspond to verthandi (vtd), a known trx-G gene that plays a role in the regulation of hedgehog (hh) expression and signalling. The intervening gene [lethal 2, l2 or l(3)80Fi] is required throughout development, and mutant alleles have interesting phenotypes; in various allelic combinations that survive, we observe fertility, bristle, wing, eye and cuticle defects. Department of Molecular Biology and Biochemistry, Simon Fraser University Burnaby, BC, Canada. Schulze S S Sinclair D A DA Silva E E Fitzpatrick K A KA Singh M M Lloyd V K VK Morin K A KA Kim J J Holm D G DG Kennison J A JA Honda B M BM eng Journal Article

Germany Mol Gen Genet 0125036 0 Genetic Markers 0 Heterochromatin 0 Insect Proteins 0 Repressor Proteins 134549-01-2 Polycomb protein, insect IM Animal Chromosome Mapping Crosses, Genetic Drosophila melanogaster anatomy & histology genetics growth & development Female Genes, Essential Genetic Markers Heterochromatin genetics Insect Proteins genetics Male Mutagenesis, Insertional Phenotype Repressor Proteins genetics Support, Non-U.S. Gov't Suppression, Genetic Wing anatomy & histology FBrf0092665 97225213 9071586 1997 07 24 1997 07 24 2000 12 18

0016-6731 145 2 1997 Feb Nucleotide variation and conservation at the dpp locus, a gene controlling early development in Drosophila. 311-23 A study of polymorphism and species divergence of the dpp gene of Drosophila has been made. Eighteen lines from a population of D. melanogaster were sequenced for 5200 bp of the Hin region of the gene, coding for the dpp polypeptide. A comparison was made with sequence from D. simulans. Ninety-six silent polymorphisms and three amino acid replacement polymorphisms were found. The overall silent polymorphism (0.0247) is low, but haplotype diversity (0.0066 for effectively silent sites and 0.0054 for all sites) is in the range found for enzyme loci. Amino acid variation is absent in the N-terminal signal peptide, the C-terminal TGF-beta peptide and in the N-terminal half of the pro-protein region. At the nucleotide level there is strong conservation in the middle half of the large-intron and in the 3' untranslated sequence of the last exon. The 3' untranslated conservation, which is perfect for 110 bp among all the divergent species, is unexplained. There is strong positive linkage disequilibrium among polymorphic sites, with stretches of apparent gene conversion among originally divergent sequences. The population apparently is a migration mixture of divergent clades. Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA. Richter B B Long M M Lewontin R C RC Nitasaka E E eng GENBANK U63854 GM-21179 GM NIGMS GM-29301 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 dpp protein, Drosophila 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Conserved Sequence DNA Drosophila genetics growth & development Drosophila melanogaster genetics growth & development Genes, Insect Haplotypes Insect Proteins genetics Molecular Sequence Data Phylogeny Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. Variation (Genetics) FBrf0078205 95324395 7600985 1995 08 10 1995 08 10 2000 12 18

0950-1991 121 6 1995 Jun Discrete Polycomb-binding sites in each parasegmental domain of the bithorax complex. 1681-9 The Polycomb protein of Drosophila melanogaster maintains the segmental expression limits of the homeotic genes in the bithorax complex. Polycomb-binding sites within the bithorax complex were mapped by immunostaining of salivary gland polytene chromosomes. Polycomb bound to four DNA fragments, one in each of four successive parasegmental regulatory regions. These fragments correspond exactly to the ones that can maintain segmentally limited expression of a lacZ reporter gene. Thus, Polycomb acts directly on discrete multiple sites in bithorax regulatory DNA. Constructs combining fragments from different regulatory regions demonstrate that Polycomb-dependent maintenance elements can act on multiple pattern initiation elements, and that maintenance elements can work together. The cooperative action of maintenance elements may motivate the linear order of the bithorax complex. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Chiang A A O'Connor M B MB Paro R R Simon J J Bender W W eng Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 Proteins 134549-01-2 Polycomb protein, insect 9007-49-2 DNA IM Animal Chromosome Mapping DNA Drosophila melanogaster embryology genetics Gene Expression Genes, Homeobox Insect Hormones genetics Morphogenesis genetics Proteins genetics Regulatory Sequences, Nucleic Acid Salivary Glands physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0048201 88196843 3129333 1988 06 09 1988 06 09 2000 12 18

0016-6731 118 2 1988 Feb Cytogenetic definition and morphogenetic analysis of Delta, a gene affecting neurogenesis in Drosophila melanogaster. 235-45 We have conducted a genetic analysis of a small interval of the third chromosome known to include Delta (Dl), a locus that affects the segregation of the ectoderm into neural and epidermal lineages during embryogenesis and the morphogenesis of some ectodermally derived structures, in Drosophila melanogaster. This analysis has led to the definition of seven independent complementation groups, one of which is Delta, within the interval extending from 91F6-13 to 92A2. Among the extant mutations in these seven loci, only mutations in Dl lead to the so-called neurogenic phenotype: hypertrophy of the nervous system and reduction of the epidermis. Combined cytogenetic and genetic analyses allow us to define absolute proximal (91F5-92A1) and distal (92A2) cytogenetic limits for the Dl locus. We have isolated hypomorphic and amorphic alleles of Dl and find that, for any given allele, there is an inverse correlation between neural hypertrophy and epidermal reduction in embryos and a direct correlation between the severity of embryonic phenotypes in mutant homozygotes and hemizygotes and the imaginal phenotype in heterozygous adults. Department of Biology, Indiana University, Bloomington 47405. Alton A K AK Fechtel K K Terry A L AL Meikle S B SB Muskavitch M A MA eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Drosophila melanogaster embryology genetics growth & development Ectoderm ultrastructure Mutation Neurons ultrastructure Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0059040 93109300 8417324 1993 01 27 1993 01 27 2000 12 18

0270-7306 13 1 1993 Jan Isolation of RRM-type RNA-binding protein genes and the analysis of their relatedness by using a numerical approach. 174-83 Proteins with RNA recognition motifs (RRMs) have important roles in a great many aspects of RNA metabolism. However, this family has yet to be systematically studied in any single organism. In order to investigate the size of the RRM gene family in Drosophila melanogaster and to clone members of this family, we used a polymerase chain reaction (PCR) with highly degenerate oligonucleotides to amplify DNA fragments between the RNP-1 and RNP-2 consensus sequences of the RRM proteins. Cloning and sequencing of 124 PCR products revealed 12 different RRM sequences (RRM1 to RRM12). When PCR products were used as probes in genomic Southern and Northern (RNA) analyses, 16 restriction fragments and 25 transcripts, respectively, were detected. Since the combinations of nucleotide sequences represented in the PCR primers correspond to only 4% of the RRM sequences inferred to be possible from known RRM sequences, we estimate the size of the RRM gene family in the order of three hundred genes in flies. In order to gain insight into the possible functions of the genes encoding the RRMs, we analyzed the sequence similarities between the 12 RRMs and 62 RRM sequences of known proteins. This analysis showed that the RRMs of functionally related proteins have similar sequences and are clustered together in the RRM gene tree. On the basis of this observation, the RRMs can be divided into three groups: a heterogeneous nuclear ribonucleoprotein type, a splicing regulator type, and a development-specific factor type. This result suggests that we have isolated good candidates for both housekeeping and developmentally important genes involved in RNA metabolism. Department of Biological Sciences, Stanford University, California 94305. Kim Y J YJ Baker B S BS eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Oligodeoxyribonucleotides 0 RNA, Messenger 0 RNA-Binding Proteins 0 Ribonucleoproteins IM Elav Sxl rbp12 tra-2 Amino Acid Sequence Animal Base Sequence Comparative Study Consensus Sequence Drosophila melanogaster genetics Gene Expression Genes, Structural, Insect Molecular Sequence Data Multigene Family Oligodeoxyribonucleotides chemistry Polymerase Chain Reaction RNA, Messenger genetics RNA-Binding Proteins genetics Ribonucleoproteins chemistry Sequence Alignment Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. FBrf0049482 89276728 2471660 1989 07 24 1989 07 24 2000 12 18

0012-1606 134 1 1989 Jul Molecular cloning of the lethal(1)discs large-1 oncogene of Drosophila. 222-35 We present a genetic, developmental and molecular analysis of lethal(1)discs large-1[l(1)d.lg-1; Stewart et al., 1972], an oncogene of Drosophila. Mutations in this gene cause the imaginal discs to grow by cell proliferation beyond their normal final size, transform into solid tumors, fuse with one another and the brain, and lose their ability to differentiate. The oncogene represents the only known complementation group between two deficiency breakpoints, and 15 recessive lethal alleles are available. Cloning of the DNA between the two deficiency breakpoints defines a region of 45 +/- 2 kb. The l(1)d.lg-1 transcription unit is identified by both qualitative and quantitative effects of several l(1)d.lg-1 mutations on the RNA transcripts and by the presence of a DNA insert in one of the l(1)d.lg-1 alleles. It gives rise to at least five different transcripts ranging in size from 1.9 to 6.0 kb. Three other transcription units are present within this region, two 5' to the l(1)d.lg-1 gene and one at the 3' end. A near full-length cDNA from one of the larger transcripts of l(1)d.lg-1 has homology to genomic DNA spanning over 20 kb. A developmental profile of l(1)d.lg-1 transcription is presented. We discuss how mutations in this gene could disrupt epithelial structure and how this might be related to the excessive cell proliferation and interdisc fusion that is observed. We also compare this gene with another recessive oncogene of Drosophila, lethal(2)giant larvae, that has been cloned and characterized. Developmental Biology Center, University of California, Irvine 92717. Woods D F DF Bryant P J PJ eng HD07029 HD NICHD Journal Article

UNITED STATES Dev Biol 0372762 63231-63-0 RNA 9007-49-2 DNA IM Alleles Animal Cell Communication Cell Differentiation Cell Division Chromosome Mapping Cloning, Molecular DNA genetics Drosophila melanogaster anatomy & histology genetics growth & development Epithelium anatomy & histology Larva growth & development Mutation Nucleic Acid Hybridization Oncogenes RNA analysis genetics Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic Wing anatomy & histology growth & development FBrf0124978 20069333 10601025 2000 01 27 2000 01 27 2002 11 01

0261-4189 18 24 1999 Dec 15 Osa associates with the Brahma chromatin remodeling complex and promotes the activation of some target genes. 7029-40 The yeast SWI/SNF complex and its Drosophila and mammalian homologs are thought to control gene expression by altering chromatin structure, but the mechanism and specificity of this process are not fully understood. The Drosophila osa gene, like yeast SWI1, encodes an AT-rich interaction (ARID) domain protein. We present genetic and biochemical evidence that Osa is a component of the Brahma complex, the Drosophila homolog of SWI/SNF. The ARID domain of Osa binds DNA without sequence specificity in vitro, but it is sufficient to direct transcriptional regulatory domains to specific target genes in vivo. Endogenous Osa appears to promote the activation of some of these genes. We show evidence that some Brahma-containing complexes do not contain Osa and that Osa is not required to localize Brahma to chromatin. These data suggest that Osa modulates the function of the Brahma complex. Skirball Institute for Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, 540/550 First Avenue, New York, NY 10016, USA. Collins R T RT Furukawa T T Tanese N N Treisman J E JE eng GM51314 GM NIGMS GM56131 GM NIGMS Journal Article

ENGLAND EMBO J 8208664 0 Chromatin 0 DNA-Binding Proteins 0 Trans-Activators 0 brahma protein 0 osa protein, Drosophila IM Animal Animals, Genetically Modified Base Pairing Binding Sites Cell Line Cell Nucleus metabolism ultrastructure Chromatin physiology ultrastructure Chromosome Mapping Chromosomes genetics physiology ultrastructure DNA-Binding Proteins genetics metabolism Drosophila melanogaster Gene Expression Regulation Genes, Insect Head Regulatory Sequences, Nucleic Acid Salivary Glands physiology ultrastructure Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism Transcription, Genetic Wing FBrf0084040 96032836 7567454 1995 11 06 1995 11 06 2002 11 01

0305-1048 23 17 1995 Sep 11 Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins. 3441-8 Somatic sex determination in Drosophila depends on the expression of Sex-lethal (Sxl), whose level is determined by the relative number of X chromosomes and sets of autosomes (X:A ratio). The first step in regulation of Sxl expression is transcriptional control from its early promoter and several genes encoding transcription factors of the helix-loop-helix (HLH) family such as daughterless (da), sisterless-b (sis-b), deadpan (dpn) and extramacrochaetae (emc) have been implicated. By the use of transfection assays and in vitro binding experiments, here we show that da/sis-b heterodimers bind several sites on the Sxl early promoter with different affinities and consequently tune the level of active transcription from this promoter. Interestingly, our data indicate that repression by the dpn product of da/sis-b dependent activation results from specific binding of dpn protein to a unique site within the promoter. This contrasts with the mode of emc repression, which inhibits the formation of the da/sis-b heterodimers. These results reveal the molecular mechanisms by which Sxl gene transcription is positively or negatively regulated to control somatic sex determination. Department of Biophysics, Faculty of Science, Kyoto University, Japan. Hoshijima K K Kohyama A A Watakabe I I Inoue K K Sakamoto H H Shimura Y Y eng GENBANK D50435 Journal Article

ENGLAND Nucleic Acids Res 0411011 0 DNA-Binding Proteins 0 Insect Hormones 0 Nuclear Proteins 0 Oligodeoxyribonucleotides 0 RNA, Messenger 0 Repressor Proteins 0 Sxl protein, Drosophila 0 Transcription Factors 0 daughterless protein, Drosophila 0 scute protein, Drosophila 149347-68-2 Dpn protein IM Animal Base Sequence DNA-Binding Proteins genetics metabolism physiology Drosophila melanogaster genetics Gene Expression Regulation Helix-Loop-Helix Motifs Insect Hormones genetics Molecular Sequence Data Nuclear Proteins genetics metabolism Oligodeoxyribonucleotides chemistry Promoter Regions (Genetics) RNA, Messenger genetics Repressor Proteins chemistry Sex Determination (Analysis) Support, Non-U.S. Gov't Transcription Factors metabolism physiology FBrf0080380 95286061 7768443 1995 07 06 1995 07 06 2000 12 18

0016-6731 139 3 1995 Mar Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. 1347-58 The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a growth factor that belongs to the transforming growth factor-beta (TGF-beta) superfamily and that plays a central role in multiple cell-cell signaling events throughout development. Through genetic screens we are seeking to identify other functions that act upstream, downstream or in concert with dpp to mediate its signaling role. We report here the genetic characterization and cloning of Mothers against dpp (Mad), a gene identified in two such screens. Mad loss-of-function mutations interact with dpp alleles to enhance embryonic dorsal-ventral patterning defects, as well as adult appendage defects, suggesting a role for Mad in mediating some aspect of dpp function. In support of this, homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes. We cloned the Mad region and identified the Mad transcription unit through germline transformation rescue. We sequenced a Mad cDNA and identified three Mad point mutations that alter the coding information. The predicted MAD polypeptide lacks known protein motifs, but has strong sequence similarity to three polypeptides predicted from genomic sequence from the nematode Caenorhabditis elegans. Hence, MAD is a member of a novel, highly conserved protein family. Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138, USA. Sekelsky J J JJ Newfeld S J SJ Raftery L A LA Chartoff E H EH Gelbart W M WM eng GENBANK U10327 U10328 U29170 Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Insect Hormones 0 Mad protein 0 dpp protein, Drosophila IM Mad dpp oaf Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Molecular Conserved Sequence genetics DNA-Binding Proteins chemistry genetics Drosophila melanogaster genetics growth & development Enhancer Elements (Genetics) Female Gene Expression Genes, Insect Insect Hormones genetics metabolism Larva cytology genetics Male Molecular Sequence Data Phenotype Point Mutation genetics Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0083217 96028286 7552160 1995 11 03 1995 11 03 2002 11 08

0960-9822 5 6 1995 Jun 1 Morphogenetic signalling. Responses to hedgehog. 580-2 Protein kinase A activity is required for signalling by the extracellular molecule Hedgehog in developing Drosophila imaginal discs, but does the kinase actually respond to the Hedgehog signal? Department of Biological Sciences, Columbia University, New York, New York 10027, USA. Kalderon D D eng Journal Article Review Review, Tutorial

ENGLAND Curr Biol 9107782 0 Homeodomain Proteins 0 Insect Hormones 0 Membrane Proteins 0 Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 dpp protein, Drosophila 0 engrail protein, Drosophila 0 patched protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Cyclic AMP-Dependent Protein Kinases physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Gene Expression Regulation, Developmental Genes, Structural, Insect Homeodomain Proteins genetics physiology Insect Hormones genetics physiology Membrane Proteins genetics physiology Models, Biological Morphogenesis genetics physiology Proteins genetics physiology Proto-Oncogene Proteins genetics physiology Signal Transduction genetics physiology Transcription Factors genetics physiology 15 FBrf0141665 21571938 11715043 2001 11 20 2001 12 07

1471-0056 2 11 2001 Nov Drosophila: genetics meets behaviour. 879-90 Genes are understandably crucial to physiology, morphology and biochemistry, but the idea of genes contributing to individual differences in behaviour once seemed outrageous. Nevertheless, some scientists have aspired to understand the relationship between genes and behaviour, and their research has become increasingly informative and productive over the past several decades. At the forefront of behavioural genetics research is the fruitfly Drosophila melanogaster, which has provided us with important insights into the molecular, cellular and evolutionary bases of behaviour. Department of Zoology, University of Toronto, 3359 Mississauga Road, Mississauga, Ontario, Canada L5L 1C6. msokolow@credit.erin.utoronto.ca Sokolowski M B MB eng Journal Article Review Review, Tutorial

England Nat Rev Genet 100962779 IM Animal Behavior, Animal physiology Circadian Rhythm genetics Drosophila genetics physiology Drosophila melanogaster genetics physiology Learning physiology Memory physiology Motor Activity genetics Phenotype Sex Behavior, Animal physiology Support, Non-U.S. Gov't 121 FBrf0146938 21934942 11937027 2002 04 08 2002 08 27 2003 08 29

0960-9822 12 7 2002 Apr 2 Notch activation of yan expression is antagonized by RTK/pointed signaling in the Drosophila eye. 576-81 Receptor tyrosine kinase (RTK) signaling plays an instructive role in cell fate decisions, whereas Notch signaling is often involved in restricting cellular competence for differentiation. Genetic interactions between these two evolutionarily conserved pathways have been extensively documented. The underlying molecular mechanisms, however, are not well understood. Here, we show that Yan, an Ets transcriptional repressor that blocks cellular potential for specification and differentiation, is a target of Notch signaling during Drosophila eye development. The Suppressor of Hairless (Su[H]) protein of the Notch pathway is required for activating yan expression, and Su(H) binds directly to an eye-specific yan enhancer in vitro. In contrast, yan expression is repressed by Pointed (Pnt), which is a key component of the RTK pathway. Pnt binds specifically to the yan enhancer and competes with Su(H) for DNA binding. This competition illustrates a potential mechanism for RTK and Notch signals to oppose each other. Thus, yan serves as a common target of Notch/Su(H) and RTK/Pointed signaling pathways during cell fate specification. Department of Biochemistry and Molecular Biology, University Park, PA 16802, USA. Rohrbaugh Margaret M Ramos Edward E Nguyen Duc D Price Mitch M Wen Yu Y Lai Zhi Chun ZC eng Journal Article

England Curr Biol 9107782 0 Eye Proteins 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 amino enhancer of split protein 0 anterior open protein, Drosophila 0 notch protein 0 pointed protein 0 suppressor of Hairless protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM Animal Base Sequence Drosophila melanogaster Enhancer Elements (Genetics) Eye Proteins genetics Gene Expression Regulation Membrane Proteins metabolism Molecular Sequence Data Proto-Oncogene Proteins metabolism Receptor Protein-Tyrosine Kinases metabolism Repressor Proteins genetics metabolism Signal Transduction FBrf0084317 96042904 8536967 1996 02 08 1996 02 08 2000 12 18

0016-6731 141 1 1995 Sep Developmental analysis of the ovarian tumor gene during Drosophila oogenesis. 191-202 Severe alleles of the ovarian tumor (otu) and ovo genes result in female sterility in Drosophila melanogaster, producing adult ovaries that completely lack egg chambers. We examined the developmental stage in which the agametic phenotype first becomes apparent. Germ cell development in embryos was studied using a strategy that allowed simultaneous labeling of pole cells with the determination of embryonic genotype. We found that ovo- or otu- XX embryonic germ cells were indistinguishable in number and morphology from those present in wild-type siblings. The effects of the mutations were not consistently manifested in the female germline until pupariation, and there was no evidence that either gene was required for germ cell viability at earlier stages of development. The requirement for otu function in the pupal and adult ovary is supported by temperature-shift experiments using a heat-inducible otu gene construct. We demonstrate that otu activity limited to prepupal stages was not sufficient to support oogenesis, while induction during the pupal and adult periods caused suppression of the otu mutant phenotype. Department of Biological Sciences, University of Iowa, Iowa City 52242, USA. Rodesch C C Geyer P K PK Patton J S JS Bae E E Nagoshi R N RN eng GM-45843 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Heat-Shock Proteins 70 0 Insect Hormones 0 Transcription Factors 0 ovarian tumor protein, Drosophila 0 ovo protein IM Animal Cell Differentiation Cell Survival DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Female Genes, Insect Germ Cells Heat-Shock Proteins 70 genetics Insect Hormones genetics Larva Mutation Oogenesis genetics Promoter Regions (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics Zygote FBrf0102423 98221101 9553038 1998 05 28 1998 05 28 2000 12 18

0890-9369 12 8 1998 Apr 15 Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage. 1086-91 Asymmetric divisions allow a precursor to produce four distinct cells of a Drosophila sensory organ lineage (SOL). Whereas this process requires cell-cell communication via Notch (N) receptor, mitotic recombination that removes the N ligand Delta (Dl) or Serrate (Ser) in the SOL had mild or no effect. Removal of both Dl and Ser, however, led to cell fate transformations similar to the N phenotype. Cell fate transformation occurred even when a single SOL cell lost both Dl and Ser. Thus, Dl and Ser are redundant in mediating signaling between daughter cells to specify their distinct cell fates. Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco, California 94143, USA. Zeng C C Younger-Shepherd S S Jan L Y LY Jan Y N YN eng 416-5 PHS Journal Article

UNITED STATES Genes Dev 8711660 0 Ligands 0 Membrane Proteins 0 Receptors, Cell Surface 0 delta protein 0 notch protein 134324-36-0 Serrate protein IM Animal Cell Differentiation Cell Division Drosophila melanogaster Ligands Membrane Proteins metabolism physiology Phenotype Receptors, Cell Surface metabolism Sense Organs cytology metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Wing FBrf0076971 95021209 7935398 1994 10 21 1994 10 21 2000 12 18

0270-7306 14 10 1994 Oct Multiple products from the shavenbaby-ovo gene region of Drosophila melanogaster: relationship to genetic complexity. 6809-18 The Drosophila melanogaster shavenbaby (svb)-ovo gene region is a complex locus, containing two distinct but comutable genetic functions. ovo is required for survival and differentiation of female germ line cells and plays a role in germ line sex determination. In contrast, svb is required in both male and female embryos for the production of epidermal locomotor and sensory structures. Sequences required for the two genetic functions are partially overlapping. ovo corresponds to a previously described germ line-dependent 5.0-kb poly(A)+ mRNA that first appears in the germarium and accumulates in nurse cells during oogenesis. The 5.0-kb mRNA is stored in the egg, but it is rapidly lost in the embryos except for its continued presence in the germ line precursor pole cells. The ovo mRNA predicts a 1,028-amino-acid 110.6-kDa protein homologous with transcription factors. We have identified an embryonic mRNA, 7.1 kb in length, that contains exons partially overlapping those of the 5.0-kb poly(A)+ mRNA. The spatial distribution of this newly discovered transcript during midembryogenesis suggests that it corresponds to the svb function. The arrangement of exons common to the 5.0- and 7.1-kb mRNAs suggests that the Ovo and Svb proteins share DNA-binding specificity conferred by four Cys2-His2 zinc finger motifs but differ functionally in their capacity to interact with other components of the transcription machinery. Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637. Garfinkel M D MD Wang J J Liang Y Y Mahowald A P AP eng GENBANK U10670 U10671 U11383 CA14599-20 CA NCI RO1 HD17608 HD NICHD Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA, Complementary 0 DNA-Binding Proteins 0 RNA, Messenger 0 Transcription Factors 0 ovo protein 24937-83-5 Poly A IM ovo svb Amino Acid Sequence Animal Base Sequence Blotting, Northern Cloning, Molecular DNA, Complementary genetics DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Female Genes, Insect genetics In Situ Hybridization Male Molecular Sequence Data Ovary metabolism Poly A biosynthesis RNA Processing, Post-Transcriptional RNA Splicing RNA, Messenger genetics Support, U.S. Gov't, P.H.S. Tissue Distribution Transcription Factors genetics Transcription, Genetic FBrf0160398 22640874 12756182 2003 05 20 2003 09 10

0950-1991 130 13 2003 Jul Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. 3007-14 Planar polarity decisions in the wing of Drosophila involve the assembly of asymmetric protein complexes containing the conserved receptor Frizzled. In this study, we analyse the role of the Van Gogh/strabismus gene in the formation of these complexes and cell polarisation. We find that the Strabismus protein becomes asymmetrically localised to the proximal edge of cells. In the absence of strabismus activity, the planar polarity proteins Dishevelled and Prickle are mislocalised in the cell. We show that Strabismus binds directly to Dishevelled and Prickle and is able to recruit them to membranes. Furthermore, we demonstrate that the putative PDZ-binding motif at the C terminus of Strabismus is not required for its function. We propose a two-step model for assembly of Frizzledcontaining asymmetric protein complexes at cell boundaries. First, Strabismus acts together with Frizzled and the atypical cadherin Flamingo to mediate apicolateral recruitment of planar polarity proteins including Dishevelled and Prickle. In the second phase, Dishevelled and Prickle are required for these proteins to become asymmetrically distributed on the proximodistal axis. Centre for Developmental Genetics, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK. Bastock Rebecca R Strutt Helen H Strutt David D eng Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Dsh protein 0 Macromolecular Systems 0 Membrane Proteins 0 Phosphoproteins 0 Receptors, Cell Surface 0 Recombinant Fusion Proteins 0 frizzled protein, Drosophila 0 prickle protein, Drosophila 0 strabismus protein IM Animal Body Patterning physiology Cell Line Cell Polarity physiology DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster anatomy & histology embryology genetics growth & development Embryonic Structures cytology physiology Macromolecular Systems Membrane Proteins genetics metabolism Models, Biological Phosphoproteins genetics metabolism Protein Binding Receptors, Cell Surface metabolism Recombinant Fusion Proteins metabolism Support, Non-U.S. Gov't Transgenes Wing anatomy & histology growth & development FBrf0132215 21114504 11178240 2001 02 22 2001 08 30 2003 01 03

1465-6914 1 3 2000 A comparison of programmed cell death between species. REVIEWS0003 Key components of the programmed cell death pathway are conserved between Caenorhabditis elegans, Drosophila melanogaster and humans. The search for additional homologs has been facilitated by the availability of the entire genomic sequence for each of these organisms. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Tittel J N JN Steller H H eng Journal Article Review Review, Tutorial 2000 09 13

England Genome Biol 100960660 IM Animal Apoptosis genetics physiology Caenorhabditis elegans cytology genetics physiology Comparative Study Conserved Sequence Drosophila melanogaster cytology genetics physiology Genomics Human Signal Transduction Species Specificity 53 FBrf0111849 20021614 10555143 1999 11 23 1999 11 23 2003 06 16

0092-8674 99 3 1999 Oct 29 Novel functions of nanos in downregulating mitosis and transcription during the development of the Drosophila germline. 271-81 It has previously been shown that germ cells in embryos derived from nos mutant mothers do not migrate to the primitive gonad and prematurely express several germline-specific markers. In the studies reported here, we have traced these defects back to the syncytial blastoderm stage. We show that pole cells in nos embryos fail to establish/maintain transcriptional quiescence; the sex determination gene Sex-lethal (Sxl) and the segmentation genes fushi tarazu and even-skipped are ectopically activated in nos- germ cells. We show that nos- germ cells are unable to attenuate the cell cycle and instead continue dividing. Unexpectedly, removal of the Sxl gene in the zygote mitigates both the migration and mitotic defects of nos- germ cells. Supporting the conclusion that Sxl is an important target for nos repression, ectopic, premature expression of Sxl protein in germ cells disrupts migration and stimulates mitotic activity. Department of Molecular Biology, Princeton University, New Jersey 08544, USA. gdeshpande@molbio.princeton.edu Deshpande G G Calhoun G G Yanowitz J L JL Schedl P D PD eng Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 ESPD protein, E coli 0 Homeodomain Proteins 0 Insect Proteins 0 Repressor Proteins 0 Transcription Factors 0 fushi tarazu protein 108911-13-3 even-skipped protein, Drosophila 135471-20-4 T-cell acute lymphocytic leukemia 1 protein 142661-95-8 nanos protein, Drosophila IM Animal Blastoderm cytology physiology DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian cytology physiology Female Gastrula cytology physiology Gene Expression Regulation, Developmental Homeodomain Proteins genetics Insect Proteins genetics metabolism Male Mitosis genetics Morphogenesis Repressor Proteins genetics Support, U.S. Gov't, P.H.S. Transcription Factors genetics Transcription, Genetic FBrf0151938 22291604 12403714 2002 10 29 2003 01 21 2003 06 16

0950-1991 129 23 2002 Dec The Drosophila cytokine receptor Domeless controls border cell migration and epithelial polarization during oogenesis. 5437-47 In mammals, the JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) signaling pathway is activated in response to cytokines and growth factors to control blood cell development, proliferation and cell determination. In Drosophila, a conserved JAK/STAT signaling pathway controls segmentation in embryos, as well as blood cell development and other processes in larvae and adults. During embryogenesis, transduction of the Unpaired [Upd; also known as Outstretched (Os)] ligand through the JAK/STAT pathway requires Domeless, a putative membrane protein with distant homology to vertebrate type I cytokine receptors. We have isolated domeless (dome) in a screen to identify genes essential in epithelial morphogenesis during oogenesis. The level of dome activity is critical for proper border cell migration and is controlled in part through a negative feedback loop. In addition to its essential role in border cells, we show that dome is required in the germarium for the polarization of follicle cells during encapsulation of germline cells. In this process, dome controls the expression of the apical determinant Crumbs. In contrast to the ligand Upd, whose expression is limited to a pair of polar cells at both ends of the egg chamber, dome is expressed in all germline and follicle cells. However, the Dome protein is specifically localized at apicolateral membranes and undergoes ligand-dependent internalization in the follicle cells. dome mutations interact genetically with JAK/STAT pathway genes in border cell migration and abolish the nuclear translocation of Stat92E in vivo. We also show that dome functions downstream of upd and that both the extracellular and intracellular domains of Dome are required for JAK/STAT signaling. Altogether, our data indicate that Dome is an essential receptor molecule for Upd and JAK/STAT signaling during oogenesis. Institute of Signaling, Developmental Biology and Cancer, UMR 6543 - CNRS, Parc Valrose, 06108 NICE cedex 2, France. Ghiglione Christian C Devergne Olivier O Georgenthum Emmanuelle E Carballès Fabrice F Médioni Caroline C Cerezo Delphine D Noselli Stéphane S eng Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Glycoproteins 0 Insect Proteins 0 Receptors, Interleukin 0 Recombinant Fusion Proteins 0 Trans-Activators 0 domeless protein, Drosophila 0 gamma-activated factor, 91-kD 0 outstretched protein, Drosophila EC 2.7.1.- Janus kinase 1 EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal Animals, Genetically Modified Cell Movement physiology Cell Polarity DNA-Binding Proteins metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics physiology Epithelial Cells metabolism Female Gene Expression Regulation, Developmental Genes, Reporter Genes, Structural, Insect Glycoproteins metabolism Insect Proteins metabolism Morphogenesis Oogenesis physiology Ovarian Follicle cytology metabolism Protein-Tyrosine Kinase metabolism Receptors, Interleukin genetics metabolism Recombinant Fusion Proteins genetics metabolism Signal Transduction physiology Support, Non-U.S. Gov't Trans-Activators metabolism FBrf0092642 97225212 9071585 1997 07 24 1997 07 24 2000 12 18

0016-6731 145 2 1997 Feb Molecular evolution at the decapentaplegic locus in Drosophila. 297-309 Using an elaborate set of cis-regulatory sequences, the decapentaplegic (dpp) gene displays a dynamic pattern of gene expression during development. The C-terminal portion of the DPP protein is processed to generate a secreted signaling molecule belonging to the transforming growth factor-beta (TGF-beta) family. This signal, the DPP ligand, is able to influence the developmental fates of responsive cells in a concentration-dependent fashion. Here we examine the sequence level organization of a significant portion of the dpp locus in Drosophila melanogaster and use interspecific comparisons with D. simulans, D. pseudoobscura and D.virilis to explore the molecular evolution of the gene. Our interspecific analysis identified significant selective constraint on both the nucleotide and amino acid sequences. As expected, interspecific comparison of protein coding sequences shows that the C-terminal ligand region is highly conserved. However, the central portion of the protein is also conserved, while the N-terminal third is quite variable. Comparison of noncoding regions reveals significant stretches of nucleotide identity in the 3' untranslated portion of exon 3 and in the intron between exons 2 and 3. An examination of cDNA sequences representing five classes of dpp transcripts indicates that these transcripts encode the same polypeptide. Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138, USA. Newfeld S J SJ Padgett R W RW Findley S D SD Richter B G BG Sanicola M M de Cuevas M M Gelbart W M WM eng GENBANK U63850 U63851 U63852 U63853 U63854 U63855 U63856 U63857 Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping DNA Drosophila genetics Drosophila melanogaster genetics Evolution, Molecular Insect Proteins genetics Introns Molecular Sequence Data Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. Transforming Growth Factor beta genetics Translation, Genetic FBrf0051939 91060070 2123161 1991 01 09 1991 01 09 2000 12 18

0016-6731 126 2 1990 Oct Genetic analysis of transvection effects involving cis-regulatory elements of the Drosophila Ultrabithorax gene. 365-73 The Ultrabithorax (Ubx) gene of Drosophila melanogaster contains two functionally distinguishable regions: the protein-coding Ubx transcription unit and, upstream of it, the transcribed but nonprotein-coding bxd region. Numerous recessive, partial loss-of-function mutations which appear to be regulatory mutations map within the bxd region and within the introns of the Ubx transcription unit. In addition, mutations within the Ubx unit exons are known and most of these behave as null alleles. Ubx1 is one such allele. We have confirmed that, although the Ubx1 allele does not produce detectable Ubx proteins (UBX), it does retain other genetic functions detectable by their effects on the expression of a paired, homologous Ubx allele, i.e., by transvection. We have extended previous analyses made by E. B. Lewis by mapping the critical elements of the Ubx gene which participate in transvection effects. Our results show that the Ubx1 allele retains wild-type functions whose effectiveness can be reduced (1) by additional cis mutations in the bxd region or in introns of the Ubx transcription unit, as well as (2) by rearrangements disturbing pairing between homologous Ubx genes. Our results suggest that those remnant functions in Ubx1 are able to modulate the activity of the allele located in the homologous chromosome. We discuss the normal cis regulatory role of these functions involved in trans interactions between homologous Ubx genes, as well as the implications of our results for the current models on transvection. Centro de Biología Molecular, C.S.I.C.-Universidad Autónoma de Madrid, Spain. Micol J L JL Castelli-Gair J E JE García-Bellido A A eng Journal Article

UNITED STATES Genetics 0374636 IM Ubx Alleles Animal Drosophila melanogaster genetics Gene Expression Regulation Genes Genes, Recessive Genotype Heterozygote Mutation Phenotype Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't Transfection FBrf0151325 22123407 12130542 2002 07 19 2002 08 23 2003 06 16

0890-9369 16 14 2002 Jul 15 The transcriptional repressor Brinker antagonizes Wingless signaling. 1828-38 In the embryonic midgut of Drosophila, Wingless (Wg) signaling elicits threshold-specific transcriptional response, that is, low-signaling levels activate target genes, whereas high-signaling levels repress them. Wg-mediated repression of the HOX gene Ultrabithorax (Ubx) is conferred by a response sequence within the Ubx B midgut enhancer, called WRS-R. It further depends on the Teashirt (Tsh) repressor, which acts through the WRS-R without binding to it. Here, we show that Wg-mediated repression of Ubx B depends on Brinker, which binds to the WRS-R. Furthermore, Brinker blocks transcriptional activation by ubiquitous Wg signaling. Brinker binds to Tsh in vitro, recruits Tsh to the WRS-R, and we find mutual physical interactions between Brinker, Tsh, and the corepressor dCtBP. This suggests that the three proteins may form a ternary repressor complex at the WRS-R to quench the activity of the nearby-bound dTCF/Armadillo transcription complex. Finally, brinker and tsh produce similar mutant phenotypes in the ventral epidermis, and double mutants mimic overactive Wg signaling in this tissue. This suggests that Brinker may have a widespread function in antagonizing Wg signaling. Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 2QH, UK. Saller Elisabeth E Kelley Ann A Bienz Mariann M eng Journal Article

United States Genes Dev 8711660 0 C-terminal binding protein 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Insect Proteins 0 Phosphoproteins 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 Transcription Factors 0 brinker protein, Drosophila 117758-26-6 wingless protein, Drosophila 135315-85-4 tsh protein IM Animal DNA-Binding Proteins genetics metabolism Digestive System metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics metabolism Epidermis embryology metabolism Insect Proteins genetics metabolism Phosphoproteins genetics metabolism Proto-Oncogene Proteins genetics metabolism Repressor Proteins genetics metabolism Signal Transduction Support, Non-U.S. Gov't Transcription Factors genetics metabolism Transcription, Genetic FBrf0081941 95250186 7732572 1995 05 30 1995 05 30 2002 11 01

0168-9525 11 3 1995 Mar Nuclear factors in sevenless signalling. 106-11 Recent studies in both vertebrates and invertebrates support an 'hourglass' model for signal transduction from receptor tyrosine kinases: Ras channels signals from diverse receptor tyrosine kinases into a common cytoplasmic kinase cascade, the targets of which are an even more diverse collection of nuclear proteins. What are these nuclear factors, and how do they interact to direct specific cellular responses to a generic signal? The past year has brought considerable progress in our quest to answer these questions in one model genetic system, the Drosophila eye. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA. Dickson B B eng Journal Article Review Review, Tutorial

ENGLAND Trends Genet 8507085 0 DNA-Binding Proteins 0 Eye Proteins 0 Membrane Glycoproteins 0 Nuclear Proteins 0 Proto-Oncogene Proteins 0 Transcription Factor AP-1 0 anterior open protein, Drosophila 0 phyllopod protein 0 pointed protein 0 seven in absentia protein 0 sevenless protein IM D-jun Psc RAG1 Ras1 Su(z)2 bmi-1 boss fos fra jun phyl pnt raf ras sev sina yan Animal Cell Differentiation genetics DNA-Binding Proteins physiology Drosophila melanogaster genetics Eye Proteins genetics physiology Gene Expression Regulation, Developmental Genes, Structural, Insect Membrane Glycoproteins genetics physiology Models, Biological Nuclear Proteins genetics physiology Phosphorylation Photoreceptors, Invertebrate growth & development Protein Processing, Post-Translational Proto-Oncogene Proteins physiology Signal Transduction physiology Support, Non-U.S. Gov't Transcription Factor AP-1 physiology 50 FBrf0105862 99069220 9851979 1999 01 19 1999 01 19 2003 08 29

0890-9369 12 23 1998 Dec 1 Ligand-induced cleavage and regulation of nuclear entry of Notch in Drosophila melanogaster embryos. 3728-40 Notch, a transmembrane protein found in a wide range of organisms, is a component of a pathway that mediates cell-fate decisions that involve intercellular communication. In this paper, we show that in Drosophila melanogaster, Notch (N) is processed in a ligand-dependent fashion to generate phosphorylated, soluble intracellular derivatives. Suppressor of Hairless [Su(H)] is predominantly associated with soluble intracellular N. It has been demonstrated by others that N has access to the nucleus, and we show that when tethered directly to DNA, the cytoplasmic domain of N can activate transcription. Conversely, a viral activator fused to Su(H) can substitute for at least some N functions during embryogenesis. We suggest that one function of soluble forms of N is to bind to Su(H), and in the nucleus, to act directly as a transcriptional transactivator of the latter protein. Although N has functional nuclear localization signals, the N/Su(H) complex accumulates in the cytoplasm and on membranes suggesting that its nuclear entry is regulated. Localization studies in cultured cells and embryos suggest that Su(H) plays a role in this regulation, with the relative levels of Delta, N and Su(H) determining whether a N/Su(H) complex enters the nucleus. Laboratory of Genetics, The Rockefeller University, New York, New York 10021-6399 USA. Kidd S S Lieber T T Young M W MW eng GM25103 GM NIGMS Journal Article

UNITED STATES Genes Dev 8711660 0 DNA-Binding Proteins 0 Ligands 0 Membrane Proteins 0 Nuclear Proteins 0 Phosphoproteins 0 Repressor Proteins 0 Trans-Activators 0 dorsal protein, Drosophila 0 notch protein 0 suppressor of Hairless protein, Drosophila IM Animal Biological Transport Cell Compartmentation Cell Nucleus metabolism Cytoplasm metabolism DNA-Binding Proteins metabolism Drosophila melanogaster embryology Ligands Membrane Proteins metabolism Nuclear Proteins metabolism Phosphoproteins metabolism Protein Binding Protein Processing, Post-Translational Repressor Proteins metabolism Support, U.S. Gov't, P.H.S. Trans-Activators metabolism FBrf0160886 22767828 12885551 2003 07 29 2003 09 24

0012-1606 260 1 2003 Aug 1 Signaling systems, guided cell migration, and organogenesis: insights from genetic studies in Drosophila. 1-8 During development, cells change their position extensively. Although the basic cellular mechanisms involved in cell locomotion have been studied mostly in cultured cells, genetic and molecular approaches using model organisms are starting to shed light on the complex events influencing cell migration during development. Recent technical advances in following and analyzing migrating cells inside the living embryo offer the possibility of understanding how different signaling systems regulate the fundamental cellular processes underlying guided cell migration in vivo. In Drosophila melanogaster, studies of migrating cells have concentrated mainly on hemocytes, germ cells, border cells, and tracheal cells. Interestingly, most of these cells were recently shown to make different cellular extensions and to use receptor tyrosine kinases to sense the chemoattractive signal. This review describes our current understanding of how different signaling networks control guided migration in these four systems and discusses the impact of novel imaging techniques on the study of guided cell migration during development. Biozentrum der Universität Basel, Department of Cell Biology, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Ribeiro Carlos C Petit Valérie V Affolter Markus M eng Journal Article Review Review, Tutorial

United States Dev Biol 0372762 EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM Animal Cell Movement genetics Drosophila embryology genetics Embryo, Nonmammalian cytology Female Germ Cells cytology metabolism Hemocytes cytology metabolism Models, Biological Organogenesis Receptor Protein-Tyrosine Kinases metabolism Signal Transduction Support, Non-U.S. Gov't Trachea cytology embryology metabolism 65 FBrf0055059 92022537 1925551 1991 11 07 1991 11 07 2000 12 18

0036-8075 254 5028 1991 Oct 4 Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. 118-22 A gradient of the maternal morphogen dorsal establishes asymmetric patterns of gene expression along the dorsal-ventral axis of early embryos and activates the regulatory genes twist and snail, which are responsible for the differentiation of the ventral mesoderm. Expression of snail is restricted to the presumptive mesoderm, and the sharp lateral limits of this expression help to define the mesoderm-neuroectoderm boundary by repressing the expression of regulatory genes that are responsible for the differentiation of the neuroectoderm. The snail gene encodes a zinc finger protein, and neuroectodermal genes that are normally restricted to ventral-lateral regions of early embryos are expressed throughout ventral regions of snail- mutants. The formation of the sharp snail border involves dosage-sensitive interactions between dorsal and twist, which encode regulatory proteins that are related to the mammalian transcription factors NF-kB and MyoD, respectively. Biology Department, University of California, San Diego, La Jolla 92093. Kosman D D Ip Y T YT Levine M M Arora K K eng GM 46638 GM NIGMS Journal Article

UNITED STATES Science 0404511 0 DNA Probes 0 DNA-Binding Proteins 0 Nuclear Proteins 0 twist protein IM T3 dl rho sna twi Animal DNA Probes DNA-Binding Proteins metabolism Drosophila melanogaster embryology Ectoderm cytology physiology Embryonic Induction Gene Expression Regulation Mesoderm cytology physiology Morphogenesis Nervous System embryology Nuclear Proteins metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zinc Fingers FBrf0076809 94364975 8083185 1994 10 11 1994 10 11 2000 12 18

0021-9258 269 37 1994 Sep 16 A "slow" homotetrameric kinesin-related motor protein purified from Drosophila embryos. 22913-6 Pan-kinesin peptide antibodies (Cole, D. G., Cande, W. Z., Baskin, R. J., Skoufias, D. A., Hogan, C. J., and Scholey, J. M. (1992) J. Cell Sci. 101, 291-301; Sawin, K. E., Mitchinson, T. J., and Wordeman, L. G. (1992) J. Cell Sci. 101, 303-313) were used to identify and isolate kinesin-related proteins (KRPs) from Drosophila melanogaster embryonic cytosol. These KRPs cosedimented with microtubules (MTs) polymerized from cytosol treated with AMP-PNP (adenyl-5'-yl imidodiphosphate), and one of them, KRP130, was further purified from ATP eluates of the embryonic MTs. Purified KRP130 behaves as a homotetrameric complex composed of four 130-kDa polypeptide subunits which displays a "slow" plus-end directed motor activity capable of moving single MTs at 0.04 +/- 0.01 microns/s. The 130-kDa subunit of KRP130 was tested for reactivity with monoclonal and polyclonal antibodies that are specific for various members of the kinesin superfamily. Results indicate that the KRP130 subunit is related to Xenopus Eg5 (Sawin, K. E., Le Guellec, K. L., Philippe, M., Mitchinson, T. J. (1992) Nature 359, 540-543), a member of the BimC subfamily of kinesins. Therefore, KRP130 appears to be the first Drosophila KRP, and the first member of the BimC subfamily in any organism, to be purified from native tissue as a multimeric motor complex. Section of Molecular and Cellular Biology, University of California, Davis 95616. Cole D G DG Saxton W M WM Sheehan K B KB Scholey J M JM eng GM46295 GM NIGMS GM46376 GM NIGMS IF32AR08173 AR NIAMS Journal Article

UNITED STATES J Biol Chem 2985121R 0 Microtubule-Associated Proteins EC 3.6.1.- Kinesin IM Animal Centrifugation, Density Gradient Chromatography, Gel Drosophila melanogaster chemistry embryology Electrophoresis, Polyacrylamide Gel Kinesin chemistry Larva chemistry Microtubule-Associated Proteins chemistry isolation & purification Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0055564 93046645 1423606 1992 12 08 1992 12 08 2000 12 18

0092-8674 71 3 1992 Oct 30 Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. 451-61 Zygotic expression of the Drosophila TGF beta family member decapentaplegic (dpp) is required for the development of the dorsal embryonic structures. By injecting dpp transcripts into young embryos, we find that 2- to 4-fold increases in the concentration of injected RNA elicit progressively more dorsal cell fates: only low levels of dpp permit development of ventral ectoderm, intermediate dpp levels drive dorsal epidermal development, and high dpp levels drive cells to differentiate as the most dorsal pattern element, the amnioserosa. Localized dpp RNA injections into embryos that lack all known maternal and zygotic dorsal-ventral polarity indicate that dpp can both define embryonic polarity and organize detailed patterning within the ectoderm. We infer that dpp acts as an extracellular morphogen and that the graded activity of dpp specifies the pattern of ectodermal cell fates in the Drosophila embryo. Department of Molecular and Cell Biology, University of California, Berkeley 94720. Ferguson E L EL Anderson K V KV eng GM 35437 GM NIGMS HD07299 HD NICHD Journal Article

UNITED STATES Cell 0413066 0 Insect Hormones 0 RNA, Messenger 0 Transforming Growth Factor beta 0 dpp protein, Drosophila IM dpp Animal Cell Differentiation Drosophila melanogaster embryology Ectoderm Gastrula Insect Hormones physiology Morphogenesis RNA, Messenger administration & dosage Support, U.S. Gov't, P.H.S. Transforming Growth Factor beta physiology FBrf0091294 97164689 9012496 1997 02 24 1997 02 24 2003 06 16

0950-1991 122 12 1996 Dec Pointed, an ETS domain transcription factor, negatively regulates the EGF receptor pathway in Drosophila oogenesis. 3745-54 Spatially regulated activation of the Drosophila epidermal growth factor (EGF) receptor by its ligand, Gurken, is required for establishment of the dorsal/ventral axis of the oocyte and embryo. During mid-oogenesis, Gurken is concentrated at the dorsal-anterior of the oocyte and is thought to activate the EGF receptor pathway in adjacent follicle cells. In response to this signal, dorsal follicle cell fate is determined. These cells further differentiate into either appendage-producing or midline cells, resulting in patterning in the dorsal follicle cell layer. We show here that Pointed, an ETS transcription factor, is required in dorsal follicle cells for this patterning. Loss of pointed results in the loss of midline cells and an excess of appendage-forming cells, a phenotype associated with overactivation of the EGF receptor pathway in the dorsal region. Overexpression of pointed leads to a phenotype similar to that generated by loss of the EGF receptor pathway. This suggests that Pointed normally down-regulates EGF receptor signaling in the midline to generate patterning in the dorsal region. Interestingly, pointed expression is induced by the EGF receptor pathway. These data indicate a novel antagonistic function for Pointed in oogenesis; in response to activation of the EGF receptor, pointed is expressed and negatively regulates the EGF receptor pathway, possibly by integrating information from a second pathway. Department of Biochemistry, University of Washington, Seattle 98195, USA. Morimoto A M AM Jordan K C KC Tietze K K Britton J S JS O'Neill E M EM Ruohola-Baker H H eng R01 HD 32464 HD NICHD T32 GM07270 GM NIGMS Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 Proto-Oncogene Proteins 0 Transcription Factors 0 gurken protein, Drosophila 0 pointed protein 76057-06-2 Transforming Growth Factors EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Body Patterning physiology Drosophila melanogaster cytology embryology growth & development Female Insect Hormones metabolism Models, Biological Morphogenesis Oogenesis physiology Proto-Oncogene Proteins metabolism Receptor, Epidermal Growth Factor metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tissue Distribution Transcription Factors metabolism Transforming Growth Factors metabolism FBrf0091210 97134670 8980230 1997 02 03 1997 02 03 2000 12 18

0092-8674 87 7 1996 Dec 27 A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. 1237-47 In a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro. Overexpressing dap during eye development interferes with cell cycle progression and interacts genetically with the retinoblastoma homolog (Rbf) and cyclin E. dap expression in embryos parallels the exit of cells from the cell cycle. dap mutant embryos delay the normal cell cycle exit during development; many cells complete an additional cycle and subsequently become quiescent. Thus, dap functions during embryogenesis to achieve a precisely timed exit from the cell cycle. Massachusetts General Hospital Cancer Center, Charlestown 02129, USA. de Nooij J C JC Letendre M A MA Hariharan I K IK eng GENBANK U77937 Journal Article

UNITED STATES Cell 0413066 0 Cyclins 0 Decapo protein 0 Enzyme Inhibitors 0 Growth Inhibitors 0 Insect Proteins 0 Nuclear Proteins 0 RNA, Messenger EC 2.7.1.- CDK2 protein EC 2.7.1.- histone H1 kinase EC 2.7.1.37 Cyclin-Dependent Kinases EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Amino Acid Sequence Animal Cell Cycle Cloning, Molecular Cyclin-Dependent Kinases antagonists & inhibitors Cyclins antagonists & inhibitors Drosophila melanogaster embryology enzymology Enzyme Inhibitors Epidermis cytology Eye embryology Gene Expression Regulation, Developmental Genes, Lethal Genes, Structural, Insect Growth Inhibitors Insect Proteins physiology Molecular Sequence Data Mutagenesis, Insertional Nuclear Proteins physiology Protein Kinases antagonists & inhibitors Protein-Serine-Threonine Kinases antagonists & inhibitors RNA, Messenger genetics Sequence Alignment Support, Non-U.S. Gov't FBrf0050618 89295595 2500601 1989 08 08 1989 08 08 2001 11 02

0028-0836 340 6229 1989 Jul 13 Effect on eye development of dominant mutations in Drosophila homologue of the EGF receptor. 150-3 The compound eye of the adult fruitfly, Drosophila melanogaster, comprises about 800 identical ommatidia, or unit eyes, each containing 20 distinct cells. We have used histological and immunocytochemical methods to study the development of the compound eye in Ellipse (Elp) mutants. In Elp/Elp, most ommatidia do not initiate differentiation. We present genetic evidence that Elp alleles are mutations of the Drosophila homologue of the epidermal growth factor (EGF) receptor, and suggest that activity of the EGF receptor may determine the spacing pattern of ommatidia in the eye. Howard Hughes Medical Institute, University of California, Berkeley 94720. Baker N E NE Rubin G M GM eng Journal Article

ENGLAND Nature 0410462 EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Cell Differentiation Chromosome Deletion Drosophila melanogaster genetics growth & development Embryo, Nonmammalian Eye cytology growth & development Female Genes, Dominant Male Mutation Ocular Physiology Phenotype Receptor, Epidermal Growth Factor genetics physiology Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't FBrf0051973 91065504 2123463 1991 01 14 1991 01 14 2000 12 18

0016-6731 126 3 1990 Nov The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VII. Characterization of the region around the snail and cactus loci. 679-94 The genetic interval 35C to 36A on chromosome arm 2L of Drosophila melanogaster has been saturated for mutations with visible or lethal phenotypes. 38 loci have been characterized, including several maternal-effect lethals (vasa, Bic-C, chiffon, cactus and cornichon) and several early embryonic lethals, including snail and fizzy. About 130 deletions have been used to order these loci. Complex interactions between mutant alleles have been uncovered in the immediate genetic environs of the snail gene, as has further evidence for an interaction between this region and that including the nearby genes no-ocelli and elbow. Department of Genetics, University of Cambridge, England. Ashburner M M Thompson P P Roote J J Lasko P F PF Grau Y Y el Messal M M Roth S S Simpson P P eng Journal Article

UNITED STATES Genetics 0374636 EC 1.1.1.1 Alcohol Dehydrogenase IM Alcohol Dehydrogenase genetics metabolism Alleles Animal Chromosome Deletion Drosophila melanogaster genetics Genes, Structural Genotype Heterozygote Homozygote Linkage (Genetics) Mutation Phenotype Recombination, Genetic Support, Non-U.S. Gov't FBrf0146956 21559212 11702944 2001 11 12 2001 12 07

1534-5807 1 3 2001 Sep Rac 'n Rho: the music that shapes a developing embryo. 321-31 The small GTPases of the Rho subfamily constitute a group of evolutionarily conserved proteins that mediate signaling pathways that regulate a variety of cellular processes, many of which are associated with dynamic cytoskeletal reorganization. These processes determine the shape, adhesive properties, and movement of cells, and the Rho GTPases have therefore been implicated in the complex morphogenesis of tissues in developing multicellular organisms. The Drosophila genetic system has proved particularly useful in establishing the in vivo functions of several of the Rho GTPases and their associated signaling pathway components during development. Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA. settleman@helix.mgh.harvard.edu Settleman J J eng Journal Article Review Review, Tutorial

United States Dev Cell 101120028 86-01-1 Guanosine Triphosphate EC 3.6.1.- rac GTP-Binding Proteins EC 3.6.1.- rho GTP-Binding Proteins IM Animal Cell Division Cell Polarity Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian growth & development Guanosine Triphosphate metabolism Models, Biological Neurons metabolism Signal Transduction physiology rac GTP-Binding Proteins genetics metabolism rho GTP-Binding Proteins genetics metabolism 66 FBrf0072686 94374680 7916308 1994 10 20 1994 10 20 2000 12 18

0016-6731 137 3 1994 Jul Genetic analysis of the brahma gene of Drosophila melanogaster and polytene chromosome subdivisions 72AB. 803-13 The brahma gene is required for activation of the homeotic genes of the Antennapedia and bithorax complexes in Drosophila. We have isolated and characterized 21 mutations in brahma. We show that both maternal and zygotic functions of brahma are required during embryogenesis. In addition, the severe abnormalities caused by loss of maternal brahma expression show that the homeotic genes are not the only targets for brahma activation. The complex pattern of interallelic complementation for the 21 brahma alleles suggests that brahama may act as a multimer. In addition to mutations in brahma, we have isolated mutations in four other essential genes within polytene chromosome subdivisions 72AB. Based on a compilation of similar studies that include about 24% of the genome, we estimate that about 3600 genes in Drosophila can mutate to cause recessive lethality, with fewer than 900 additional genes essential only for gametogenesis. We have identified three times more transcripts than lethal complementation groups in 72AB. One transcript in 72AB is the product of the essential arf-like gene and encodes a member of the ARF subfamily of small GTP-binding proteins. Two other transcripts are probably the products of a single gene whose protein products are similar to the catalytic subunits of cAMP-dependent protein kinases. Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Brizuela B J BJ Elfring L L Ballard J J Tamkun J W JW Kennison J A JA eng Journal Article

UNITED STATES Genetics 0374636 0 Arl3 protein 0 RNA, Messenger 0 Trans-Activators 0 brahma protein EC 3.6.1.- GTP-Binding Proteins IM arl brm pc Alleles Animal Blotting, Northern Chromosome Mapping Crosses, Genetic Drosophila melanogaster embryology genetics Embryo, Nonmammalian growth & development Epistasis, Genetic Female Fertility genetics GTP-Binding Proteins genetics Gene Expression Regulation Genes, Homeobox physiology Genes, Insect Genes, Lethal Genetic Complementation Test Genomic Library Male Mothers Multigene Family Mutation RNA, Messenger analysis Support, Non-U.S. Gov't Trans-Activators genetics physiology FBrf0132410 20576877 11134347 2001 02 02 2001 02 02 2002 11 01

0270-7306 21 2 2001 Jan Prodos is a conserved transcriptional regulator that interacts with dTAF(II)16 in Drosophila melanogaster. 614-23 The transcription factor TFIID is a multiprotein complex that includes the TATA box binding protein (TBP) and a number of associated factors, TAF(II). Prodos (PDS) is a conserved protein that exhibits a histone fold domain (HFD). In yeast two-hybrid tests using PDS as bait, we cloned the Drosophila TAF(II), dTAF(II)16, as a specific PDS target. dTAF(II)16 is closely related to human TAF(II)30 and to another recently discovered Drosophila TAF, dTAF(II)24. PDS and dTAF(II)24 do not interact, however, thus establishing a functional difference between these dTAFs. The PDS-dTAF(II)16 interaction is mediated by the HFD motif in PDS and the N terminus in dTAF(II)16, as indicated by yeast two-hybrid assays with protein fragments. Luciferase-reported transcription tests in transfected cells show that PDS or an HFD-containing fragment activates transcription only with the help of dTAF(II)16 and TBP. Consistent with this, the eye phenotype of flies expressing a sev-Ras1 construct is modulated by PDS and dTAF(II)16 in a gene dosage-dependent manner. Finally, we show that PDS function is required for cell viability in somatic mosaics. These findings indicate that PDS is a novel transcriptional coactivator that associates with a member of the general transcription factor TFIID. Instituto Cajal, C.S.I.C., Madrid 28002, Spain. Hernández-Hernández A A Ferrús A A eng GENBANK AJ237968 AJ276419 Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Insect Proteins 0 RNA, Messenger 0 Recombinant Fusion Proteins 0 Taf16 protein, Drosophila 0 Trans-Activators 0 Transcription Factor TFIID 0 Transcription Factors 0 Transcription Factors, TFII 0 prodos protein IM Amino Acid Sequence Animal Cell Survival Conserved Sequence Drosophila melanogaster chemistry embryology genetics metabolism Eye ultrastructure Female Gene Expression Regulation, Developmental In Situ Hybridization Insect Proteins chemistry genetics metabolism Microscopy, Electron, Scanning Molecular Sequence Data Phenotype Protein Binding RNA, Messenger genetics metabolism Recombinant Fusion Proteins Sequence Alignment Support, Non-U.S. Gov't Trans-Activation (Genetics) Trans-Activators chemistry genetics metabolism Transcription Factor TFIID Transcription Factors chemistry genetics metabolism Transcription Factors, TFII chemistry metabolism Two-Hybrid System Techniques FBrf0088383 96189330 8625792 1996 06 21 1996 06 21 2001 11 02

0950-1991 122 2 1996 Feb Two distinct roles for Ras in a developmentally regulated cell migration. 409-18 Receptor tyrosine kinases have been shown to promote cell movement in a variety of systems. The Ras protein, a well-documented downstream effector for receptor tyrosine kinases, may contribute to receptor tyrosine kinase-mediated motility. In the present study, we have examined the role of Ras in the migration of a small subset of follicle cells, known as the border cells, during Drosophila oogenesis. A dominant-negative Ras protein inhibited cell migration when expressed specifically in border cells during the period when these cells normally migrate. When expressed prior to migration, dominant-negative Ras promoted premature initiation of migration. Conversely, expression of constitutively active Ras prior to migration resulted in a significant delay in the initiation step. Furthermore, the defect in initiation of border cell migration found in slbo1, a mutation at the locus that encodes Drosophila C/EBP, was largely rescued by reducing Ras activity in border cells prior to migration. Taken together, these observations indicate that Ras activity plays two distinct roles in the border cells: (1) reduction in Ras activity promotes the initiation of that migration process and (2) Ras activity is required during border cell migration. We further examined the possible involvement of two downstream effectors of Ras in border cell migration. Raf activity was dispensable to border cell migration while reduced Ral activity inhibited initiation. We therefore suggest that Ras plays a critical role in the dynamic regulation of border cell migration via a Raf-independent pathway. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Lee T T Feig L L Montell D J DJ eng R29GM46425 GM NIGMS Journal Article

ENGLAND Development 8701744 0 CCAAT-Enhancer-Binding Proteins 0 DNA-Binding Proteins 0 Heat-Shock Proteins 0 Nuclear Proteins 0 Recombinant Proteins 0 Transcription Factors EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 3.2.1.23 beta-Galactosidase EC 3.6.1.- ras Proteins IM Animal Animals, Genetically Modified CCAAT-Enhancer-Binding Proteins Cell Movement DNA-Binding Proteins genetics metabolism Drosophila melanogaster physiology Female Genes, ras Heat-Shock Proteins biosynthesis metabolism Mutagenesis Nuclear Proteins genetics metabolism Oogenesis Ovary physiology Receptor Protein-Tyrosine Kinases metabolism Recombinant Proteins metabolism Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics beta-Galactosidase analysis biosynthesis ras Proteins metabolism FBrf0098298 97410312 9267027 1997 09 08 1997 09 08 2001 11 02

0092-8674 90 3 1997 Aug 8 Photoreceptor cell differentiation requires regulated proteolysis of the transcriptional repressor Tramtrack. 469-78 The transcription repressor Tramtrack (TTK) is found in cone cells but not photoreceptor cells of the Drosophila eye. We show that down-regulation of TTK expression occurs in photoreceptor cells and is required for their fate determination. Down-regulation requires the presence of Phyllopod (PHYL), which is induced by the RAS pathway, and Seven In Absentia (SINA). Loss of either gene causes accumulation of TTK in photoreceptor cells, and TTK does not accumulate in cone cells if both PHYL and SINA are present. We report that SINA and PHYL promote ubiquitination and rapid degradation of TTK by the proteasome pathway in cell culture, and both SINA and PHYL bind to the N-terminal domain of TTK. These results argue that photoreceptor differentiation is regulated by the RAS pathway through targeted proteolysis of the TTK repressor. Department of Biological Sciences, University of Pittsburgh, Pennsylvania 15260, USA. Li S S Li Y Y Carthew R W RW Lai Z C ZC eng EY10111 EY NEI Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins 0 Multienzyme Complexes 0 Nuclear Proteins 0 Recombinant Proteins 0 Transcription Factors 0 Ubiquitins 0 phyllopod protein 0 seven in absentia protein 0 tramtrack protein EC 3.4.22 Cysteine Endopeptidases EC 3.4.99.46 multicatalytic endopeptidase complex EC 3.6.1.- ras Proteins IM Animal Animals, Genetically Modified Cell Differentiation Cells, Cultured Cysteine Endopeptidases metabolism DNA-Binding Proteins biosynthesis metabolism Drosophila melanogaster Gene Expression Regulation, Developmental Genes, Insect Multienzyme Complexes metabolism Nuclear Proteins biosynthesis metabolism Photoreceptors, Invertebrate cytology physiology Recombinant Proteins biosynthesis metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Transfection Ubiquitins metabolism ras Proteins metabolism FBrf0102025 98192533 9524274 1998 05 13 1998 05 13 2000 12 18

0378-1119 209 1-2 1998 Mar 16 An enhancer region within the copia untranslated leader contains binding sites for Drosophila regulatory proteins. 239-46 The untranslated leader region (ULR) of the Drosophila LTR retrotransposon copia is known to be critical to the element's expression in a variety of species. Two copia ULR size variants are prevalent in natural populations. The more transcriptionally active full length variants contain within their ULRs two tandemly repeated copies of a 28-bp region of dyad symmetry with a sequence similarity to the core sequence of the SV40 enhancer. The region of dyad symmetry contains two inverted repeats of a 8-bp motif (TTGTGAAA) that occurs at three additional locations within the ULR. The less active ULR gap variants differ from full length variants in that they contain only one copy of the 28-bp sequence. We show that the full length copia ULR in either orientation but not the gap ULR can significantly enhance expression of a minimal hsp 70 promoter. We demonstrate by EMSA that the full length ULR, the gap ULR and the 28-bp sequence are each capable of binding the Drosophila CCAAT/enhancer binding protein (DmC/EBP) and another previously uncharacterized factor, copia binding factor-1 (CBF-1). Another Drosophila protein previously implicated in fat body specific expression of the alcohol dehydrogenase gene (Adh), the Box-B-binding factor-2 (BBF-2), is also shown to bind to the copia ULR. Department of Genetics, University of Georgia, Athens, GA 30602, USA. Wilson S S Matyunina L V LV McDonald J F JF eng Journal Article

NETHERLANDS Gene 7706761 0 DNA-Binding Proteins 0 Recombinant Fusion Proteins 0 Retroelements EC 2.3.1.28 Chloramphenicol O-Acetyltransferase IM Animal Base Sequence Binding Sites Cell Line Cell Nucleus metabolism Chloramphenicol O-Acetyltransferase biosynthesis DNA-Binding Proteins metabolism Drosophila melanogaster genetics metabolism Embryo, Nonmammalian metabolism Enhancer Elements (Genetics) Female Genes, Reporter Molecular Sequence Data Recombinant Fusion Proteins biosynthesis Repetitive Sequences, Nucleic Acid Retroelements Support, U.S. Gov't, Non-P.H.S. Transfection FBrf0048190 89137921 3147217 1989 04 04 1989 04 04 2000 12 18

0016-6731 120 4 1988 Dec Requirements for hedgehod, a segmental polarity gene, in patterning larval and adult cuticle of Drosophila. 1061-72 Mutations of the hedgehod gene are generally embryonic lethal, resulting in a lawn of denticles on the ventral surface. In strong alleles, no segmentation is obvious and the anteroposterior polarity of ventral denticles is lost. Temperature shift analysis of a temperature-sensitive allele indicates an embryonic activity period for hedgehod between 2.5 and 6 hr of embryonic development (at 25 degrees) and a larval/pupal period from 4 to 7 days of development (at 25 degrees). Mosaic analysis of hedgehod mutations in the adult cuticle indicates a series of defined defects associated with the failure of appropriate hedgehod expression. In particular, defects in the distal portions of the legs and antenna occur in association with homozygous hedgehog clones in the posterior compartment of those structures. Because the defects are associated with homozygous clones, but are not co-extensive, a type of "domineering" nonautonomy is proposed for the activity of the hedgehog gene. Department of Biological Sciences, Barnard College, New York, New York 10027. Mohler J J eng Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Drosophila melanogaster anatomy & histology embryology genetics Genes, Structural Larva anatomy & histology genetics growth & development Mosaicism Mutation Phenotype Support, U.S. Gov't, P.H.S. Temperature FBrf0044940 86281707 2426456 1986 09 25 1986 09 25 2000 12 18

0022-2836 188 4 1986 Apr 20 Interspecific nucleotide sequence comparisons used to identify regulatory and structural features of the Drosophila hsp82 gene. 499-515 We have sequenced the hsp82 heat shock gene and 5'-flanking DNA of four species of Drosophila in order to identify conserved features of possible regulatory significance and to determine the nature and rate of evolutionary change in various domains of the gene. All conserved sequences identified in the 5' non-transcribed region of the hsp82 gene of melanogaster, simulans, pseudoobscura and virilis lie within 150 base-pairs of the RNA initiation site. These include a 34 base-pair imperfect but highly conserved dyad made up of three overlapping copies of the consensus heat shock regulatory sequence dyad made up of three overlapping copies of the consensus heat shock regulatory sequence C-T-N-G-A-A-N-N-T-T-C-N-A-G. Several other highly conserved features are also seen. In pseudoobscura only, the region from -21 to -133 is almost exactly repeated 698 base-pairs upstream. The upstream repeat retains all of the sequences common to the four species in the -21 to -133 interval except for the T-A-T-A motif. One possibility is that this upstream sequence is involved in dosage compensation of the hsp82 gene, which is pseudoobscura is on the X chromosome. In melanogaster, simulans and virilis there is an oppositely oriented, non-heat shock gene 0.6 to 0.8 kb (kb = 10(3) base-pairs) upstream from the hsp82 transcription initiation site. Comparisons of the hsp82 transcription unit from the distantly related species show little or no sequence conservation in the intron and non-translated exon I sequences. In contrast, the coding regions of these species are 90% homologous at the DNA level and 97 to 99% identical at the amino acid level. Half of the amino acid changes have occurred within a 15-amino acid region that lies within an unusually polar domain of hsp82. From the sequence comparisons, we estimate the rate of silent (synonymous) site substitution in Drosophila as 1 X 10(-8)/nucleotide site per year, similar to that for mammals. Blackman R K RK Meselson M M eng GENBANK X03810 X03811 X03813 Journal Article

ENGLAND J Mol Biol 2985088R 0 Heat-Shock Proteins 63231-63-0 RNA 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Comparative Study DNA genetics Drosophila genetics Drosophila melanogaster genetics Genes Genes, Regulator Genes, Structural Heat-Shock Proteins genetics RNA genetics Repetitive Sequences, Nucleic Acid Sequence Homology, Nucleic Acid Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0128793 20145650 10679430 2000 03 22 2000 03 22 2000 12 18

0959-4388 10 1 2000 Feb Vnd/nkx, ind/gsh, and msh/msx: conserved regulators of dorsoventral neural patterning? 63-71 Expression of vnd in ventral, ind in intermediate, and msh in dorsal columns of fly neurectoderm, and of homologous gene families in corresponding domains of vertebrate neurectoderm, suggests that elements of dorsoventral neural patterning have been evolutionarily conserved. However, upstream signaling pathways regulating this columnar gene expression pattern appear to have diverged significantly throughout evolution. In addition, while recent loss-of-function studies in flies and mice indicate that these three genes may have a conserved role in regional specification, there is no obvious conservation of the particular cell fates deriving from corresponding domains. The three-column expression pattern may thus represent a developmental mechanism that is more resistant to evolutionary changes than genetic events upstream or downstream of it. Institute of Neuroscience, Eugene, 97403, USA. cornell@uoneuro. uoregon.edu. Cornell R A RA Ohlen T V TV eng HD22486 HD NICHD NS 23915 NS NINDS NS10119 NS NINDS Journal Article Review Review, Tutorial

ENGLAND Curr Opin Neurobiol 9111376 0 Homeodomain Proteins 0 NK-2 protein 0 intermediate neuroblasts defective protein 0 muscle segment homeobox protein IM Animal Body Patterning Central Nervous System cytology embryology metabolism Conserved Sequence genetics physiology Drosophila melanogaster Gene Expression Regulation, Developmental Homeodomain Proteins genetics physiology Signal Transduction Support, U.S. Gov't, P.H.S. Vertebrates 79 FBrf0131403 20530667 11076972 2000 12 22 2000 12 22 2003 06 16

0021-9525 151 4 2000 Nov 13 Apical, lateral, and basal polarization cues contribute to the development of the follicular epithelium during Drosophila oogenesis. 891-904 Analysis of the mechanisms that control epithelial polarization has revealed that cues for polarization are mediated by transmembrane proteins that operate at the apical, lateral, or basal surface of epithelial cells. Whereas for any given epithelial cell type only one or two polarization systems have been identified to date, we report here that the follicular epithelium in Drosophila ovaries uses three different polarization mechanisms, each operating at one of the three main epithelial surface domains. The follicular epithelium arises through a mesenchymal-epithelial transition. Contact with the basement membrane provides an initial polarization cue that leads to the formation of a basal membrane domain. Moreover, we use mosaic analysis to show that Crumbs (Crb) is required for the formation and maintenance of the follicular epithelium. Crb localizes to the apical membrane of follicle cells that is in contact with germline cells. Contact to the germline is required for the accumulation of Crb in follicle cells. Discs Lost (Dlt), a cytoplasmic PDZ domain protein that was shown to interact with the cytoplasmic tail of Crb, overlaps precisely in its distribution with Crb, as shown by immunoelectron microscopy. Crb localization depends on Dlt, whereas Dlt uses Crb-dependent and -independent mechanisms for apical targeting. Finally, we show that the cadherin-catenin complex is not required for the formation of the follicular epithelium, but only for its maintenance. Loss of cadherin-based adherens junctions caused by armadillo (beta-catenin) mutations results in a disruption of the lateral spectrin and actin cytoskeleton. Also Crb and the apical spectrin cytoskeleton are lost from armadillo mutant follicle cells. Together with previous data showing that Crb is required for the formation of a zonula adherens, these findings indicate a mutual dependency of apical and lateral polarization mechanisms. Department of Zoology, University of Toronto, Toronto, Ontario, Canada M5S 3G5. Tanentzapf G G Smith C C McGlade J J Tepass U U eng Journal Article

UNITED STATES J Cell Biol 0375356 0 Insect Proteins 0 Membrane Proteins 0 crb protein, Drosophila 0 discs lost protein, Drosophila IM Amino Acid Sequence Animal Cell Differentiation Cell Polarity Drosophila melanogaster physiology Epithelial Cells cytology physiology Female Insect Proteins analysis chemistry metabolism Membrane Proteins analysis metabolism Mesoderm cytology physiology Molecular Sequence Data Oogenesis physiology Ovarian Follicle cytology physiology Support, Non-U.S. Gov't FBrf0087044 96386245 8791421 1996 10 24 1996 10 24 2000 12 18

0955-0674 8 2 1996 Apr Recent advances in understanding signal transduction pathways in worms and flies. 231-8 One major challenge in the fields of signal transduction and pattern formation is to understand how multiple signals are integrated to determine cell fates. Two developmental systems, vulval development in Caenorhabditis elegans and axis formation during Drosophila melanogaster oogenesis, require the epidermal growth factor receptor tyrosine kinase and the NOTCH signaling pathways to specify cell fates. Current work in both systems has provided new opportunities to investigate the potential for the cross-talk between these different signaling pathways. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Alpert Building, 200 Longwood Avenue, Boston, MA 02115, USA. Duffy J B JB Perrimon N N eng Journal Article Review Review, Tutorial

UNITED STATES Curr Opin Cell Biol 8913428 0 Membrane Proteins 0 Receptors, Invertebrate Peptide 0 epidermal growth factor receptor homolog, Drosophila 0 notch protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Caenorhabditis elegans physiology Drosophila melanogaster physiology Female Forecasting Human Membrane Proteins metabolism Oocytes Receptor, Epidermal Growth Factor metabolism Receptors, Invertebrate Peptide metabolism Signal Transduction physiology 44 FBrf0041355 85264024 6443124 1985 09 19 1985 09 19 2000 12 18

0167-7063 1 4 1984 Dec The expression of neurogenic loci in imaginal epidermal cells of Drosophila melanogaster. 315-32 Six zygotically expressed genomic loci of Drosophila melanogaster, N, bib, mam, neu, Dl and E (spl), have previously been found to be involved in the commitment of ectodermal cells as neuroblasts. We have studied phenotypes induced by various mutant alleles at these 6 loci in imaginal epidermal cells, in order to assess possible implications of the genes in functions other than early neurogenesis. When homozygous, any of these mutations except bib affected the development of bristles and compound eye in various ways. These range from cell death to the production of additional bristles and several defects in ommatidial patterning, depending on the allele used. In contrast clones of bib homozygous cells exhibited wild-type phenotypes. The differences found in the expression of the neurogenic genes are discussed with respect to a hypothesis on the genetic control of neurogenesis. Dietrich U U Campos-Ortega J A JA eng Journal Article

NETHERLANDS J Neurogenet 8406473 IM Alleles Animal Cell Count Clone Cells physiology ultrastructure Drosophila melanogaster anatomy & histology genetics Epidermis cytology physiology Eye growth & development ultrastructure Female Male Mutation Neurons physiology Phenotype Support, Non-U.S. Gov't Temperature FBrf0045753 87187612 3105892 1987 05 29 1987 05 29 2000 12 18

0092-8674 49 2 1987 Apr 24 Autonomous requirements for the segment polarity gene armadillo during Drosophila embryogenesis. 177-84 Embryos hemizygous for armadillo produce a "segment polarity" phenotype in which the naked posterior two-thirds of each segment is replaced by denticles with reversed polarity. Small patches of homozygous arm cells induced by mitotic recombination also form such denticles, indicating that the changes in cellular fate observed in homozygous arm embryos are autonomous at the level of single cells. Clonally derived arm patches do not, however, show the characteristic arm polarity reversals, arguing that this feature of the phenotype depends on cell interactions in fully mutant embryos. Few, if any, clones were found in the posterior-most regions of the naked cuticle, and none were found in the posterior compartments of the thorax. Wieschaus E E Riggleman R R eng HD15587 HD NICHD Journal Article

UNITED STATES Cell 0413066 IM Animal Clone Cells cytology Drosophila melanogaster embryology genetics Gene Expression Regulation Morphogenesis Phenotype Skin Support, U.S. Gov't, P.H.S. FBrf0132263 20578813 11136981 2001 01 10 2001 01 25 2003 06 16

0092-8674 103 6 2000 Dec 8 Dpp gradient formation in the Drosophila wing imaginal disc. 971-80 The secreted signaling protein Dpp acts as a morphogen to pattern the anterior-posterior axis of the Drosophila wing. Dpp activity is required in all cells of the developing wing imaginal disc, but the ligand gradient that supports this activity has not been characterized. Here we make use of a biologically active form of Dpp tagged with GFP to examine the ligand gradient. Dpp-GFP forms an unstable extracellular gradient that spreads rapidly in the wing disc. The activity gradient visualized by MAD phosphorylation differs in shape from the ligand gradient. The pMAD gradient adjusted to compartment size when this was experimentally altered. These observations suggest that the Dpp activity gradient may be shaped at the level of receptor activation. European Molecular Biology Laboratory Meyerhofstr 1 69117, Heidelberg, Germany. Teleman A A AA Cohen S M SM eng Journal Article

UNITED STATES Cell 0413066 0 Homeodomain Proteins 0 Insect Proteins 0 Ligands 0 Luminescent Proteins 0 Receptors, Cell Surface 0 Recombinant Fusion Proteins 0 Transcription Factors 0 brinker protein, Drosophila 0 dpp protein, Drosophila 0 sal protein 147336-22-9 green fluorescent protein EC 2.7.1.- DTFR protein, Drosophila EC 2.7.1.137 1-Phosphatidylinositol 3-Kinase EC 2.7.1.37 Protein-Serine-Threonine Kinases IM 1-Phosphatidylinositol 3-Kinase metabolism Animal Body Patterning genetics Cells, Cultured Drosophila melanogaster genetics growth & development physiology Genes, Reporter Homeodomain Proteins genetics metabolism Immunoblotting Insect Proteins genetics metabolism Ligands Luminescent Proteins genetics metabolism Microscopy, Confocal Protein Transport physiology Protein-Serine-Threonine Kinases metabolism Receptors, Cell Surface metabolism Recombinant Fusion Proteins metabolism Support, Non-U.S. Gov't Time Factors Transcription Factors genetics metabolism Wing chemistry growth & development metabolism FBrf0130066 20411175 10952897 2000 11 15 2000 11 15 2002 12 26

0950-1991 127 18 2000 Sep High bicoid levels render the terminal system dispensable for Drosophila head development. 3993-9 In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis while the ends of the embryo are patterned by the maternal terminal system. At the posterior pole, expression of terminal gap genes is mediated by the local activation of the Torso receptor tyrosine kinase (Tor). At the anterior, terminal gap genes are also activated by the Tor pathway but Bcd contributes to their activation. Here we present evidence that Tor and Bcd act independently on common target genes in an additive manner. Furthermore, we show that the terminal maternal system is not required for proper head development, since high levels of Bcd activity can functionally rescue the lack of terminal system activity at the anterior pole. This observation is consistent with a recent evolution of an anterior morphogenetic center consisting of Bcd and anterior Tor function. Department of Biology, New York University, New York NY 10003 USA. Schaeffer V V Killian D D Desplan C C Wimmer E A EA eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Hkb protein 0 Homeodomain Proteins 0 Insect Proteins 0 RNA, Messenger 0 Trans-Activators 0 bicoid protein, Drosophila EC 2.7.1.- TOR protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM Animal Animals, Genetically Modified Body Patterning genetics DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology enzymology genetics Evolution, Molecular Female Gene Expression Regulation, Developmental Head embryology Homeodomain Proteins genetics metabolism Immunohistochemistry In Situ Hybridization Insect Proteins genetics metabolism Mutation Phenotype RNA, Messenger genetics metabolism Receptor Protein-Tyrosine Kinases genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Trans-Activators genetics metabolism Transgenes genetics FBrf0048952 89042140 3141923 1988 12 09 1988 12 09 2000 12 18

0027-8424 85 21 1988 Nov Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. 8136-40 Two genes known to control the determination of segmental identity in Drosophila melanogaster are polycomb and antennapedia. To identify additional genes involved in the determination of segmental identity, we have isolated dominant modifers (both suppressors and enhancers) of polycomb and/or antennapedia mutations. Sixty-four such modifier mutations have been recovered and mapped to 18 complementation groups. All of the mutations identify genes necessary for viability of the zygote. Six of the 18 genes that were identified by mutations that interact with polycomb and/or antennapedia have been previously characterized as homoeotic genes [i.e., Sex combs reduced (Scr), Brista (Ba), trithorax (trx), Polycomb (Pc), Polycomblike (Pcl), and Sex comb on midleg (Scm)]. Mutations in several of the additional loci identified here have also been shown to have homoeotic phenotypes. Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892. Kennison J A JA Tamkun J W JW eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 IM Animal Chromosome Mapping Drosophila melanogaster genetics Enhancer Elements (Genetics) Mutation Phenotype Support, Non-U.S. Gov't Suppression, Genetic Zygote FBrf0152011 22269290 12381666 2002 10 16 2002 11 14

0890-9369 16 20 2002 Oct 15 A cellular memory module conveys epigenetic inheritance of hedgehog expression during Drosophila wing imaginal disc development. 2672-83 In Drosophila, the Trithorax-group (trxG) and Polycomb-group (PcG) proteins interact with chromosomal elements, termed Cellular Memory Modules (CMMs). By modifying chromatin, this ensures a stable heritable maintenance of the transcriptional state of developmental regulators, like the homeotic genes, that is defined embryonically. We asked whether such CMMs could also control expression of genes involved in patterning imaginal discs during larval development. Our results demonstrate that expression of the hedgehog gene, once activated, is maintained by a CMM. In addition, our experiments indicate that the switching of such CMMs to an active state during larval stages, in contrast to embryonic stages, may require specific trans-activators. Our results suggest that the patterning of cells in particular developmental fields in the imaginal discs does not only rely on external cues from morphogens, but also depends on the previous history of the cells, as the control by CMMs ensures a preformatted gene expression pattern. Zentrum für Molekulare Biologie Heidelberg (ZMBH), University of Heidelberg, D-69120 Heidelberg, Germany. Maurange Cédric C Paro Renato R eng Journal Article

United States Genes Dev 8711660 0 Chromatin 0 DNA Primers 0 DNA-Binding Proteins 0 Drosophila Proteins 0 RNA, Messenger 0 trithorax gene product 134549-01-2 Polycomb protein, insect 149291-21-4 hedgehog protein, Drosophila IM Animal Animals, Genetically Modified Cell Division physiology Chromatin genetics DNA Primers chemistry DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics Drosophila melanogaster genetics growth & development Embryo, Nonmammalian Gene Expression Regulation, Developmental In Situ Hybridization Larva cytology Memory physiology Polymerase Chain Reaction Precipitin Tests RNA, Messenger metabolism Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't Trans-Activation (Genetics) Wing cytology FBrf0133206 21062670 11102824 2001 01 26 2001 07 05 2002 11 05

0960-9822 10 22 2000 Nov 16 Insect metamorphosis: out with the old, in with the new. R830-3 During insect metamorphosis, the steroid hormone ecdysone activates programmed cell death of larval tissues and the further development of adult tissues. Recent studies suggest that the E93 gene is both necessary and sufficient to target tissues for ecdysone-induced apoptosis. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA. Buszczak M M Segraves W A WA eng Journal Article Review Review, Tutorial

England Curr Biol 9107782 0 CF1 protein 0 DNA-Binding Proteins 0 E74 protein, Drosophila 0 E93 protein, Drosophila 0 Insect Proteins 0 Neuropeptides 0 Peptides 0 Receptors, Steroid 0 Transcription Factors 0 broad-complex protein, Drosophila 0 ecdysone receptor 0 head involution defective protein 0 inhibitor of apoptosis 2, Drosophila 0 reaper peptide, Drosophila 0 transcription factor E75, Manduca 5289-74-7 Ecdysterone IM Animal Apoptosis DNA-Binding Proteins genetics metabolism Drosophila melanogaster genetics physiology Ecdysterone metabolism pharmacology Gene Expression Regulation Insect Proteins genetics physiology Metamorphosis, Biological physiology Neuropeptides genetics Peptides genetics Receptors, Steroid metabolism Transcription Factors genetics metabolism physiology 21 FBrf0152056 22166128 12176927 2002 08 14 2002 09 06

1088-9051 12 8 2002 Aug B-ZIP proteins encoded by the Drosophila genome: evaluation of potential dimerization partners. 1190-200 The basic region-leucine zipper (B-ZIP) (bZIP) protein motif dimerizes to bind specific DNA sequences. We have identified 27 B-ZIP proteins in the recently sequenced Drosophila melanogaster genome. The dimerization specificity of these 27 B-ZIP proteins was evaluated using two structural criteria: (1) the presence of attractive or repulsive interhelical g<-->e' electrostatic interactions and (2) the presence of polar or charged amino acids in the 'a' and 'd' positions of the hydrophobic interface. None of the B-ZIP proteins contain only aliphatic amino acids in the'a' and 'd' position. Only six of the Drosophila B-ZIP proteins contain a "canonical" hydrophobic interface like the yeast GCN4, and the mammalian JUN, ATF2, CREB, C/EBP, and PAR leucine zippers, characterized by asparagine in the second 'a' position. Twelve leucine zippers contain polar amino acids in the first, third, and fourth 'a' positions. Circular dichroism spectroscopy, used to monitor thermal denaturations of a heterodimerizing leucine zipper system containing either valine (V) or asparagine (N) in the 'a' position, indicates that the V-N interaction is 2.3 kcal/mole less stable than an N-N interaction and 5.3 kcal/mole less stable than a V-V interaction. Thus, we propose that the presence of polar amino acids in novel positions of the 'a' position of Drosophila B-ZIP proteins has led to leucine zippers that homodimerize rather than heterodimerize. Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20814, USA. Fassler Jan J Landsman David D Acharya Asha A Moll Jonathan R JR Bonovich Maria M Vinson Charles C eng Journal Article

United States Genome Res 9518021 0 Amino Acids 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Transcription Factors 0 bZIP enhancer protein 7004-03-7 Valine 7006-34-0 Asparagine IM Genome Res. 2002 Aug;12(8):1156-8 12176922 Amino Acid Sequence Amino Acids chemistry Animal Asparagine metabolism Comparative Study DNA-Binding Proteins genetics Databases, Protein Dimerization Drosophila Proteins chemistry genetics Drosophila melanogaster genetics Genes, Structural, Insect Genome Human Leucine Zippers genetics Molecular Sequence Data Phylogeny Protein Interaction Mapping methods Protein Structure, Tertiary genetics Sequence Alignment methods Sequence Homology, Amino Acid Surface Properties Transcription Factors genetics Valine metabolism FBrf0086416 97002546 8849893 1996 12 06 1996 12 06 2000 12 18

0016-6731 142 3 1996 Mar Cytoplasmic dynein function is essential in Drosophila melanogaster. 865-78 The microtubule motor cytoplasmic dynein has been implicated in a variety of intracellular transport processes. We previously identified and characterized the Drosophila gene Dhc64C, which encodes a cytoplasmic dynein heavy chain. To investigate the function of the cytoplasmic dynein motor, we initiated a mutational analysis of the Dhc64C dynein gene. A small deletion that removes the chromosomal region containing the heavy chain gene was used to isolate EMS-induced lethal mutations that define at least eight essential genes in the region. Germline transformation with a Dhc64C transgene rescued 16 mutant alleles in the single complementation group that identifies the dynein heavy chain gene. All 16 alleles were hemizygous lethal, which demonstrates that the cytoplasmic dynein heavy chain gene Dhc64C is essential for Drosophila development. Furthermore, our failure to recover somatic clones of cells homozygous for a Dhc64C mutation indicates that cytoplasmic dynein function is required for cell viability in several Drosophila tissues. The intragenic complementation of dynein alleles reveals multiple mutant phenotypes including male and/or female sterility, bristle defects, and defects in eye development. Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108, USA. Gepner J J Li M M Ludmann S S Kortas C C Boylan K K Iyadurai S J SJ McGrail M M Hays T S TS eng 5T32-07323 PHS GM-17485 GM NIGMS GM-44757 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 3.6.1.33 Dynein ATPase IM Alleles Animal Cytoplasm metabolism Drosophila melanogaster genetics growth & development Dynein ATPase genetics Female Gene Expression Regulation Genes, Insect Genetic Complementation Test Larva Male Mutation Pupa Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transformation, Genetic Zygote FBrf0102616 98298924 9635185 1998 09 16 1998 09 16 2000 12 18

0960-9822 8 11 1998 May 21 Integrins: a role for adhesion molecules in olfactory memory. R386-9 A gene required for short-term memory in Drosophila, Volado, encodes an alpha integrin and is preferentially expressed in the mushroom bodies of the adult brain. Adhesion molecules of this kind may play a role in olfactory memory by altering the strength of synaptic connections in an experience-dependent manner. Cold Spring Harbor Laboratory, New York 11724, USA. Connolly J B JB Tully T T eng HD 32245 HD NICHD HD 33098 HD NICHD NS 34480 NS NINDS Journal Article Review Review, Tutorial

ENGLAND Curr Biol 9107782 0 Integrins IM Animal Brain physiology Drosophila melanogaster genetics physiology Gene Expression Genes, Insect Integrins genetics physiology Memory physiology Smell physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 28 FBrf0132053 20558917 11104525 2000 12 15 2001 01 04 2003 01 03

1465-6914 1 1 2000 Fly immunity: great expectations. REVIEWS106 Preliminary analysis of the Drosophila genome sequence reveals important similarities and differences between the functioning of mammalian and invertebrate immune systems. Yale University School of Medicine, New Haven, CT 06520, USA. ruslan.medzhitov@yale.edu Medzhitov R R Janeway Jr C C eng Journal Article Review Review, Tutorial 2000 06 09

ENGLAND Genome Biol 100960660 IM Animal Drosophila melanogaster genetics immunology Genome Human 17 FBrf0106206 99114022 9916984 1999 02 16 1999 02 16 2003 02 03

0950-9232 17 25 1998 Dec 24 Mechanisms and control of programmed cell death in invertebrates. 3215-23 Apoptosis is a morphologically distinct form of programmed cell death that plays important roles in development, tissue homeostasis and a wide variety of diseases, including cancer, AIDS, stroke, myopathies and various neurodegenerative disorders (see Thompson (1995) for review). It is now clear that apoptosis occurs by activating an intrinsic cell suicide program which is constitutively expressed in most animal cells, and that key components of this program have been conserved in evolution from worms to insects to man. Genetic studies of programmed cell death in experimentally highly accessible invertebrate model systems have provided important clues about the molecular nature of the death program, and the intracellular mechanisms that control its activation. This review summarizes some of the key findings in this area, but also touches on some of the many unresolved questions and challenges that remain. Massachusetts Institute of Technology, Howard Hughes Medical Institute, Department of Biology, Cambridge 02139, USA. Bergmann A A Agapite J J Steller H H eng Journal Article Review Review, Tutorial

ENGLAND Oncogene 8711562 0 Insect Proteins 0 Neuropeptides 0 Peptides 0 grim protein, Drosophila 0 head involution defective protein 0 reaper peptide, Drosophila EC 3.4.22.- Caspases IM Animal Apoptosis genetics Caenorhabditis elegans physiology Caspases physiology Cell Survival physiology Drosophila melanogaster physiology Genes, ras physiology Insect Proteins physiology Invertebrates physiology Neuropeptides physiology Peptides physiology Support, Non-U.S. Gov't 130 FBrf0101887 98151515 9482888 1998 04 09 1998 04 09 2000 12 18

0027-8424 95 5 1998 Mar 3 Protein kinase A directly regulates the activity and proteolysis of cubitus interruptus. 2349-54 Cubitus interruptus (Ci) is a transcriptional factor that is positively regulated by the hedgehog (hh) signaling pathway. Recent work has shown that a 75-kDa proteolytic product of the full-length CI protein translocates to the nucleus and represses the transcription of CI target genes. In cells that receive the hh signal, the proteolysis of CI is inhibited and the full-length protein can activate the hh target genes. Because protein kinase A (PKA) inhibits the expression of the hh target genes in developing embryos and discs and the loss of PKA activity results in elevated levels of full-length CI protein, PKA might be involved directly in the regulation of CI proteolysis. Here we demonstrate that the PKA pathway antagonizes the hh pathway by phosphorylating CI. We show that the PKA-mediated phosphorylation of CI promotes its proteolysis from the full-length active form to the 75-kDa repressor form. The PKA catalytic subunit increases the proteolytic processing of CI and the PKA inhibitor, PKI, blocks the processing. In addition, cells do not process the CI protein to the 75-kDa repressor when all of the PKA sites in CI are mutated. Mutant CI proteins that cannot be phosphorylated by PKA have increased transcriptional activity compared with wild-type CI. In addition, exogenous PKA can increase further the transcriptional activity of the CI mutant, suggesting that PKA has a second positive, indirect effect on CI activity. In summary, we show that the modulation of the hh signaling pathway by PKA occurs directly at the level of CI phosphorylation. Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA. Chen Y Y Gallaher N N Goodman R H RH Smolik S M SM eng DK44239 DK NIDDK Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA-Binding Proteins 0 Insect Proteins 0 Recombinant Proteins 0 cubitus interruptus protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Cell Line Cyclic AMP-Dependent Protein Kinases metabolism DNA-Binding Proteins biosynthesis metabolism Drosophila melanogaster Insect Proteins metabolism Kinetics Models, Biological Phosphorylation Recombinant Proteins biosynthesis metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics) Transfection Zinc Fingers FBrf0144790 21606134 11740932 2001 12 13 2002 01 14

1534-5807 1 6 2001 Dec Trachealess--a new transcription factor target for PKB/Akt. 726-8 Applying a combined genetic and biochemical approach has led to the identification of a new protein kinase B/Akt target, the transcription factor Trachealess. Signal Transduction Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom. Downward J J Leevers S J SJ eng Comment Journal Article

United States Dev Cell 101120028 0 Drosophila Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 proto-oncogene protein akt 0 trachealess protein EC 2.7.1.137 1-Phosphatidylinositol 3-Kinase EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Dev Cell. 2001 Dec;1(6):817-27 11740943 1-Phosphatidylinositol 3-Kinase metabolism Animal Drosophila Proteins genetics metabolism Drosophila melanogaster genetics growth & development metabolism Human Insect Proteins genetics metabolism Models, Biological Protein-Serine-Threonine Kinases metabolism Proto-Oncogene Proteins metabolism Signal Transduction physiology Transcription Factors genetics metabolism FBrf0051358 91084847 2124516 1991 02 01 1991 02 01 2000 12 18

0092-8674 63 6 1990 Dec 21 X:A ratio, the primary sex-determining signal in Drosophila, is transduced by helix-loop-helix proteins. 1179-91 Drosophila determines its sex by "counting" X chromosomes. We show that premature expression of the pair-rule segmentation gene hairy interferes with this process, resulting in female-specific lethality by inhibiting initiation of the master control gene Sex-lethal (Sxl). The female-specific lethality can be suppressed by a constitutive Sxl allele or by extra copies of X-linked "counting elements." These results are best explained by competition between hairy and other helix-loop-helix transcription factors that act in chromosome counting. We have confirmed this model by showing that misexpression of the achaete-scute T4 gene induces ectopic Sxl expression and male-specific lethality, confirming that achaete-scute T4 is the sisterless-b counting element. We propose that X chromosomes are counted through heterodimers of helix-loop-helix transcription factors that act synergistically to initiate Sxl expression. Zoology Department, University of Oxford, England. Parkhurst S M SM Bopp D D Ish-Horowicz D D eng Journal Article

UNITED STATES Cell 0413066 0 DNA-Binding Proteins IM Cell 1991 Mar 8;64(5):following 1046 Sxl Animal Blastoderm physiology Crosses, Genetic DNA-Binding Proteins metabolism Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Female Genes, Lethal Male Restriction Mapping Sex Determination (Analysis) Support, Non-U.S. Gov't Transduction, Genetic Transformation, Genetic X Chromosome FBrf0138356 21417201 11526071 2001 08 29 2001 10 11 2002 10 21

0950-1991 128 14 2001 Jul Redundant function of Runt Domain binding partners, Big brother and Brother, during Drosophila development. 2639-48 The Core Binding Factor is a heterodimeric transcription factor complex in vertebrates that is composed of a DNA binding alpha-subunit and a non-DNA binding beta-subunit. The alpha-subunit is encoded by members of the Runt Domain family of proteins and the beta-subunit is encoded by the CBF beta gene. In Drosophila, two genes encoding alpha-subunits, runt and lozenge, and two genes encoding beta-subunits, Big brother and Brother, have been previously identified. Here, a sensitized genetic screen was used to isolate mutant alleles of the Big brother gene. Expression studies show that Big brother is a nuclear protein that co-localizes with both Lozenge and Runt in the eye imaginal disc. The nuclear localization and stability of Big brother protein is mediated through the formation of heterodimeric complexes between Big brother and either Lozenge or Runt. Big brother functions with Lozenge during cell fate specification in the eye, and is also required for the development of the embryonic PNS. ds-RNA-mediated genetic interference experiments show that Brother and Big brother are redundant and function together with Runt during segmentation of the embryo. These studies highlight a mechanism for transcriptional control by a Runt Domain protein and a redundant pair of partners in the specification of cell fate during development. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Kaminker J S JS Singh R R Lebestky T T Yan H H Banerjee U U eng 2RO1EY08152 EY NEI GM07185 GM NIGMS Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Nuclear Proteins 0 Runt protein 0 Transcription Factors 0 big-brother protein 0 brother protein 0 lozenge protein, Drosophila IM Animal DNA-Binding Proteins genetics metabolism Drosophila melanogaster genetics growth & development metabolism physiology Enhancer Elements (Genetics) Eye growth & development metabolism Gene Expression Insect Proteins genetics metabolism physiology Nuclear Proteins genetics metabolism physiology Phenotype Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism physiology FBrf0042048 86079516 2416463 1986 01 29 1986 01 29 2000 12 18

0092-8674 43 1 1985 Nov Homeo box genes of the Antennapedia and bithorax complexes of Drosophila. 71-80 The Antennapedia, Ultrabithorax, and fushi tarazu genes of Drosophila melanogaster each contain a very similar protein coding sequence, the homeo box. Previously cloned homeo box sequences were used to isolate additional well conserved members of the homeo box gene family. The most strongly conserved members of the homeo box gene family map within either the Antennapedia or Bithorax gene complexes. The tissue distribution of transcripts encoded by the two rightmost homeo box genes of the Bithorax complex are compared with the iab-2 and iab-7 phenotypes. Regulski M M Harding K K Kostriken R R Karch F F Levine M M McGinnis W W eng GENBANK M12007 M12008 M12009 M21173 X05136 Journal Article

UNITED STATES Cell 0413066 63231-63-0 RNA IM Animal Chromosome Mapping Cloning, Molecular Drosophila melanogaster analysis embryology genetics Genes, Structural Morphogenesis Mutation Phenotype RNA analysis Repetitive Sequences, Nucleic Acid Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0049851 90034165 2509291 1989 12 21 1989 12 21 2000 12 18

0016-6723 54 1 1989 Aug Interaction of hairless, delta, enhancer of split and notch genes of Drosophila melanogaster as expressed in adult morphology. 23-6 The interaction of three neurogenic loci viz. Delta, Enhancer of split and Notch, and a related gene, Hairless, of Drosophila melanogaster was investigated at the adult morphology level by measuring the effects of the mutations of the three other genes on the expression of the recessive lethal antimorphic Abruptex mutations of the Notch locus. The Abruptex mutations were also coupled in cis or trans with facet-glossy or split mutations of the Notch locus. In some of the experiments, the genotype of the fly was homozygous for either facet-glossy or split mutation or their wild type alleles but heterozygous for the Abruptex. Facet-glossy is located in a large intron of the locus, whereas split is located in the same exon as Abruptex. In all compounds studied, Delta suppressed the expression of Abruptex while Hairless and Enhancer of split enhanced it. The interactions of the four genes studied were allele specific, suggesting an interaction at the protein level. The comparison of the results presented in this study on the interaction of the neurogenic genes with other results on the same subject suggests that the interactions are similar in embryonic and imaginal development. Sirén M M Portin P P eng Journal Article

ENGLAND Genet Res 0370741 IM Alleles Animal Drosophila melanogaster anatomy & histology genetics Gene Expression Regulation Genes Genotype Mutation Support, Non-U.S. Gov't FBrf0047948 89091138 3145197 1989 02 21 1989 02 21 2000 12 18

0261-4189 7 12 1988 Dec 1 Sex determination in Drosophila: the X-chromosomal gene liz is required for Sxl activity. 3889-98 In Drosophila, females require products of the gene Sxl for sex determination, dosage compensation and fertility. I show here that the X-chromosomal gene liz, located in 4F1 to 4F11 and previously called fs(1)1621, provides maternal and zygotic functions necessary for Sxl activity in germ line and soma. In XX animals, the mutation SxlM1 which was reported to express the female-specific functions of Sxl constitutively can rescue all phenotypes resulting from lack of liz product. XY animals carrying SxlM1 and lacking maternal or zygotic liz activity survive as males with some female traits. A stock was constructed in which the females are liz SxlM1/liz SxlM1 and males liz SxlM1/Y. This shows that SxlM1 is not truly expressed constitutively in animals with an X:A ratio of 0.5, but requires activity of liz for initiation or maintenance. Zoological Institute, University of Zürich, Switzerland. Steinmann-Zwicky M M eng Journal Article

ENGLAND EMBO J 8208664 IM Animal Chromosome Mapping Drosophila melanogaster genetics Epistasis, Genetic Gene Expression Regulation Genes, Structural Mutation Sex Determination (Analysis) Support, Non-U.S. Gov't X Chromosome FBrf0128671 20215490 10752030 2000 06 19 2000 06 19 2000 12 18

0016-6758 36 2 2000 Feb [Effect of genotypic environment on phenotypic manifestation of radius incompletus mutation in Drosophila melanogaster] 182-90 Genetic analysis of marked regions of Drosophila chromosome 3 was performed in order to localize the "effective factors" of the polygene system that controls the expression of the limiting mutation in radius incompletus, the major-effect gene. The marked homozygous strain with genotype th st ri sr ca was crossed with the "selection" riSN strain. Contributions of the marked regions of chromosome 3 to the expression of the proximal and distal fragments of the wing radial vein were estimated. It was demonstrated that the th-st region of the marked strain contained a polygene determining a large positive contribution to the lengths of both fragments, whereas the st-ri region contained a polygene determining a large negative contribution to the length of the distal fragment compared to the riSN strain. Crossings were performed between strains that contained Mendelian mutations of the ri, ve, and vn major-effect genes of the wing vein patterns. Unexpectedly, a strong, non-additive effect of the interaction between these mutations was found. This effect was expressed as a complete disarrangement of the wing vein pattern. Each participant gene may be regarded as a large-effect polygene relative to the other genes. Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia. Vasil'eva L A LA Ratner V A VA rus Journal Article Vliianie geneticheskoĭ sredy na kharakter fenotipicheskogo proiavleniia mutatsii radius incompletus u Drosophila melanogaster.

RUSSIA Genetika 0047354 0 Genetic Markers IM Animal Drosophila melanogaster genetics English Abstract Female Gene Expression Genetic Markers Male Mutation Phenotype FBrf0093467 97277268 9115398 1997 06 20 1997 06 20 2003 06 16

0960-9822 7 5 1997 May 1 Cytoplasmic flows localize injected oskar RNA in Drosophila oocytes. 326-37 BACKGROUND: The oskar (osk) gene encodes a determinant of posterior identity in Drosophila, and the localization of osk RNA to the pole plasm at the posterior pole of the oocyte is essential for development of the embryo. The mechanisms by which osk RNA is localized are unknown. RESULTS: To study the mechanisms underlying localization of osk RNA, we have injected fluorescently labelled RNA into oocytes at stages 9, 10 and 11. Injected osk RNA localizes to the pole plasm, reproducing localization of the endogenous RNA. In oocytes at stages 10 and 11, the long-range movement of injected osk RNA is promoted by a vigorous, microtubule-dependent cytoplasmic flow, or ooplasmic streaming. Treatment with colchicine, a microtubule-destabilizing drug, inhibits ooplasmic streaming and prevents localization of the RNA from an injection site distal to the posterior pole. If the RNA is injected close to the posterior pole, however, it localizes even in the presence of colchicine. Similarly, in small oocytes, such as stage 9 oocytes, localization of injected osk RNA is insensitive to colchicine. CONCLUSIONS: These results reveal that microtubule-dependent cytoplasmic flows could contribute to the long-range transport of osk RNA, whereas microtubule-independent processes could mediate short-range transport. These results also highlight the role of the osk RNA anchor in the localization process. Programme in Developmental Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, D-69117, Germany. Glotzer J B JB Saffrich R R Glotzer M M Ephrussi A A eng Journal Article

ENGLAND Curr Biol 9107782 0 Insect Proteins 0 oskar protein, Drosophila 63231-63-0 RNA 64-86-8 Colchicine IM Animal Colchicine pharmacology Drosophila melanogaster Genes, Insect Insect Proteins biosynthesis physiology Kinetics Microtubules drug effects physiology Oocytes cytology drug effects physiology Oogenesis RNA metabolism Support, Non-U.S. Gov't Transcription, Genetic FBrf0146988 21956348 11959829 2002 04 17 2002 06 03

0950-1991 129 9 2002 May Mosaic analyses reveal the function of Drosophila Ras in embryonic dorsoventral patterning and dorsal follicle cell morphogenesis. 2209-22 In Drosophila melanogaster, the Ras signal transduction pathway is the primary effector of receptor tyrosine kinases, which govern diverse developmental programs. During oogenesis, epidermal growth factor receptor signaling through the Ras pathway patterns the somatic follicular epithelium, establishing the dorsoventral asymmetry of eggshell and embryo. Analysis of follicle cell clones homozygous for a null allele of Ras demonstrates that Ras is required cell-autonomously to repress pipe transcription, the critical first step in embryonic dorsoventral patterning. The effects of aberrant pipe expression in Ras mosaic egg chambers can be ameliorated, however, by post-pipe patterning events, which salvage normal dorsoventral polarity in most embryos derived from egg chambers with dorsal Ras clones. The patterned follicular epithelium also determines the final shape of the eggshell, including the dorsal respiratory appendages, which are formed by the migration of two dorsolateral follicle cell populations. Confocal analyses of mosaic egg chambers demonstrate that Ras is required both cell- and non cell-autonomously for morphogenetic behaviors characteristic of dorsal follicle cell migration, and reveal a novel, Ras-dependent pattern of basal E-cadherin localization in dorsal midline follicle cells. Program in Genetics, Department of Genome Sciences, Box 357730, University of Washington, Seattle, WA 98195-7730, USA. James Karen E KE Dorman Jennie B JB Berg Celeste A CA eng R01-GM-45248 GM NIGMS T32-GM-07735 GM NIGMS Journal Article

England Development 8701744 0 Cadherins 0 Drosophila Proteins EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.8.2 Sulfotransferases EC 2.8.2.- pipe gene product EC 3.6.1.- ras Proteins IM Animal Body Patterning genetics Cadherins metabolism Cell Movement Cell Size Drosophila Proteins genetics physiology Drosophila melanogaster embryology genetics physiology Female Genes, Insect Genes, erbB-1 Genes, ras Models, Biological Mosaicism Mutation Oogenesis genetics Ovarian Follicle cytology embryology Receptor, Epidermal Growth Factor genetics physiology Sulfotransferases genetics physiology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. ras Proteins genetics physiology FBrf0092876 97199437 9395407 1997 05 29 1997 05 29 2003 03 28

0960-9822 7 3 1997 Mar 1 Requirement for EGF receptor signalling in neural recruitment during formation of Drosophila chordotonal sense organ clusters. 166-75 BACKGROUND: Drosophila proneural genes act in the process of selecting neural precursors from undifferentiated ectoderm. The proneural gene atonal is required for the development of precursors of both chordotonal organs (stretch receptors) and photoreceptors. Although these types of sensory element are dissimilar in structure and function, they both occur as organized arrays of neurons. Previous studies have shown that clustering of photoreceptors involves local recruitment, and that signalling by the Drosophila epidermal growth factor receptor (DER) pathway is involved in the recruitment process. We present evidence that a similar mechanism is required for the clustering of embryonic chordotonal organs. RESULTS: We have examined the expression patterns of atonal and genes of the DER pathway in wild-type and mutant backgrounds. Expression of atonal was restricted to a subset of the atonal-requiring chordotonal precursors, which we call founder precursors. The remaining precursors required DER signalling for their selection. Signalling by the founder precursors was initiated by atonal activating, directly or indirectly, rhomboid expression in these cells. Signalling by these founder precursors then provoked a response in the surrounding ectodermal cells, as shown by the activation of expression of the DER target genes pointed and argos. The signal and response then led to recruitment of some of the ectodermal cells to the chordotonal precursor cell fate. DER hyperactivation by misexpression of rhomboid resulted in excessive chordotonal precursor recruitment. CONCLUSIONS: Increased numbers of chordotonal precursors are recruited by homeogenetic induction involving signalling via DER from founder precursors to surrounding ectodermal cells. We suggest that the reason chordotonal organs and photoreceptors share a requirement for the proneural gene atonal is that this gene activates a common pathway leading to neural aggregation. Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Edinburgh EH9 3JR, UK. Lage P P Jan Y N YN Jarman A P AP eng Journal Article

ENGLAND Curr Biol 9107782 0 DNA-Binding Proteins 0 Eye Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Proto-Oncogene Proteins 0 Rho protein, Drosophila 0 ato protein 0 pointed protein 0 rho-2 protein, Drosophila 147954-53-8 gil protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Curr Biol. 1997 Mar 1;7(3):R132-5 9162472 Animal Cell Lineage DNA-Binding Proteins biosynthesis genetics physiology Drosophila melanogaster embryology genetics Ectoderm physiology Embryo, Nonmammalian physiology ultrastructure Embryonic Induction physiology Eye Proteins biosynthesis genetics Gene Expression Regulation, Developmental Membrane Proteins biosynthesis genetics physiology Nerve Tissue Proteins biosynthesis genetics Proprioception physiology Proto-Oncogene Proteins biosynthesis genetics Receptor, Epidermal Growth Factor physiology Sense Organs embryology Signal Transduction physiology Support, Non-U.S. Gov't FBrf0111821 99449586 10518507 1999 12 16 1999 12 16 2000 12 18

0950-1991 126 21 1999 Nov The dorsal-open group gene raw is required for restricted DJNK signaling during closure. 4913-23 During dorsal closure in Drosophila melanogaster, cells of the lateral epidermis migrate over the amnioserosa to encase the embryo. At least three classes of dorsal-open group gene products are necessary for this morphogenetic movement. Class I genes code for structural proteins that effect changes in epidermal cell shape and motility. Class II and III genes code for regulatory components of closure: Class II genes encode Drosophila Jun amino (N)-terminal kinase (DJNK) signaling molecules and Class III genes encode Decapentaplegic-mediated signaling molecules. All characterized dorsal-open group gene products function in the epidermis. Here we report a molecular and genetic characterization of raw, a newly defined member of the Class II dorsal-open group genes. We show that the novel protein encoded by raw is required for restriction of DJNK signaling to leading edge epidermal cells as well as for proper development of the amnioserosa. Taken together, our results demonstrate a role for Raw in restriction of epidermal signaling during closure and suggest that this effect may be mediated via the amnioserosa. Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. anthea. letsou@genetics.utah.edu. Byars C L CL Bates K L KL Letsou A A eng GENBANK AF186024 Journal Article

ENGLAND Development 8701744 0 Cytoskeletal Proteins 0 Insect Proteins 0 cyrano protein 0 dpp protein, Drosophila 0 raw protein EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Alleles Amino Acid Sequence Amnion Animal Cloning, Molecular Cytoskeletal Proteins genetics metabolism Drosophila melanogaster embryology genetics Embryo, Nonmammalian Epidermis embryology metabolism Gene Expression Regulation, Developmental Insect Proteins genetics metabolism Mitogen-Activated Protein Kinases metabolism Molecular Sequence Data Mutation Signal Transduction Support, Non-U.S. Gov't Transcription, Genetic FBrf0135845 21206032 11309192 2001 04 19 2001 07 26

0021-9533 114 Pt 9 2001 May KSR: a MAPK scaffold of the Ras pathway? 1609-12 Kinase Suppressor of Ras (KSR) is an intriguing component of the Ras pathway that was first identified by genetic studies performed in Drosophila melanogaster and Caenorhabditis elegans. In both organisms, inactivating mutations in KSR suppress the phenotypic effects induced by activated Ras. These findings together with the fact that KSR contains many structural features characteristic of a protein kinase led to early speculation that KSR is a kinase functioning upstream of the Ras pathway component Raf-1 or in a parallel Ras-dependent pathway. However, in the six years since its discovery, KSR has been found to lack several key properties of known protein kinases, which has cast doubt on whether KSR is indeed a functional enzyme. A major breakthrough in our understanding of the role of KSR in signal transduction has come from recent findings that KSR interacts with several components of the MAP kinase cascade, including Raf-1, MEK1/2 and ERK1/2. The model now emerging is that KSR acts as a scaffolding protein that coordinates the assembly of a membrane-localized, multiprotein MAP kinase complex, a vital step in Ras-mediated signal transduction. Thus, while Kinase Suppressor of Ras may be its name, phosphorylation may not be its game. Regulation of Cell Growth Laboratory, National Cancer Institute, Frederick Cancer Reseach and Development Center, Frederick, MD 21702, USA. morrisod@nciaxp.ncifcrf.gov Morrison D K DK eng Journal Article Review Review, Tutorial

England J Cell Sci 0052457 EC 2.7.1.- KSR-1 protein kinase EC 2.7.1.37 Protein Kinases EC 3.6.1.- ras Proteins IM Animal Protein Kinases metabolism Signal Transduction ras Proteins metabolism 23 FBrf0091071 97132593 8978045 1997 03 31 1997 03 31 2000 12 18

0016-6731 144 4 1996 Dec Contrasting histories of three gene regions associated with In(3L)Payne of Drosophila melanogaster. 1565-75 In the present report, we studied nucleotide variation in three gene regions of Drosophila melanogaster, spanning > 5 kb and showing different degrees of association with the cosmopolitan inversion In(3L)Payne. The analysis of sequence variation in the regions surrounding the breakpoints and the heat shock 83 (Hsp83) gene locus, located close to the distal breakpoint, revealed the absence of shared polymorphisms and the presence of a number of fixed differences between arrangements, indicating absence of genetic exchange. In contrast, for the esterase-6 gene region, located in the center of the inversion, we observed the presence of shared polymorphisms between arrangements suggesting genetic exchange. In the regions close to the breakpoints, the common St arrangement is 10 times more polymorphic than inverted chromosomes. We propose that the lack of recombination between arrangements in these regions coupled with genetic hitchhiking is the best explanation for the low heterozygosity observed in inverted lines. Using the data for the breakpoints, we estimate that this inversion polymorphism is around 0.36 million yr old. Although it is widely accepted that inversions are examples of balanced polymorphisms, none of the current neutrality tests including our Monte Carlo simulations showed significant departure from neutral expectations. Department of Ecology and Evolution, State University of New York, Stony Brook 11794, USA. Hasson E E Eanes W F WF eng GENBANK U57372 U57373 U57374 U57375 U57376 U57377 U57378 U57379 U57380 U57381 U57382 U57383 U57384 U57385 U57386 U57387 U57459 U57460 U57461 U57462 U57463 U57464 U57465 U57466 U57467 U57468 U57469 U57470 U57471 U57472 Journal Article

UNITED STATES Genetics 0374636 0 Heat-Shock Proteins 0 Protozoan Proteins 0 heat-shock protein 83 EC 3.1.1 Carboxylic Ester Hydrolases EC 3.1.1.1 carboxylesterase IM Animal Carboxylic Ester Hydrolases genetics Drosophila melanogaster genetics Genes, Insect genetics Heat-Shock Proteins genetics Inversion (Genetics) Polymorphism (Genetics) Protozoan Proteins genetics Recombination, Genetic Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0112075 20002440 10529426 1999 12 17 1999 12 17 2002 04 19

0950-1991 126 22 1999 Nov The subcellular localization and activity of Drosophila cubitus interruptus are regulated at multiple levels. 5097-106 Cubitus interruptus (Ci), a Drosophila transcription factor, mediates Hedgehog (Hh) signaling during the patterning of embryonic epidermis and larval imaginal discs. In the absence of Hh signal, Ci is cleaved to generate a truncated nuclear form capable of transcriptional repression. Hh signaling stabilizes and activates the full-length Ci protein leading to strong activation of downstream target genes including patched and decapentaplegic. A number of molecules have been implicated in the regulation of Ci. Mutations in these molecules lead to changes in Ci protein level, the extent of Ci proteolysis and the expression of Ci target genes. This paper examines the regulation of Ci subcellular localization and activity. We first characterize a bipartite nuclear localization signal (NLS) within Ci. We propose that the subcellular distribution of Ci is affected by two opposing forces, the action of the NLS and that of at least two regions targeting Ci to the cytoplasm. Further our data show that loss of PKA or Costal-2 activity does not fully mimic Hh signaling, demonstrating that Ci proteolysis and Ci activation are two distinct events which are regulated through different paths. Finally, we propose that there are three levels of apparent Ci activity, corresponding to three zones along the AP axis with different sets of gene expression and different levels of Hh signaling. Department of Biochemistry, Molecular Biology and Cell Biology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA. Wang Q T QT Holmgren R A RA eng GM057450 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Multienzyme Complexes 0 Nuclear Localization Signal 0 Nuclear Proteins 0 Protein Isoforms 0 costal2 protein 0 cubitus interruptus protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 3.4.22 Cysteine Endopeptidases EC 3.4.99.46 multicatalytic endopeptidase complex EC 3.6.1.- Kinesin IM Amino Acid Sequence Animal Biological Transport Conserved Sequence Cyclic AMP-Dependent Protein Kinases metabolism physiology Cysteine Endopeptidases metabolism DNA-Binding Proteins genetics metabolism Drosophila melanogaster metabolism Genes, Reporter Insect Proteins physiology Kinesin genetics Multienzyme Complexes metabolism Nuclear Localization Signal Nuclear Proteins metabolism Phosphorylation Protein Isoforms metabolism Protein-Serine-Threonine Kinases genetics Signal Transduction Subcellular Fractions Support, U.S. Gov't, P.H.S. FBrf0134563 21142285 11245584 2001 03 14 2001 05 21

0950-1991 128 7 2001 Apr Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the Drosophila retina. 1183-91 The Drosophila EGF receptor is required for differentiation of many cell types during eye development. We have used mosaic analysis with definitive null mutations to analyze the effects of complete absence of EGFR, Ras or Raf proteins during eye development. The Egfr, ras and raf genes are each found to be essential for recruitment of R1-R7 cells. In addition Egfr is autonomously required for MAP kinase activation. EGFR is not essential for R8 cell specification, either alone or redundantly with any other receptor that acts through Ras or Raf, or by activating MAP kinase. As with Egfr, loss of ras or raf perturbs the spacing and arrangement of R8 precursor cells. R8 cell spacing is not affected by loss of argos in posteriorly juxtaposed cells, which rules out a model in which EGFR acts through argos expression to position R8 specification in register between adjacent columns of ommatidia. The R8 spacing role of the EGFR was partially affected by simultaneous deletion of spitz and vein, two ligand genes, but the data suggest that EGFR activation independent of spitz and vein is also involved. The results prove that R8 photoreceptors are specified and positioned by distinct mechanisms from photoreceptors R1-R7. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Yang L L Baker N E NE eng GM47892 GM NIGMS Journal Article

England Development 8701744 0 Eye Proteins 0 MAP Kinase Signaling System 0 Nerve Tissue Proteins 147954-53-8 gil protein EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 3.6.1.- ras Proteins IM Animal Cell Differentiation Drosophila melanogaster Eye Proteins genetics physiology MAP Kinase Signaling System Nerve Tissue Proteins genetics physiology Photoreceptors, Invertebrate cytology Proto-Oncogene Proteins c-raf genetics physiology Receptor, Epidermal Growth Factor genetics physiology Retina cytology Support, U.S. Gov't, P.H.S. ras Proteins genetics physiology FBrf0090562 97108731 8951052 1997 01 23 1997 01 23 2002 11 01

0950-1991 122 11 1996 Nov EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm. 3355-62 The induction of different cell fates along the dorsoventral axis of the Drosophila embryo requires a graded activity of the EGF receptor tyrosine kinase (DER). Here we have identified primary and secondary target genes of DER, which mediate the determination of discrete ventral cell fates. High levels of DER activation in the ventralmost cells trigger expression of the transcription factors encoded by ventral nervous system defective (vnd) and pointed P1 (pntPl). Concomitant with the induction of pntP1, high levels of DER activity lead to inactivation of the Yan protein, a transcriptional repressor of Pointed-target genes. These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan. The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. Gabay L L Scholz H H Golembo M M Klaes A A Shilo B Z BZ Klämbt C C eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Eye Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 anterior open protein, Drosophila 0 pointed protein EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal DNA-Binding Proteins physiology Drosophila melanogaster embryology Ectoderm physiology Eye Proteins physiology Gene Expression Regulation, Developmental In Situ Hybridization Morphogenesis Proto-Oncogene Proteins physiology Receptor Protein-Tyrosine Kinases physiology Receptor, Epidermal Growth Factor physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors physiology Transcription, Genetic FBrf0141551 21585689 11729158 2001 11 30 2002 03 19 2002 11 01

0016-6731 159 3 2001 Nov The Trithorax-mimic allele of Enhancer of zeste renders active domains of target genes accessible to polycomb-group-dependent silencing in Drosophila melanogaster. 1135-50 Two antagonistic groups of genes, the trithorax- and the Polycomb-group, are proposed to maintain the appropriate active or inactive state of homeotic genes set up earlier by transiently expressed segmentation genes. Although some details about the mechanism of maintenance are available, it is still unclear how the initially active or inactive chromatin domains are recognized by either the trithorax-group or the Polycomb-group proteins. We describe an unusual dominant allele of a Polycomb-group gene, Enhancer of zeste, which mimics the phenotype of loss-of-function mutations in trithorax-group genes. This mutation, named E(z)(Trithorax mimic) [E(z)(Trm)], contains a single-amino-acid substitution in the conserved SET domain. The strong dominant trithorax-like phenotypes elicited by this E(z) allele suggest that the mutated arginine-741 plays a critical role in distinguishing between active and inactive chromatin domains of the homeotic gene complexes. We have examined the modification of E(z)(Trm) phenotypes by mutant alleles of PcG and trxG genes and other mutations that alter the phosphorylation of nuclear proteins, covalent modifications of histones, or histone dosage. These data implicate some trxG genes in transcriptional repression as well as activation and provide genetic evidence for involvement of histone modifications in PcG/trxG-dependent transcriptional regulation. Institute of Genetics, Biological Research Center, H-6701 Szeged, Hungary. Bajusz I I Sipos L L Györgypál Z Z Carrington E A EA Jones R S RS Gausz J J Gyurkovics H H eng 1266932 PHS GM46567 GM NIGMS Journal Article

United States Genetics 0374636 0 Butyrates 0 DNA-Binding Proteins 0 E(z) protein, Drosophila 0 Histones 0 Insect Proteins 0 Nuclear Proteins 0 Repressor Proteins 0 trithorax gene product 134549-01-2 Polycomb protein, insect IM Acetylation Alleles Amino Acid Sequence Animal Butyrates pharmacology Chromosome Mapping Chromosomes ultrastructure DNA-Binding Proteins genetics Drosophila melanogaster genetics Gene Silencing Genes, Dominant Heterozygote Histones metabolism Immunohistochemistry Insect Proteins genetics Molecular Sequence Data Mutation Nuclear Proteins genetics Phenotype Protein Binding Protein Structure, Tertiary Repressor Proteins genetics Salivary Glands ultrastructure Sequence Analysis, DNA Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0128601 20286523 10825285 2000 09 01 2000 09 01 2000 12 18

0021-9533 113 ( Pt 12) 2000 Jun Subcellular localization of Bic-D::GFP is linked to an asymmetric oocyte nucleus. 2119-27 Bicaudal-D (Bic-D) is essential for the establishment of oocyte fate and subsequently for polarity formation within the developing Drosophila oocyte. To find out where in the germ cells Bic-D performs its various functions we made transgenic flies expressing a chimeric Bic-D::GFP fusion protein. Once Bic-D::GFP preferentially accumulates in the oocyte, it shows an initial anterior localization in germarial region 2. In the subsequent egg chamber stages 1-6 Bic-D::GFP preferentially accumulates between the oocyte nucleus and the posterior cortex in a focus that is consistently aligned with a crater-like indentation in the oocyte nucleus. After stage 6 Bic-D::GFP fluorescent signal is predominantly found between the oocyte nucleus and the dorso-anterior cortex. During the different phases several genes have been found to be required for the establishment of the new Bic-D::GFP distribution patterns. Dynein heavy chain (Dhc), spindle (spn) genes and maelstrom (mael) are required for the re-localization of the Bic-D::GFP focus from its anterior to its posterior oocyte position. Genes predicted to encode proteins that interact with RNA (egalitarian and orb) are required for the normal subcellular distribution of Bic-D::GFP in the germarium, and another potential RNA binding protein, spn-E, is required for proper transport of Bic-D::GFP from the nurse cells to the oocyte in later oogenesis stages. The results indicate that Bic-D requires the activity of mRNA binding proteins and a negative-end directed microtubule motor to localize to the appropriate cellular domains. Asymmetric subcellular accumulation of Bic-D and the polarization of the oocyte nucleus may reflect the function of this localization machinery in vectorial mRNA localization and in tethering of the oocyte nucleus. The subcellular polarity defined by the Bic-D focus and the nuclear polarity marks some of the first steps in antero-posterior and subsequently in dorso-ventral polarity formation. McGill University, Department of Biology, Montréal, Québec, Canada, H3A 1B1. Paré C C Suter B B eng Journal Article

ENGLAND J Cell Sci 0052457 0 Insect Proteins 0 Luminescent Proteins 0 Recombinant Fusion Proteins 0 sycaudalD protein, Drosophila 147336-22-9 green fluorescent protein IM Animal Cell Nucleus metabolism ultrastructure Drosophila melanogaster Female Insect Proteins genetics metabolism Luminescent Proteins genetics metabolism Oocytes metabolism ultrastructure Recombinant Fusion Proteins genetics metabolism Support, Non-U.S. Gov't FBrf0125408 21079835 11212311 2001 02 09 2001 02 15 2001 11 02

1420-682X 56 7-8 1999 Nov 15 Sexual behavior mutants revisited: molecular and cellular basis of Drosophila mating. 634-46 The study of Drosophila melanogaster by a combination of forward genetics with specific mutants, and reverse genetics, in which a given gene is expressed in an appropriate brain area to test its effect on behavior, provides a unique opportunity to explore the causal relationship between a particular gene, its function in the cell and the behavioral outcome at the organismic level. Enhanced male-to-male courtship has been shown to occur as a result of mutations in several different genes. For example, the Voila mutant exhibits intense GAL4 reporter expression in the tarsal gustatory sensilla, suggesting the importance of tapping by a male on the female abdomen with his forelegs. Feminization of parts of the antennal lobe and mushroom body by targeted expression of a female-determining gene transformer+ (tra+) drives the male to court other males. Mutations in the tra target gene fruitless (fru), which is expressed in the antennal lobe as well as the suboesophageal ganglion (the gustatory inputs are processed here), also induce homosexual courtship in males. These results suggest that sensory inputs mediated and/or processed by the tarsal receptors, suboesophageal ganglion, antennal lobe and mushroom body contribute to the regulation of male-female courtship. Mosaic analysis localized the neural center for male courtship behavior to the posterior dorsal brain, in which the sensory information processed by the aforementioned neural structures may be integrated. Another mosaic study mapped the neural center for female sexual behavior, as measured by her receptiveness to copulation, to the anterior dorsal brain. The issue as to how the mutations that reduce female sexual receptiveness, e.g. dissatisfaction (dsf), spinster (spin) and chaste (cht), affect the structure and/or function of this neural center deserves to be addressed urgently. ERATO Yamamoto Behavior Genes Project, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo, Japan. daichan@mn.waseda.ac.jp Yamamoto D D Nakano Y Y eng Journal Article Review Review, Tutorial

Switzerland Cell Mol Life Sci 9705402 0 Pheromones IM Animal Animals, Genetically Modified Copulation physiology Drosophila melanogaster genetics physiology Female Genes, Insect genetics Male Motor Activity physiology Mutation genetics Pheromones physiology Receptors, Sensory physiology Sex Behavior, Animal physiology 141 FBrf0080012 95178745 7873789 1995 04 06 1995 04 06 2001 11 02

1058-8388 201 2 1994 Oct Differential expression during embryogenesis of three genes clustered in the Ras1 region of Drosophila melanogaster. 179-90 Transcription mapping and nucleotide sequence analysis reveal that the genomic region of the Drosophila Ras1 gene contains a cluster of three closely localized genes. A gene termed Rlb1 is located nearby and upstream of Ras1, and is oriented in the opposite polarity relative to Ras1. In addition, a third gene termed Rlc1, is found at a very close proximity downstream to Rlb1. Ras1, the homologue of the human transforming ras genes, has been shown to be active in the posterior termini of the Drosophila embryo and in the eye imaginal disc in pathways of cell fate determination. We demonstrate that during embryogenesis Ras1 transcripts are restricted mainly to the embryonic central nervous system, suggesting that the gene product also may have a role in these nerve cells. Rlb1 encodes for a novel, lysine-rich basic protein. It is expressed mainly in the developing midgut and in the somatic mesoderm. Rlc1 also encodes for a novel, basic protein. The expression of Rlc1 during embryogenesis is similar, but not identical, to the expression pattern detected for Ras1. The vertebrate p21Ras proteins are bound to the inner face of the cell membrane. Ras1, the Drosophila homologue of p21, and the Rlb1 protein, are also non-cytoplasmic, membranous proteins. Rlb1 is found in the cell membrane of larval midgut epithelial cells. In addition, Rlb1 is detected in the nuclei of these cells, and in the nuclei of the midgut imaginal cells. Department of Biology, Technion-Israel Institute of Technology, Haifa. Ezer S T ST Sahar D D Salzberg A A Lev Z Z eng GENBANK X73216 X73217 X73218 X73219 X73220 Journal Article

UNITED STATES Dev Dyn 9201927 0 DNA, Complementary 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Recombinant Fusion Proteins 0 Rlb1 protein 0 Rlc1 protein EC 3.6.1.- Proto-Oncogene Protein p21(ras) IM CDC25 Gap1 Ki-rev R-ras RAS Raf1 Rap1 Ras1 Ras2 Ras3 Rlb1 Rlc1 SCD25 Sos boss ras Amino Acid Sequence Animal Animals, Genetically Modified Base Sequence Cloning, Molecular DNA, Complementary genetics Digestive System embryology Drosophila melanogaster embryology genetics Embryo, Nonmammalian metabolism ultrastructure Gene Expression Regulation, Developmental Genes, Structural, Insect In Situ Hybridization Membrane Proteins biosynthesis genetics Molecular Sequence Data Molecular Weight Multigene Family Nerve Tissue Proteins biosynthesis genetics Proto-Oncogene Protein p21(ras) biosynthesis genetics Recombinant Fusion Proteins biosynthesis Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription, Genetic FBrf0160454 22698650 12814944 2003 06 19 2003 07 22

0077-8923 995 2003 May Cell migration and programmed cell death of Drosophila germ cells. 117-26 Cell migration and programmed cell death are essential components of animal development and homeostasis, and the germ cells of Drosophila provide a simple genetic system to study the molecular mechanisms that govern these important cellular processes. Detailed descriptions of germ cell migration in Drosophila were accomplished long ago, but most genetic and molecular analyses of the process have occurred within the past 10 years. A few of the genes required for germ cell migration have been identified, and a very interesting picture is emerging. However, a process as complex as cell migration must involve the functions of many more molecules. In addition, cell migration and cell death mechanisms are often linked, as it is important to eliminate cells that are misplaced and could present a danger to the organism. In Drosophila, genes involved in germ cell migration can also affect programmed cell death. Currently, very little is known about how germ cells ectopic to the gonads are eliminated. To date, only four genes have been reported with roles in germ cell death, and three of these have additional functions in germ cell pathfinding. The nature of the cell death program has not been elucidated. Here, I provide a brief review of Drosophila germ cell migration and programmed cell death at both the descriptive and molecular levels. Many questions remain to be answered, but advances made in recent years are providing useful insights into these critical biological phenomena. Department of Zoology and Genetics, Iowa State University, Ames, Iowa 50011, USA. ccoffman@isastate.edu Coffman Clark R CR eng Journal Article Review Review, Tutorial

United States Ann N Y Acad Sci 7506858 0 Drosophila Proteins IM Animal Apoptosis Cell Movement Drosophila Proteins physiology Drosophila melanogaster cytology embryology Female Germ Cells cytology physiology Signal Transduction 67 FBrf0079921 95203734 7896146 1995 04 21 1995 04 21 2000 12 18

0016-6707 94 2-3 1994 Genetic, molecular and developmental analysis of the glutamine synthetase isozymes of Drosophila melanogaster. 275-81 The glutamine synthetase isozymes of Drosophila melanogaster offer an attractive model for the study of the molecular genetics and evolution of a small gene family encoding enzymatic isoforms that evolved to assume a variety of specific and sometimes essential biological functions. In Drosophila melanogaster two GS isozymes have been described which exhibit different cellular localisation and are coded by a two-member gene family. The mitochondrial GS structural gene resides at the 21B region of the second chromosome, the structural gene for the cytosolic isoform at the 10B region of the X chromosome. cDNA clones corresponding to the two genes have been isolated and sequenced. Evolutionary analysis data are in accord with the hypothesis that the two Drosophila glutamine synthetase genes are derived from a duplication event that occurred near the time of divergence between Insecta and Vertebrata. Both isoforms catalyse all reactions catalysed by other glutamine synthetases, but the different kinetic parameters and the different cellular compartmentalisation suggest strong functional specialisation. In fact, mutations of the mitochondrial GS gene produce embryo-lethal female sterility, defining a function of the gene product essential for the early stages of embryonic development. Preliminary results show strikingly distinct spatial and temporal patterns of expression of the two isoforms at later stages of development. Istituto di Genetica dell'Università di Bari, Italy. Caggese C C Barsanti P P Viggiano L L Bozzetti M P MP Caizzi R R eng Journal Article Review Review, Tutorial

NETHERLANDS Genetica 0370740 0 Isoenzymes EC 6.3.1.2 Glutamate-Ammonia Ligase IM Animal Drosophila melanogaster enzymology genetics Female Genes, Structural, Insect Glutamate-Ammonia Ligase Isoenzymes Phylogeny Support, Non-U.S. Gov't 32 FBrf0141471 21642114 11782316 2002 01 09 2002 02 08 2003 07 09

1534-5807 2 1 2002 Jan Drosophila nicastrin is essential for the intramembranous cleavage of notch. 79-89 The catalytic subunit of gamma-secretase is thought to be Presenilin, which is required for both the cleavage of APP and in the processing of Notch. Presenilin is found in a multisubunit complex that also contains Nicastrin. Nicastrin has been implicated in APP processing, but its role in Notch signaling remains unclear. Here we show that Drosophila Nicastrin is required for Notch signaling, and acts specifically at the S3 cleavage step. Partially processed Notch accumulates apically in nicastrin and presenilin mutant follicle cells. nicastrin and presenilin mutations also disrupt the spectrin cytoskeleton, suggesting that the gamma-secretase complex has another function in Drosophila in addition to its role in processing Notch and APP. Wellcome/CRC Institute and Department of Genetics, University of Cambridge, Tennis Court Road, CB2 1QR, Cambridge, United Kingdom. López-Schier Hernán H St Johnston Daniel D eng Journal Article

United States Dev Cell 101120028 0 FyuA protein, Yersinia 0 Membrane Glycoproteins 0 Membrane Proteins 0 Receptors, Cell Surface 0 nicastrin protein 0 notch protein 12634-43-4 Spectrin IM Amino Acid Sequence Animal Cytoskeleton metabolism Drosophila melanogaster genetics Intracellular Membranes metabolism Membrane Glycoproteins genetics metabolism Membrane Proteins metabolism Molecular Sequence Data Mutation physiology Receptors, Cell Surface genetics metabolism Signal Transduction physiology Spectrin metabolism Support, Non-U.S. Gov't FBrf0098317 97417584 9272957 1997 09 10 1997 09 10 2002 11 01

0950-1991 124 16 1997 Aug Mothers against dpp participates in a DDP/TGF-beta responsive serine-threonine kinase signal transduction cascade. 3167-76 Mothers against dpp (Mad) is the prototype of a family of genes required for signaling by TGF-beta related ligands. In Drosophila, Mad is specifically required in cells responding to Decapentaplegic (DPP) signals. We further specify the role of Mad in DPP-mediated signaling by utilizing tkvQ199D, an activated form of the DPP type I receptor serine-threonine kinase thick veins (tkv). In the embryonic midgut, tkvQ199D mimics DPP-mediated inductive interactions. Homozygous Mad mutations block signaling by tkvQ199D. Appropriate responses to signaling by tkvQ199D are restored by expression of MAD protein in DPP-target cells. Endogenous MAD is phosphorylated in a ligand-dependent manner in Drosophila cell culture. DPP overexpression in the embryonic midgut induces MAD nuclear accumulation; after withdrawal of the overexpressed DPP signal, MAD is detected only in the cytoplasm. However, in three different tissues and developmental stages actively responding to endogenous DPP, MAD protein is detected in the cytoplasm but not in the nucleus. From these observations, we discuss possible roles for MAD in a DPP-dependent serine-threonine kinase signal transduction cascade integral to the proper interpretation of DPP signals. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Newfeld S J SJ Mehra A A Singer M A MA Wrana J L JL Attisano L L Gelbart W M WM eng Journal Article

ENGLAND Development 8701744 0 Bone Morphogenetic Proteins 0 DNA-Binding Proteins 0 Insect Proteins 0 Ligands 0 Mad protein 0 Receptors, Cell Surface 0 Recombinant Fusion Proteins 0 Transforming Growth Factor beta 0 bone morphogenetic protein 2 0 dpp protein, Drosophila EC 2.7.1.- DTFR protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Bone Morphogenetic Proteins pharmacology Cell Nucleus chemistry Cytoplasm chemistry DNA-Binding Proteins analysis genetics metabolism Digestive System chemistry embryology Drosophila melanogaster embryology Endoderm Insect Proteins genetics physiology Ligands Mesoderm Phosphorylation Protein-Serine-Threonine Kinases metabolism Receptors, Cell Surface metabolism Recombinant Fusion Proteins Signal Transduction physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transforming Growth Factor beta genetics FBrf0151939 22291607 12403717 2002 10 29 2003 01 21 2003 06 16

0950-1991 129 23 2002 Dec Kinesin light chain-independent function of the Kinesin heavy chain in cytoplasmic streaming and posterior localisation in the Drosophila oocyte. 5473-85 Microtubules and the Kinesin heavy chain, the force-generating component of the plus end-directed microtubule motor Kinesin I are required for the localisation of oskar mRNA to the posterior pole of the Drosophila oocyte, an essential step in the determination of the anteroposterior axis. We show that the Kinesin heavy chain is also required for the posterior localisation of Dynein, and for all cytoplasmic movements within the oocyte. Furthermore, the KHC localises transiently to the posterior pole in an oskar mRNA-independent manner. Surprisingly, cytoplasmic streaming still occurs in kinesin light chain null mutants, and both oskar mRNA and Dynein localise to the posterior pole. Thus, the Kinesin heavy chain can function independently of the light chain in the oocyte, indicating that it associates with its cargoes by a novel mechanism. Wellcome Trust/Cancer Research UK Institute and Department of Genetics, University of Cambridge, Tennis Court Road, UK. Palacios Isabel M IM St Johnston Daniel D eng Journal Article

England Development 8701744 0 Carrier Proteins 0 Drosophila Proteins 0 Membrane Proteins 0 Microtubule-Associated Proteins 0 RNA-Binding Proteins 0 Recombinant Fusion Proteins 0 Sunday Driver protein 0 kinesin light-chain protein 0 oskar protein, Drosophila 139568-71-1 staufen protein, Drosophila EC 3.6.1.- Kinesin EC 3.6.1.33 Dynein ATPase IM Animal Biological Transport physiology Carrier Proteins metabolism Cell Polarity Cytoplasmic Streaming physiology Drosophila Proteins genetics metabolism Drosophila melanogaster genetics physiology Dynein ATPase metabolism In Situ Hybridization Kinesin genetics metabolism Membrane Proteins metabolism Microtubule-Associated Proteins genetics metabolism Microtubules metabolism Oocytes cytology physiology Oogenesis physiology RNA-Binding Proteins genetics metabolism Recombinant Fusion Proteins metabolism Support, Non-U.S. Gov't FBrf0089747 97001128 8844158 1997 01 23 1997 01 23 2000 12 18

0016-6731 143 4 1996 Aug Length variation of CAG/CAA trinucleotide repeats in natural populations of Drosophila melanogaster and its relation to the recombination rate. 1713-25 Eleven genes distributed along the Drosophila melanogaster chromosome 2 and showing exonic tandem repeats of glutamine codons (CAG or CAA) were surveyed for length variation in a sample of four European and African populations. Only one gene was monomorphic. Eight genes were polymorphic in all populations, with a total number of alleles varying between five and 12 for 120 chromosomes. The average heterozygozity per locus and population was 0.41. Selective neutrality in length variation could not be rejected under the assumptions of the infinite allele model. Significant population subdivision was found though no geographical pattern emerged, all populations being equally different. Significant linkage disequilibrium was found in four out of seven cases where the genetic distance between loci was < 1 cM and was negligible when the distance was larger. There is evidence that these associations were established after the populations separated. An unexpected result was that variation at each locus was independent of the coefficient of exchange, although the latter ranged from zero to the relatively high value of 6.7%. This would indicate that background selection and selective hitchhiking, which are thought to affect levels of nucleotide substitution polymorphism, have no effect on trinucleotide repeat variation. Laboratoire d'Ecologie, Université Pierre-et-Marie Curie, Paris, France. Michalakis Y Y Veuille M M eng Journal Article

UNITED STATES Genetics 0374636 0 DNA Primers IM Alleles Animal Base Sequence Comparative Study DNA Primers genetics Drosophila melanogaster genetics Female Genes, Insect Genetics, Population Linkage Disequilibrium Male Minisatellite Repeats Models, Genetic Molecular Sequence Data Polymorphism (Genetics) Recombination, Genetic Selection (Genetics) Support, Non-U.S. Gov't Trinucleotide Repeats Variation (Genetics) FBrf0160683 22640876 12756184 2003 05 20 2003 09 10

0950-1991 130 13 2003 Jul Gata factor Pannier is required to establish competence for heart progenitor formation. 3027-38 Inductive signaling is of pivotal importance for developmental patterns to form. In Drosophila, the transfer of TGFbeta (Dpp) and Wnt (Wg) signaling information from the ectoderm to the underlying mesoderm induces cardiac-specific differentiation in the presence of Tinman, a mesoderm-specific homeobox transcription factor. We present evidence that the Gata transcription factor, Pannier, and its binding partner U-shaped, also a zinc-finger protein, cooperate in the process of heart development. Loss-of-function and germ layer-specific rescue experiments suggest that pannier provides an essential function in the mesoderm for initiation of cardiac-specific expression of tinman and for specification of the heart primordium. u-shaped also promotes heart development, but unlike pannier, only by maintaining tinman expression in the cardiogenic region. By contrast, pan-mesodermal overexpression of pannier ectopically expands tinman expression, whereas overexpression of u-shaped inhibits cardiogenesis. Both factors are also required for maintaining dpp expression after germ band retraction in the dorsal ectoderm. Thus, we propose that Pannier mediates as well as maintains the cardiogenic Dpp signal. In support, we find that manipulation of pannier activity in either germ layer affects cardiac specification, suggesting that its function is required in both the mesoderm and the ectoderm. Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Klinedinst Susan L SL Bodmer Rolf R eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Repressor Proteins 0 Trans-Activators 0 Transcription Factors 0 dpp protein, Drosophila 0 pannier protein 0 tinman protein 0 u-shaped protein IM Animal Drosophila Proteins genetics metabolism Drosophila melanogaster embryology growth & development physiology Ectoderm cytology physiology Embryonic Induction Gene Expression Regulation, Developmental Heart embryology In Situ Hybridization Mesoderm cytology physiology Morphogenesis Organisms, Genetically Modified Phenotype Repressor Proteins genetics metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism Transcription Factors genetics metabolism FBrf0108684 99282498 10353900 1999 07 08 1999 07 08 2003 09 17

0016-6731 152 2 1999 Jun The Drosophila melanogaster Suppressor of deltex gene, a regulator of the Notch receptor signaling pathway, is an E3 class ubiquitin ligase. 567-76 During development, the Notch receptor regulates many cell fate decisions by a signaling pathway that has been conserved during evolution. One positive regulator of Notch is Deltex, a cytoplasmic, zinc finger domain protein, which binds to the intracellular domain of Notch. Phenotypes resulting from mutations in deltex resemble loss-of-function Notch phenotypes and are suppressed by the mutation Suppressor of deltex [Su(dx)]. Homozygous Su(dx) mutations result in wing-vein phenotypes and interact genetically with Notch pathway genes. We have previously defined Su(dx) genetically as a negative regulator of Notch signaling. Here we present the molecular identification of the Su(dx) gene product. Su(dx) belongs to a family of E3 ubiquitin ligase proteins containing membrane-targeting C2 domains and WW domains that mediate protein-protein interactions through recognition of proline-rich peptide sequences. We have identified a seven-codon deletion in a Su(dx) mutant allele and we show that expression of Su(dx) cDNA rescues Su(dx) mutant phenotypes. Overexpression of Su(dx) also results in ectopic vein differentiation, wing margin loss, and wing growth phenotypes and enhances the phenotypes of loss-of-function mutations in Notch, evidence that supports the conclusion that Su(dx) has a role in the downregulation of Notch signaling. University of Manchester, School of Biological Sciences, Manchester M13 9PT, United Kingdom. Cornell M M Evans D A DA Mann R R Fostier M M Flasza M M Monthatong M M Artavanis-Tsakonas S S Baron M M eng GENBANK AF152865 Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Membrane Proteins 0 Receptors, Cell Surface 0 deltex protein, Drosophila 0 notch protein EC 6. Ligases EC 6.3.2.- Suppressor of deltex protein, Drosophila EC 6.3.2.19 ubiquitin-protein ligase IM Amino Acid Sequence Animal Cloning, Molecular Drosophila melanogaster chemistry enzymology genetics Evolution, Molecular Gene Expression Regulation, Developmental Genes, Structural, Insect genetics Genes, Suppressor genetics Genetic Complementation Test Insect Proteins genetics Ligases genetics Membrane Proteins physiology Molecular Sequence Data Mutation Phenotype Phylogeny Receptors, Cell Surface physiology Sequence Alignment Sequence Analysis, DNA Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Transfection Wing embryology growth & development metabolism FBrf0045261 86259667 3014506 1986 08 01 1986 08 01 2000 12 18

0027-8424 83 13 1986 Jul Isolation of a Drosophila genomic sequence homologous to the kinase domain of the human insulin receptor and detection of the phosphorylated Drosophila receptor with an anti-peptide antibody. 4710-4 A Drosophila genomic fragment has been isolated with a deduced amino acid sequence that is strikingly homologous to that of the kinase domain of the human insulin receptor. The Drosophila DNA hybridizes with an 11-kilobase mRNA that is most prominent in 8- to 12-hr embryos. An anti-peptide antibody prepared to a sequence in the human insulin receptor kinase domain that is conserved in the Drosophila sequence immunoprecipitates a single 95-kDa Drosophila protein whose phosphorylation on tyrosine residues is dependent on insulin. We conclude that the DNA sequence is that of the kinase domain of the Drosophila insulin receptor and that the 95-kDa phosphoprotein is the autophosphorylated beta subunit of that receptor. The results are compatible with our previous reports demonstrating a specific insulin-binding Drosophila glycoprotein and an insulin-dependent tyrosine protein kinase whose activity is greatest during embryogenesis. The observations suggest a role for insulin-dependent protein tyrosine phosphorylation during embryogenesis. Petruzzelli L L Herrera R R Arenas-Garcia R R Fernandez R R Birnbaum M J MJ Rosen O M OM eng GENBANK M13568 2R01 AM31358 AM NIADDK 2R01 GM21258 GM NIGMS 5R01 GM34555 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Phosphoproteins 0 RNA, Messenger EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Insulin EC 3.1.21 DNA Restriction Enzymes IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Molecular Comparative Study DNA Restriction Enzymes diagnostic use Drosophila melanogaster genetics Human Molecular Weight Phosphoproteins genetics Protein-Tyrosine Kinase genetics immunology RNA, Messenger genetics Receptor, Insulin genetics immunology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0058498 93185922 8166882 1993 04 05 1993 04 05 2000 12 18

0378-1119 124 2 1993 Feb 28 Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell-cell communication. 183-9 The complete nucleotide sequence of the coding region of hedgehog (hh), a segment-polarity gene in Drosophila melanogaster, was determined. The gene was found to include three exons which would encode a 421- (or 471-) amino acid (aa) polypeptide with a long hydrophobic stretch. The hh mRNA was about 2.3 kb long and expressed throughout development. The hh expression in an embryo occurred in stripes, while that in imaginal discs occurred in the posterior compartment. As a whole, the spatial expression pattern of hh mRNA was very similar to that of engrailed (en), a homeobox gene required for the formation of the anterior-posterior compartment boundary. Unlike en, no hh expression was observed in the central nervous system. Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan. Tashiro S S Michiue T T Higashijima S S Zenno S S Ishimaru S S Takahashi F F Orihara M M Kojima T T Saigo K K eng GENBANK L03650 L03651 L03652 L03653 L03654 L05404 L05405 X69146 X69147 X69148 Journal Article

NETHERLANDS Gene 7706761 0 Membrane Proteins 0 Proteins 149291-21-4 hedgehog protein, Drosophila 9007-49-2 DNA IM Animal Base Sequence Blotting, Northern Cell Communication genetics physiology Cloning, Molecular DNA Drosophila melanogaster embryology genetics Membrane Proteins genetics physiology Molecular Sequence Data Proteins genetics physiology Support, Non-U.S. Gov't FBrf0106872 99148137 10022978 1999 06 14 1999 06 14 2000 12 18

1088-9051 9 2 1999 Feb Analysis of two cosmid clones from chromosome 4 of Drosophila melanogaster reveals two new genes amid an unusual arrangement of repeated sequences. 137-49 Chromosome 4 from Drosophila melanogaster has several unusual features that distinguish it from the other chromosomes. These include a diffuse appearance in salivary gland polytene chromosomes, an absence of recombination, and the variegated expression of P-element transgenes. As part of a larger project to understand these properties, we are assembling a physical map of this chromosome. Here we report the sequence of two cosmids representing approximately 5% of the polytenized region. Both cosmid clones contain numerous repeated DNA sequences, as identified by cross hybridization with labeled genomic DNA, BLAST searches, and dot matrix analysis, which are positioned between and within the transcribed sequences. The repetitive sequences include three copies of the mobile element Hoppel, one copy of the mobile element HB, and 18 DINE repeats. DINE is a novel, short repeated sequence dispersed throughout both cosmid sequences. One cosmid includes the previously described cubitus interruptus (ci) gene and two new genes: that a gene with a predicted amino acid sequence similar to ribosomal protein S3a which is consistent with the Minute(4)101 locus thought to be in the region, and a novel member of the protein family that includes plexin and met-hepatocyte growth factor receptor. The other cosmid contains only the two short 5'-most exons from the zinc-finger-homolog-2 (zfh-2) gene. This is the first extensive sequence analysis of noncoding DNA from chromosome 4. The distribution of the various repeats suggests its organization is similar to the beta-heterochromatic regions near the base of the major chromosome arms. Such a pattern may account for the diffuse banding of the polytene chromosome 4 and the variegation of many P-element transgenes on the chromosome. Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9, Canada. john.locke@ualberta.ca Locke J J Podemski L L Roy K K Pilgrim D D Hodgetts R R eng Journal Article

UNITED STATES Genome Res 9518021 0 Cosmids IM Amino Acid Sequence Animal Base Sequence Chromosomes genetics Cosmids genetics Drosophila melanogaster genetics Genes, Insect genetics Mice Molecular Sequence Data Multigene Family Repetitive Sequences, Nucleic Acid genetics Sequence Alignment Sequence Analysis, DNA Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't FBrf0078802 95113163 7813765 1995 02 09 1995 02 09 2002 11 01

0012-1606 166 2 1994 Dec Signaling by wingless in Drosophila. 396-414 Wingless, a member of the Wnt gene family, is an essential gene for segmentation in Drosophila, and is also involved in many other patterning events. The gene encodes a secreted protein that can regulate gene expression in adjacent cells. Recently, significant progress has been made in elucidating the signal transduction pathway of wingless, mainly by genetic experiments but increasingly also at the biochemical level. While many components of wingless signaling, in particular a receptor, remain to be identified, our current understanding of wingless pathway is more advanced than that of other Wnt genes. We will give an overview of the various roles of wingless in development, and we will then summarize the wingless signaling pathway as it has emerged from genetic and biochemical studies. Where appropriate, wingless signaling will be compared to the activity of vertebrate Wnt proteins. Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, California 94305. Klingensmith J J Nusse R R eng Journal Article Review Review, Academic

UNITED STATES Dev Biol 0372762 0 Cytoskeletal Proteins 0 Dsh protein 0 Proteins 0 Proto-Oncogene Proteins 0 armadillo protein, Drosophila 117758-26-6 wingless protein, Drosophila 138930-21-9 CAP102 IM Notch Wnt-1 arm dsh porc wg Animal Cell Division Cytoskeletal Proteins physiology Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Structural, Insect Morphogenesis Proteins physiology Proto-Oncogene Proteins physiology Signal Transduction Support, Non-U.S. Gov't 126 FBrf0110930 99375333 10444379 1999 12 29 1999 12 29 2000 12 18

0021-9533 112 ( Pt 17) 1999 Sep Dynamic rearrangement of the spectrin membrane skeleton during the generation of epithelial polarity in Drosophila. 2843-52 The origin of epithelial cell polarity during development is a fundamental problem in cell biology. Central to this process is the establishment of asymmetric membrane domains that will ultimately form the apical and basolateral surfaces. The spectrin-based membrane skeleton has long been thought to participate in the generation of this asymmetry. Drosophila melanogaster contains two known (beta)-spectrin isoforms: a conventional (beta)-spectrin chain, and the novel isoform (beta)(Heavy)-spectrin. These two proteins are restricted to the basolateral and apical membrane domains, respectively. To assay for the emergence of membrane asymmetry, we have characterized the distribution of these two (beta)-spectrins during the formation of the primary epithelium in the fly embryo. Our results show that the syncytial embryo contains a maternally established apical membrane skeleton containing (beta)(Heavy)-spectrin into which the basolateral (beta)-spectrin membrane skeleton is added. We have called this process basolateral interpolation. Although basolateral membrane skeleton addition begins during cellularization, it does not become fully established until the formation of a mature zonula adherens at mid to late gastrulation. The behavior of (beta)-spectrin is consistent with a primary role in establishing and/or maintaining the basolateral domain while the behavior of (beta)(Heavy)-spectrin suggests that its primary role is associated with a specialized DE-cadherin complex associated with the furrow canals and with the maturation of the zonula adherens. Thus, the apical spectrin membrane skeleton appears to play a distinct rather than analogous role to the basolateral spectrin membrane skeleton, during the emergence of cell polarity. We find that there are several parallels between our observations and previous studies on the establishment of primary epithelial polarity in vertebrates, suggesting that basolateral interpolation of the membrane skeleton may be a common mechanism in many organisms. Department of Biology and Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. GXT5@PSU.EDU Thomas G H GH Williams J A JA eng GM52506 GM NIGMS Journal Article

ENGLAND J Cell Sci 0052457 0 Cadherins 0 Cytoskeletal Proteins 0 Insect Proteins 0 Protein Isoforms 12634-43-4 Spectrin IM Animal Blastoderm cytology Cadherins metabolism Cell Polarity Cytoskeletal Proteins metabolism Cytoskeleton ultrastructure Drosophila melanogaster cytology embryology Epithelial Cells metabolism ultrastructure Insect Proteins metabolism Morphogenesis Protein Isoforms metabolism Spectrin metabolism Support, U.S. Gov't, P.H.S. FBrf0091142 97132603 8978055 1997 03 31 1997 03 31 2000 12 18

0016-6731 144 4 1996 Dec Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations. 1681-92 Screens for zygotic lethal mutations that are associated with specific maternal effect lethal phenotypes have only been conducted for the X chromosome. To identify loci on the autosomes, which represent four-fifths of the Drosophila genome, we have used the autosomal "FLP-DFS" technique to screen a collection of 496 P element-induced mutations established by the Berkeley Drosophila Genome Project. We have identified 64 new loci whose gene products are required for proper egg formation or normal embryonic development. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. perrimon@rascal.med.harvard.edu Perrimon N N Lanjuin A A Arnold C C Noll E E eng Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements IM Animal Chromosome Mapping DNA Transposable Elements genetics Drosophila melanogaster genetics Genetic Techniques Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0064394 94063486 8244010 1994 01 06 1994 01 06 2000 12 18

0016-6731 135 2 1993 Oct Toward a molecular genetic analysis of spermatogenesis in Drosophila melanogaster: characterization of male-sterile mutants generated by single P element mutagenesis. 489-505 We describe 83 recessive autosomal male-sterile mutations, generated by single P element mutagenesis in Drosophila melanogaster. Each mutation has been localized to a lettered subdivision of the polytene map. Reversion analyses, as well as complementation tests using available chromosomal deficiencies, indicate that the insertions are responsible for the mutant phenotypes. These mutations represent 63 complementation groups, 58 of which are required for spermatogenesis. Phenotypes of the spermatogenesis mutants were analyzed by light microscopy. Mutations in 12 loci affect germline proliferation, spermatocyte growth, or meiosis. Mutations in 46 other loci disrupt differentiation and maturation of spermatids into motile sperm. This collection of male-sterile mutants provides the basis for a molecular genetic analysis of spermatogenesis. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9038. Castrillon D H DH Gönczy P P Alexander S S Rawson R R Eberhart C G CG Viswanathan S S DiNardo S S Wasserman S A SA eng GM-08014 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Genetic Markers IM Animal Cell Differentiation Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics physiology Female Fertility Genes, Recessive Genetic Complementation Test Genetic Markers In Situ Hybridization Infertility, Male genetics Male Meiosis genetics Mutagenesis, Insertional Phenotype Salivary Glands cytology Spermatogenesis genetics Spermatozoa cytology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0100569 98152314 9491614 1998 04 14 1998 04 14 2000 12 18

0737-4038 15 2 1998 Feb Conservation of locus-specific microsatellite variability across species: a comparison of two Drosophila sibling species, D. melanogaster and D. simulans. 176-84 Fifteen microsatellite loci were studied in Drosophila melanogaster and Drosophila simulans, two closely related sibling species which split 2-3.5 MYA. Within-species variances in repeat number were found to differ up to 1,000-fold among individual microsatellite loci. A significant correlation of log variances between both species indicated a locus-specific mutation rate of microsatellites. Hence, locus-specific effects are apparently among the major forces influencing microsatellite variation and deserve more consideration in microsatellite analysis. Institut für Tierzucht und Genetik, Veterinärmedizinische Universität Wien, Austria. Harr B B Zangerl B B Brem G G Schlötterer C C eng Journal Article

UNITED STATES Mol Biol Evol 8501455 0 Genetic Markers IM Africa Animal Comparative Study Drosophila classification genetics Drosophila melanogaster classification genetics Evolution, Molecular Genetic Markers Microsatellite Repeats Phylogeny Polymerase Chain Reaction Species Specificity Support, Non-U.S. Gov't FBrf0158857 22523833 12636913 2003 03 14 2003 04 18 2003 06 16

1534-5807 4 3 2003 Mar Drosophila gurken (TGFalpha) mRNA localizes as particles that move within the oocyte in two dynein-dependent steps. 307-19 In Drosophila oocytes, gurken mRNA localization orientates the TGF-alpha signal to establish the anteroposterior and dorsoventral axes. We have elucidated the path and mechanism of gurken mRNA localization by time-lapse cinematography of injected fluorescent transcripts in living oocytes. gurken RNA assembles into particles that move in two distinct steps, both requiring microtubules and cytoplasmic Dynein. gurken particles first move toward the anterior and then turn and move dorsally toward the oocyte nucleus. We present evidence suggesting that the two steps of gurken RNA transport occur on distinct arrays of microtubules. Such distinct microtubule networks could provide a general mechanism for one motor to transport different cargos to distinct subcellular destinations. Wellcome Trust Centre for Cell Biology, ICMB, King's Buildings, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, Scotland, United Kingdom. MacDougall Nina N Clark Alejandra A MacDougall Eilidh E Davis Ilan I eng Journal Article

United States Dev Cell 101120028 0 Fluorescent Dyes 0 Insect Proteins 0 Molecular Motors 0 RNA, Messenger 0 gurken protein, Drosophila 76057-06-2 Transforming Growth Factors EC 3.6.1.33 Dynein ATPase IM Animal Cell Compartmentation physiology Cell Nucleus metabolism ultrastructure Cell Polarity physiology Drosophila melanogaster cytology metabolism Dynein ATPase metabolism Female Fluorescent Antibody Technique Fluorescent Dyes diagnostic use Genes, Reporter genetics Insect Proteins genetics Microtubules metabolism Molecular Motors genetics Oocytes cytology metabolism Protein Transport physiology RNA, Messenger metabolism pharmacology Support, Non-U.S. Gov't Transforming Growth Factors genetics FBrf0080371 95154564 7851643 1995 03 16 1995 03 16 2000 12 18

0012-1606 167 1 1995 Jan The ovarian tumor protein isoforms of Drosophila melanogaster exhibit differences in function, expression, and localization. 201-12 The Drosophila melanogaster ovarian tumor (otu) gene, required for normal proliferation and differentiation of the female germ-line, encodes two cytoplasmic protein isoforms, 98 and 104 kDa. Mutants with defects in this gene are typically grouped into one of three phenotypic classes: quiescent (germ cells do not proliferate), oncogenic or tumorous (germ-line cells proliferate uncontrollably), and differentiated (germ-line cells initiate but do not complete differentiation). Analysis of transformants expressing only one of the otu isoforms showed that the 104-kDa isoform (otu-104) can rescue all classes of otu mutants, whereas only differentiated mutants are rescued to a significant extent by the 98-kDa isoform (otu-98). Western analysis of protein extracts prepared from ovaries of various developmental stages indicated that otu-104 predominates in predifferentiated stages, while otu-98 is prevalent in differentiated egg chambers. Immunolocalization experiments demonstrated that otu protein is present in the cytoplasm of oogonial stem cells that populate third instar larvae and in all germ-line-derived cells until late in oogenesis. In stage 10 egg chambers, otu protein shifts to the subcortical region of nurse cells. This type of analysis also showed that upon formation of a 16-cell syncytium otu-104, but not otu-98, preferentially accumulates in the developing oocyte cytoplasm. The otu mutant protein does not show this pattern of enhanced accumulation, nor does it occur in ovaries of egalitarian and Bicaudal-D mutants, which are defective in oocyte determination. Thus, these studies indicate that the 104-kDa isoform is required for normal proliferation of female germline cells and perhaps for oocyte differentiation. The 98-kDa isoform appears to be dispensable but can provide an otu function needed for the completion of oocyte maturation. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599-3280. Sass G L GL Comer A R AR Searles L L LL eng Journal Article

UNITED STATES Dev Biol 0372762 0 Insect Hormones 0 ovarian tumor protein, Drosophila IM Animal Drosophila melanogaster chemistry Female Immunohistochemistry Insect Hormones analysis genetics physiology Mutation Oogenesis Ovary chemistry Support, U.S. Gov't, Non-P.H.S. FBrf0160839 22640878 12756186 2003 05 20 2003 09 10

0950-1991 130 13 2003 Jul Mechanism of hedgehog signaling during Drosophila eye development. 3053-62 Although Hedgehog (Hh) signaling is essential for morphogenesis of the Drosophila eye, its exact link to the network of tissue-specific genes that regulate retinal determination has remained elusive. In this report, we demonstrate that the retinal determination gene eyes absent (eya) is the crucial link between the Hedgehog signaling pathway and photoreceptor differentiation. Specifically, we show that the mechanism by which Hh signaling controls initiation of photoreceptor differentiation is to alleviate repression of eya and decapentaplegic (dpp) expression by the zinc-finger transcription factor Cubitus interruptus (Ci(rep)). Furthermore, our results suggest that stabilized, full length Ci (Ci(act)) plays little or no role in Drosophila eye development. Moreover, while the effects of Hh are primarily concentration dependent in other tissues, hh signaling in the eye acts as a binary switch to initiate retinal morphogenesis by inducing expression of the tissue-specific factor Eya. Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Pappu Kartik S KS Chen Rui R Middlebrooks Brooke W BW Woo Catherine C Heberlein Ulrike U Mardon Graeme G eng EY02520 EY NEI R01 EY11232-01 EY NEI Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Eye Proteins 0 cubitus interruptus protein 0 dpp protein, Drosophila 0 eyes absent protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Cell Differentiation physiology DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster anatomy & histology embryology growth & development physiology Eye Proteins genetics metabolism Models, Biological Morphogenesis physiology Organisms, Genetically Modified Photoreceptors, Invertebrate cytology embryology growth & development physiology Signal Transduction physiology Support, U.S. Gov't, P.H.S. Wing anatomy & histology embryology growth & development FBrf0107732 99160565 10049924 1999 05 06 1999 05 06 2000 12 18

0016-6731 151 3 1999 Mar Potential variance affecting homeotic Ultrabithorax and Antennapedia phenotypes in Drosophila melanogaster. 1081-91 Introgression of homeotic mutations into wild-type genetic backgrounds results in a wide variety of phenotypes and implies that major effect modifiers of extreme phenotypes are not uncommon in natural populations of Drosophila. A composite interval mapping procedure was used to demonstrate that one major effect locus accounts for three-quarters of the variance for haltere to wing margin transformation in Ultrabithorax flies, yet has no obvious effect on wild-type development. Several other genetic backgrounds result in enlargement of the haltere significantly beyond the normal range of haploinsufficient phenotypes, suggesting genetic variation in cofactors that mediate homeotic protein function. Introgression of Antennapedia produces lines with heritable phenotypes ranging from almost complete suppression to perfect antennal leg formation, as well as transformations that are restricted to either the distal or proximal portion of the appendage. It is argued that the existence of "potential" variance, which is genetic variation whose effects are not observable in wild-type individuals, is a prerequisite for the uncoupling of genetic from phenotypic divergence. Department of Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.ggibson@unity.ncsu.edu Gibson G G Wemple M M van Helden S S eng Journal Article

UNITED STATES Genetics 0374636 0 Antennapedia homeodomain protein 0 DNA Primers 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 ultrabithorax protein IM Analysis of Variance Animal Crosses, Genetic DNA Primers DNA-Binding Proteins genetics Drosophila melanogaster genetics Electrophoresis, Polyacrylamide Gel Female Genes, Homeobox physiology Genotype Homeodomain Proteins genetics Insect Proteins Male Microsatellite Repeats Phenotype Support, Non-U.S. Gov't Variation (Genetics) FBrf0049894 89276897 2499512 1989 07 21 1989 07 21 2000 12 18

0016-6731 121 2 1989 Feb Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. 333-52 In order to identify all X-linked zygotic lethal loci that exhibit a specific maternal effect on embryonic development, germline clonal analyses of X-linked zygotic lethal mutations have been performed. Two strategies were employed. In Screen A germline clonal analysis of 441 mutations at 211 previously mapped X-linked loci within defined regions was performed. In Screen B germline clonal analysis of 581 larval and pupal mutations distributed throughout the entire length of the X chromosome was performed. These approaches provide an 86% level of saturation for X-linked late zygotic lethals (larval and pupal) with specific maternal effect embryonic lethal phenotypes. The maternal effect phenotypes of these mutations are described. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115. Perrimon N N Engstrom L L Mahowald A P AP eng HD17608 HD NICHD HD23684 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Animal Clone Cells Drosophila melanogaster embryology genetics Female Genes, Lethal Homozygote Linkage (Genetics) Mutation Oogenesis Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome Zygote FBrf0059053 93268326 7684502 1993 06 23 1993 06 23 2000 12 18

0270-7306 13 6 1993 Jun Dynamic Hsp83 RNA localization during Drosophila oogenesis and embryogenesis. 3773-81 Hsp83 is the Drosophila homolog of the mammalian Hsp90 family of regulatory molecular chaperones. We show that maternally synthesized Hsp83 transcripts are localized to the posterior pole of the early Drosophila embryo by a novel mechanism involving a combination of generalized RNA degradation and local protection at the posterior. This protection of Hsp83 RNA occurs in wild-type embryos and embryos produced by females carrying the maternal effect mutations nanos and pumilio, which eliminate components of the posterior polar plasm without disrupting polar granule integrity. In contrast, Hsp83 RNA is not protected at the posterior pole of embryos produced by females carrying maternal mutations that disrupt the posterior polar plasm and the polar granules--cappuccino, oskar, spire, staufen, tudor, valois, and vasa. Mislocalization of oskar RNA to the anterior pole, which has been shown to result in induction of germ cells at the anterior, leads to anterior protection of maternal Hsp83 RNA. These results suggest that Hsp83 RNA is a component of the posterior polar plasm that might be associated with polar granules. In addition, we show that zygotic expression of Hsp83 commences in the anterior third of the embryo at the syncytial blastoderm stage and is regulated by the anterior morphogen, bicoid. We consider the possible developmental significance of this complex control of Hsp83 transcript distribution. Division of Biology, California Institute of Technology, Pasadena 91125. Ding D D Parkhurst S M SM Halsell S R SR Lipshitz H D HD eng GM40499 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Heat-Shock Proteins 63231-63-0 RNA IM Hsp83 Hsp90 Animal Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian cytology physiology Female Heat-Shock Proteins biosynthesis genetics Homozygote In Situ Hybridization Mutation Oogenesis Ovary cytology physiology RNA analysis genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0039203 83132808 6402396 1983 04 07 1983 04 07 2000 12 18

0012-1606 95 2 1983 Feb The interaction between daughterless and sex-lethal in triploids: a lethal sex-transforming maternal effect linking sex determination and dosage compensation in Drosophila melanogaster. 260-74 Regulation of Drosophila sex determination and X-chromosome dosage compensation in response to the X-chromosome/autosome (X/A) balance of the zygote is shown to require proper functioning of both the da+ gene in the mother and the Sxl+ gene in the zygote. Previous studies led to the hypothesis that zygotic Sxl+ alleles are differentially active in females (XXAA) vs males (XYAA) in response to the X/A balance, and that maternal da+ gene product acts as a positive regulator in this connection. Sxl+ activity was proposed to impose the female developmental sequence on cells which would follow the male sequence in its absence. Important predictions of this proposal are verified. This study focuses primarily on the phenotype of triploid intersexes (XXAAA, X/A = 0.67). They are shown here to survive effects of da and Sxl mutations that would be lethal to diploids. The ambiguous X/A signal of intersexes normally causes them to develop as phenotypic mosaics of male and female tissue. Loss of maternal da+ or zygotic Sxl+ gene function shifts their somatic sexual phenotype to the male alternative. A gain-of-function mutation at Sxl has the opposite effect, imposing female development regardless of the maternal genotype with respect to da. It also reduces their rate of X-linked gene expression. The effects of a duplication of Sxl+ resemble those of the constitutive Sxl allele, but are less extreme. The role of these genes in the process of X-chromosome dosage compensation is inferred indirectly from the strict dependence of the mutations' lethal effects on the X/A balance in haploids, diploids, and triploids, and more directly from the effects of the mutations on the phenotypes of the X-linked neomorphic mutations, Bar and Hairy-wing. The relationship of da+ and Sxl+ gene functions to those of other sex-specific lethal loci in D. melanogaster, and to sex determination mechanisms in other species, is discussed. Cline T W TW eng GM-23468 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 IM Animal Dosage Compensation (Genetics) Drosophila melanogaster embryology genetics Female Genes, Lethal Male Mutation Phenotype Ploidies Sex Determination (Analysis) Support, U.S. Gov't, P.H.S. Transformation, Genetic X Chromosome Zygote FBrf0149130 22038345 12021767 2002 06 03 2002 07 29 2003 02 03

1465-7392 4 6 2002 Jun Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms. 416-24 Inhibitor of apoptosis (IAP) proteins suppress apoptosis and inhibit caspases. Several IAPs also function as ubiquitin-protein ligases. Regulators of IAP auto-ubiquitination, and thus IAP levels, have yet to be identified. Here we show that Head involution defective (Hid), Reaper (Rpr) and Grim downregulate Drosophila melanogaster IAP1 (DIAP) protein levels. Hid stimulates DIAP1 polyubiquitination and degradation. In contrast to Hid, Rpr and Grim can downregulate DIAP1 through mechanisms that do not require DIAP1 function as a ubiquitin-protein ligase. Observations with Grim suggest that one mechanism by which these proteins produce a relative decrease in DIAP1 levels is to promote a general suppression of protein translation. These observations define two mechanisms through which DIAP1 ubiquitination controls cell death: first, increased ubiquitination promotes degradation directly; second, a decrease in global protein synthesis results in a differential loss of short-lived proteins such as DIAP1. Because loss of DIAP1 is sufficient to promote caspase activation, these mechanisms should promote apoptosis. Division of Biology, MC156-29, California Institute of Technology, Pasadena, CA 91125, USA. Yoo Soon Ji SJ Huh Jun R JR Muro Israel I Yu Hong H Wang Lijuan L Wang Susan L SL Feldman R M Renny RM Clem Rollie J RJ Müller H-Arno J HA Hay Bruce A BA eng GM057422-01 GM NIGMS Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Neuropeptides 0 Peptides 0 Ubiquitin 0 grim protein, Drosophila 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 reaper peptide, Drosophila EC 3.4.22.- Caspases EC 3.4.22.- DRONC caspase IM Animal Apoptosis physiology Caspases metabolism Drosophila Drosophila Proteins genetics metabolism Embryo, Nonmammalian physiology Gene Expression Regulation, Developmental Genotype In Vitro Neuropeptides metabolism Peptides metabolism RNA Processing, Post-Transcriptional physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Translation, Genetic physiology Ubiquitin metabolism FBrf0155677 22368322 12479809 2002 12 13 2003 01 10 2003 06 16

1534-5807 3 6 2002 Dec Scabrous controls ommatidial rotation in the Drosophila compound eye. 839-50 Establishment of planar polarity in the Drosophila compound eye requires precise 90 degrees rotation of the ommatidial clusters during development. We found that the morphogenetic furrow controls the stop of ommatidial rotation at 90 degrees by emitting signals to posterior ommatidial clusters. One such signal, Scabrous, is synthesized in the furrow cells and transported in vesicles to ommatidial row 6-8. Scabrous vesicles are transported through actin-based cellular extensions but not transcytosis. Scabrous functions nonautonomously to control the stop of ommatidial rotation by suppressing nemo activity in the second 45 degrees rotation. We propose that the morphogenetic furrow regulates precise ommatidial rotation by transporting Scabrous and perhaps other factors through actin-based cellular extensions. Graduate Institute of Life Sciences, National Defense Medical Center and Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Chou Ya-Hui YH Chien Cheng-Ting CT eng Journal Article

United States Dev Cell 101120028 0 Drosophila Proteins 0 Glycoproteins 0 Luminescent Proteins 0 Recombinant Fusion Proteins 133925-66-3 scabrous protein, Drosophila 147336-22-9 green fluorescent protein 22144-77-0 Cytochalasin D EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- nmo gene product IM Animal Body Patterning physiology Cell Movement physiology Cell Polarity physiology Cell Surface Extensions genetics metabolism ultrastructure Cytochalasin D pharmacology Drosophila Proteins genetics metabolism Drosophila melanogaster cytology embryology metabolism Female Gene Expression Regulation, Developmental physiology Glycoproteins genetics metabolism Luminescent Proteins diagnostic use Male Microfilaments drug effects metabolism Microscopy, Fluorescence Microtubules drug effects metabolism ultrastructure Mitogen-Activated Protein Kinases genetics metabolism Mutation physiology Photoreceptors, Invertebrate cytology embryology metabolism Protein Transport physiology Recombinant Fusion Proteins diagnostic use Support, Non-U.S. Gov't Transport Vesicles metabolism FBrf0078316 95113162 7813764 1995 02 09 1995 02 09 2002 11 01

0012-1606 166 2 1994 Dec The torso pathway in Drosophila: lessons on receptor tyrosine kinase signaling and pattern formation. 380-95 Pattern formation at the anterior and posterior termini of the Drosophila embryo involves intercellular communication via the Torso receptor tyrosine kinase (RTK). Recent advances in the understanding of Torso signaling has provided further support for the conservation of a signal transduction cassette downstream of RTKs. In addition, the analysis of the Torso pathway has begun to reveal general molecular mechanisms by which cells may impart patterning information to their neighbors through the use of RTKs. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115. Duffy J B JB Perrimon N N eng Journal Article Review Review, Academic

UNITED STATES Dev Biol 0372762 EC 2.7.1.- TOR protein, Drosophila EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor Protein-Tyrosine Kinases IM tor Animal Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Structural, Insect Morphogenesis Oogenesis Protein-Tyrosine Kinase physiology Receptor Protein-Tyrosine Kinases physiology Signal Transduction Support, Non-U.S. Gov't 88 FBrf0092564 97225217 9071590 1997 07 24 1997 07 24 2000 12 18

0016-6731 145 2 1997 Feb Beaded of Goldschmidt, an antimorphic allele of Serrate, encodes a protein lacking transmembrane and intracellular domains. 359-74 Serrate (Ser) is an essential gene in Drosophila melanogaster best known for the Ser dominant (SerD) allele and its effects on wing development. Animals heterozygous or homozygous for SerD are viable and exhibit loss of wing margin tissue and associated bristles and hairs. The Beaded of Goldschmidt (BdG) allele of Ser, when heterozygous to wild type, will also produce animals exhibiting loss of wing margin material. However, animals homozygous for BdG exhibit a larval lethal phenotype comparable to animals homozygous for loss-of-function Ser alleles. BdG is a partial duplication of the Ser locus with a single 5' Ser-homologous region and two distinct 3' regions. Meiotic recombination between BdG and a wild-type Ser chromosome demonstrated that only one DNA lesion, caused by the insertion of a transposable roo element into the coding regions of the Ser transcript, appears capable of generating BdG phenotypes. Due to the roo insertion, the protein product is predicted to be prematurely truncated and lack an extracellular cysteine-rich region along with the transmembrane and intracellular domains found within the normal SERRATE (SER) protein. The loss of these protein domains apparently contributes to the antimorphic nature of this mutation. Department of Biology, University of Rochester, New York 14627, USA. Hukriede N A NA Fleming R J RJ eng GM07102-19 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 Membrane Proteins 134324-36-0 Serrate protein 9007-49-2 DNA EC 3.1.- Ribonucleases IM Alleles Amino Acid Sequence Animal Base Sequence Binding Sites Cell Membrane DNA Drosophila melanogaster genetics ultrastructure Female Genome Insect Proteins genetics Male Membrane Proteins genetics Molecular Sequence Data Mutagenesis Recombination, Genetic Ribonucleases metabolism Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Temperature Wing FBrf0134816 21106981 11175357 2001 02 22 2001 06 07 2002 11 01

0950-9232 19 55 2000 Dec 18 Sequence and functional properties of Ets genes in the model organism Drosophila. 6409-16 Detailed molecular and genetic studies, coupled with the recent sequencing of the fly genome, have identified eight Ets-related genes in the model organism Drosophila. All show homology to genes in vertebrate species. Functional analyses of some of the Drosophila ets genes have revealed their essential roles in developmental processes such as metamorphosis, oogenesis, neurogenesis, myogenesis, and eye development. Such studies have yielded important insights into our understanding of the genetic control of hormonally-regulated gene expression, programmed cell death, and signal transduction during cell fate determination and differentiation. The developmental roles of E74 (ELF1), pointed (Ets 1), yan (TEL), and D-elg (GABPalpha) will be reviewed in this article. The context of their participation in signal transduction and gene regulation will also be discussed. The information should be of significant value to the study of related processes in higher organisms due to the growing evidence for the cross species conservation of developmental mechanisms. Center for Molecular and Structural Biology, Hollings Cancer Center, and Department of Cell Biology and Anatomy, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, South Carolina, SC 29425, USA. Hsu T T Schulz R A RA eng Journal Article Review Review, Tutorial

England Oncogene 8711562 0 Eye Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 Transcription Factors 0 anterior open protein, Drosophila 0 pointed protein 0 proto-oncogene protein ets IM Amino Acid Sequence Animal Cell Lineage Comparative Study Drosophila melanogaster genetics growth & development Eye growth & development Eye Proteins genetics physiology Gene Expression Regulation, Developmental Genes, Structural, Insect Human Insect Proteins genetics physiology Larva Metamorphosis, Biological genetics Models, Animal Molecular Sequence Data Morphogenesis genetics Multigene Family Protein Structure, Tertiary Proto-Oncogene Proteins genetics physiology Pupa Repressor Proteins genetics physiology Sequence Alignment Sequence Homology, Amino Acid Species Specificity Transcription Factors genetics physiology Vertebrates genetics 56 FBrf0144824 21869994 11880339 2002 03 06 2002 04 19

0950-1991 129 6 2002 Mar R8 development in the Drosophila eye: a paradigm for neural selection and differentiation. 1295-306 The Drosophila eye is an outstanding model with which to decipher mechanisms of neural differentiation. Paramount to normal eye development is the organized selection and differentiation of a patterned array of R8 photoreceptors - the founding photoreceptor of each ommatidium that coordinates the incorporation of all other photoreceptors. R8 development is a complex process that requires the integration of transcription factors and signaling pathways, many of which are highly conserved and perform similar functions in other species. This article discusses the developmental control of the four key elements of R8 development: selection, spacing, differentiation and orchestration of later events. New questions that have surfaced because of recent advances in the field are addressed, and the unique characteristics of R8 development are highlighted through comparisons with neural specification in other Drosophila tissues and with ganglion cell development in the mammalian retina. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Frankfort Benjamin J BJ Mardon Graeme G eng EY02520 EY NEI R01 EY11232-01 EY NEI Journal Article Review Review, Tutorial

England Development 8701744 IM Animal Cell Differentiation Drosophila melanogaster Eye cytology embryology Peripheral Nervous System cytology embryology physiology Photoreceptors, Invertebrate cytology embryology physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 91 FBrf0149011 22013861 12019232 2002 05 20 2002 12 20

0016-6731 161 1 2002 May Genetic control of cuticle formation during embryonic development of Drosophila melanogaster. 171-82 The embryonic cuticle of Drosophila melanogaster is deposited by the epidermal epithelium during stage 16 of development. This tough, waterproof layer is essential for maintaining the structural integrity of the larval body. We have characterized mutations in a set of genes required for proper deposition and/or morphogenesis of the cuticle. Zygotic disruption of any one of these genes results in embryonic lethality. Mutant embryos are hyperactive within the eggshell, resulting in a high proportion reversed within the eggshell (the "retroactive" phenotype), and all show poor cuticle integrity when embryos are mechanically devitellinized. This last property results in embryonic cuticle preparations that appear grossly inflated compared to wild-type cuticles (the "blimp" phenotype). We find that one of these genes, krotzkopf verkehrt (kkv), encodes the Drosophila chitin synthase enzyme and that a closely linked gene, knickkopf (knk), encodes a novel protein that shows genetic interaction with the Drosophila E-cadherin, shotgun. We also demonstrate that two other known mutants, grainy head (grh) and retroactive (rtv), show the blimp phenotype when devitellinized, and we describe a new mutation, called zeppelin (zep), that shows the blimp phenotype but does not produce defects in the head cuticle as the other mutations do. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA. Ostrowski Stephen S Dierick Herman A HA Bejsovec Amy A eng GM-59068 GM NIGMS Journal Article

United States Genetics 0374636 0 Benzamides 0 Cadherins 103055-07-8 fluphenacur 1398-61-4 Chitin EC 2.4.1.16 Chitin Synthase IM Amino Acid Sequence Animal Benzamides metabolism Cadherins genetics Chitin biosynthesis Chitin Synthase antagonists & inhibitors genetics Chromosome Mapping Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Molecular Sequence Data Mutation Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0152256 22194806 12145660 2002 09 02 2002 09 27

1061-4036 32 1 2002 Sep Distinct in vivo requirements for establishment versus maintenance of transcriptional repression. 206-10 Low-level ectopic expression of the Runt transcription factor blocks activation of the Drosophila melanogaster segmentation gene engrailed (en) in odd-numbered parasegments and is associated with a lethal phenotype. Here we show, by using a genetic screen for maternal factors that contribute in a dose-dependent fashion to Runt-mediated repression, that there are two distinct steps in the repression of en by Runt. The initial establishment of repression is sensitive to the dosage of the zinc-finger transcription factor Tramtrack. By contrast, the co-repressor proteins Groucho and dCtBP, and the histone deacetylase Rpd3, do not affect establishment but instead maintain repression after the blastoderm stage. The distinction between establishment and maintenance is confirmed by experiments with Runt derivatives that are impaired specifically for either co-repressor interaction or DNA binding. Other transcription factors can also establish repression in Rpd3-deficient embryos, which indicates that the distinction between establishment and maintenance may be a general feature of eukaryotic transcriptional repression. Department of Biochemistry and Cell Biology and the Center for Developmental Genetics, Stony Brook University, Stony Brook, New York 11794-5140, USA. Wheeler John C JC VanderZwan Christine C Xu Xiaoti X Swantek Deborah D Tracey W Daniel WD Gergen J Peter JP eng Journal Article

United States Nat Genet 9216904 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Homeodomain Proteins 0 Repressor Proteins 0 Runt protein 0 Transcription Factors 0 engrail protein, Drosophila 0 groucho protein 0 tramtrack protein 144714-44-3 RPD3 protein IM Nat Genet. 2002 Sep;32(1):87-8 12145661 Animal DNA-Binding Proteins metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster genetics Female Gene Expression Regulation physiology Gene Silencing physiology Homeodomain Proteins genetics Male Repressor Proteins metabolism Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism FBrf0090495 97053793 8898207 1996 12 16 1996 12 16 2002 11 08

0092-8674 87 3 1996 Nov 1 Dual roles for patched in sequestering and transducing Hedgehog. 553-63 Secreted proteins of the Hedgehog (Hh) family have diverse organizing roles in animal development. Recently, a serpentine protein Smoothened (Smo) has been proposed as a Hh receptor. Here, we present evidence that implicates another multiple-pass transmembrane protein, Patched (Ptc), in Hh reception and suggests a novel signal transduction mechanism in which Hh binds to Ptc, or a Ptc-Smo complex, and thereby induces Smo activity. Our results also show that Ptc limits the range of Hh action; we provide evidence that high levels of Ptc induced by Hh serve to sequester any free Hh and therefore create a barrier to its further movement. Howard Hughes Medical Institute, Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. Chen Y Y Struhl G G eng Journal Article

UNITED STATES Cell 0413066 0 Insect Hormones 0 Insect Proteins 0 Macromolecular Systems 0 Membrane Proteins 0 Proteins 0 Receptors, Cell Surface 0 dpp protein, Drosophila 0 patched protein, Drosophila 0 smoothened protein 149291-21-4 hedgehog protein, Drosophila IM Alleles Animal Animals, Genetically Modified Drosophila melanogaster embryology genetics growth & development Gene Expression Regulation, Developmental Insect Hormones genetics physiology Insect Proteins physiology Macromolecular Systems Membrane Proteins genetics physiology Models, Biological Multigene Family Proteins genetics metabolism Receptors, Cell Surface genetics physiology Signal Transduction physiology Support, Non-U.S. Gov't Wing abnormalities embryology growth & development FBrf0056240 92201645 1551580 1992 04 28 1992 04 28 2000 12 18

0016-6731 130 3 1992 Mar Evidence of a dual function in fl(2)d, a gene needed for Sex-lethal expression in Drosophila melanogaster. 597-612 In Drosophila melanogaster, the female sexual development of the soma and the germline requires the activity of the gene Sxl. The somatic cells need the function of the gene fl(2)d to follow the female developmental pathway, due to its involvement in the female-specific splicing of Sxl RNA. Here we report the analysis of both fl(2)d1 and fl(2)d2 mutations: (1) fl(2)d1 is a temperature-sensitive mutation lethal in females and semilethal in males; (2) fl(2)d2 is lethal in both sexes; (3) the fl(2)d1/fl(2)d2 constitution is temperature-sensitive and lethal in females, while semilethal in males. The temperature-sensitive period of fl(2)d1 in females expands the whole development. SxlM1 partially suppresses the lethality of fl(2)d1 homozygous females and that of fl(2)d1/fl(2)d2 constitution, whereas it does not suppress the lethality of fl(2)d2 homozygous females. The addition of extra Sxl+ copies does not increase the suppression effect of SxlM1. The fl(2)d1 mutation in homozygosis and the fl(2)d1/fl(2)d2 constitution, but not the fl(2)d2 in homozygosis, partially suppress the lethality of SxlM1 males. This suppression is not prevented by the addition of extra Sxl+ copies. The semilethality of both fl(2)d1 and fl(2)d1/fl(2)d2 males, and the lethality of fl(2)d2 males, is independent of Sxl function. There is no female synergistic lethality between mutations at fl(2)d and neither at sc or da. However, the female synergistic lethality between mutations at Sxl and either sc or da is increased by fl(2)d mutations. We have analyzed the effect of the fl(2)d mutations on the germline development of both females and males. For that purpose, we carried out the clonal analysis of fl(2)d1 in the germline. In addition, pole cells homozygous for fl(2)d2 were transplanted into wild-type host embryos, and we checked whether the mutant pole cells were capable of forming functional gametes. The results indicated that fl(2)d mutant germ cells cannot give rise to functional oocytes, while they can form functional sperm. Moreover, SxlM1 suppresses the sterility of the fl(2)d1 homozygous females developing at the permissive temperature. Thus, with respect to the development of the germline the fl(2)d mutations mimic the behavior of loss-of-function mutations at the gene Sxl. Females double heterozygous for fl(2)d and snf1621 are fully viable and fertile. fl(2)d2 in heterozygosis partially suppresses the phenotype of female germ cells homozygous for snf1621; however, this is not the case with the fl(2)d1 mutation. The fl(2)d mutations partially suppress the phenotype of the female germ cells homozygous for ovoDIrSI.(ABSTRACT TRUNCATED AT 400 WORDS) Centro de Investigaciones Biológicas, Madrid, Spain. Granadino B B San Juán A A Santamaria P P Sánchez L L eng Journal Article

UNITED STATES Genetics 0374636 IM Sxl fl(2)d ovo Animal Clone Cells Dosage Compensation (Genetics) Drosophila melanogaster cytology genetics Female Gene Expression Regulation genetics Genes, Lethal Kinetics Larva cytology Male Mutation Phenotype Sex Determination (Analysis) Support, Non-U.S. Gov't Suppression, Genetic Temperature FBrf0123143 20078086 10611962 2000 01 21 2000 01 21 2001 11 14

1081-0706 15 1999 Visual transduction in Drosophila. 231-68 The Drosophila phototransduction cascade has emerged as an attractive paradigm for understanding the molecular mechanisms underlying visual transduction, as well as other G protein-coupled signaling cascades that are activated and terminated with great rapidity. A large collection of mutants affecting the fly visual cascade have been isolated, and the nature and function of many of the affected gene products have been identified. Virtually all of the proteins, including those that were initially classified as novel, are highly related to vertebrate homologs. Recently, it has become apparent that most of the proteins central to Drosophila phototransduction are coupled into a supramolecular signaling complex, signalplex, through association with a PDZ-containing scaffold protein. The characterization of this complex has led to a re-evaluation of the mechanisms underlying the activation and deactivation of the phototransduction cascade. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. cmontell@jhmi.edu Montell C C eng Journal Article Review Review, Academic

UNITED STATES Annu Rev Cell Dev Biol 9600627 0 Cations 7440-70-2 Calcium 9009-81-8 Rhodopsin IM S Animal Calcium metabolism Cations Drosophila melanogaster genetics metabolism physiology Human Light Phototransduction physiology Rhodopsin metabolism Support, U.S. Gov't, P.H.S. 183 FBrf0074348 94277102 7516476 1994 07 18 1994 07 18 2002 11 01

0270-7306 14 7 1994 Jul RNA binding by Sxl proteins in vitro and in vivo. 4975-90 Sxl has been proposed to regulate splicing of specific target genes by directly interacting with their pre-mRNAs. We have therefore examined the RNA-binding properties of Sxl protein in vitro and in vivo. Gel shift and UV cross-linking assays with a purified recombinant MBP-Sxl fusion protein demonstrated preferential binding to RNAs containing poly(U) tracts, and the protein footprinted over the poly(U) region. The protein did not appear to recognize either branch point or AG dinucleotide sequences, but an adenosine residue at the 5' end of the poly(U) tract enhanced binding severalfold. MBP-Sxl formed two shifted complexes on a tra regulated acceptor site RNA; the doubly shifted form may have been stabilized by protein-protein interactions. Consistent with its proposed role in pre-mRNA processing, in nuclear extracts Sxl was found in large ribonucleoprotein (RNP) complexes which sedimented significantly faster than bulk heterogeneous nuclear RNP and small nuclear RNPs. Anti-Sxl staining of polytene chromosomes showed Sxl protein at a number of chromosomal locations, among which was the Sxl locus itself. Sxl protein could also be targeted to a new chromosomal site carrying a transgene containing splicing regulatory sequences from the Sxl gene, following transcriptional induction. After prolonged heat shock, all Sxl protein was restricted to the heat-induced puff at the hs93D locus. In contrast, a presumptive small nuclear RNP protein was observed at several heat puffs following shock. Department of Molecular Biology, Princeton University, New Jersey 08544. Samuels M E ME Bopp D D Colvin R A RA Roscigno R F RF Garcia-Blanco M A MA Schedl P P eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Heterogeneous-Nuclear Ribonucleoproteins 0 Insect Hormones 0 Oligoribonucleotides 0 RNA Precursors 0 RNA-Binding Proteins 0 Recombinant Fusion Proteins 0 Ribonucleoproteins 0 Ribonucleoproteins, Small Nuclear 0 Sxl protein, Drosophila 63231-63-0 RNA IM Sxl Animal Base Sequence Binding Sites Binding, Competitive Cell Line Cell Nucleus metabolism Chromosomes metabolism ultrastructure Drosophila melanogaster genetics metabolism Heterogeneous-Nuclear Ribonucleoproteins Insect Hormones biosynthesis metabolism Kinetics Molecular Sequence Data Oligoribonucleotides metabolism pharmacology RNA biosynthesis metabolism RNA Precursors metabolism RNA Processing, Post-Transcriptional RNA Splicing RNA-Binding Proteins metabolism Recombinant Fusion Proteins metabolism Ribonucleoproteins metabolism Ribonucleoproteins, Small Nuclear metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0102844 98250685 9584098 1998 07 07 1998 07 07 2000 12 18

0016-6731 149 1 1998 May Genes expressed in the ring gland, the major endocrine organ of Drosophila melanogaster. 217-31 We have used an enhancer-trap approach to begin characterizing the function of the Drosophila endocrine system during larval development. Five hundred and ten different lethal PZ element insertions were screened to identify those in which a reporter gene within the P element showed strong expression in part or all of the ring gland, the major site of production and release of developmental hormones, and which had a mutant phenotype consistent with an endocrine defect. Nine strong candidate genes were identified in this screen, and eight of these are expressed in the lateral cells of the ring gland that produce ecdysteroid molting hormone (EC). We have confirmed that the genes detected by these enhancer traps are expressed in patterns similar to those detected by the reporter gene. Two of the genes encode proteins, protein kinase A and calmodulin, that have previously been implicated in the signaling pathway leading to EC synthesis and release in other insects. A third gene product, the translational elongation factor EF-1alpha F1, could play a role in the translational regulation of EC production. The screen also identified the genes couch potato and tramtrack, previously known from their roles in peripheral nervous system development, as being expressed in the ring gland. One enhancer trap revealed expression of the gene encoding the C subunit of vacuolar ATPase (V-ATPase) in the medial cells of the ring gland, which produce the juvenile hormone that controls progression through developmental stages. This could reveal a function of V-ATPase in the response of this part of the ring gland to adenotropic neuropeptides. However, the gene identified by this enhancer trap is ubiquitously expressed, suggesting that the enhancer trap is detecting only a subset of its control elements. The results show that the enhancer trap approach can be a productive way of exploring tissue-specific genetic functions in Drosophila. Developmental Biology Center, University of California, Irvine, California 92697-2275, USA. Harvie P D PD Filippova M M Bryant P J PJ eng GM-07134 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 2.7.7.- Transposase EC 3.2.1.23 beta-Galactosidase IM Amino Acid Sequence Animal Drosophila melanogaster genetics Endocrine Glands chemistry Genes, Reporter Genetic Techniques In Situ Hybridization Molecular Sequence Data Phenotype Promoter Regions (Genetics) Sequence Alignment Signal Transduction genetics Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transposase genetics beta-Galactosidase genetics FBrf0088313 96196408 8608939 1996 05 30 1996 05 30 2003 01 30

0890-9369 10 8 1996 Apr 15 Repression and activation by multiprotein complexes that alter chromatin structure. 905-20 Recent studies have provided strong evidence that macromolecular complexes are used in the cell to remodel chromatin structure during activation and to create an inaccessible structure during repression, Although there is not yet any rigorous demonstration that modification of chromatin structure plays a direct, causal role in either activation or repression, there is sufficient smoke to indicate the presence of a blazing inferno nearby. It is clear that complexes that remodel chromatin are tractable in vitro; hopefully this will allow the establishment of systems that provide a direct analysis of the role that remodeling might play in activation. These studies indicate that establishment of functional systems to corroborate the elegant genetic studies on repression might also be tractable. As the mechanistic effects of these complexes are sorted out, it will become important to understand how the complexes are regulated. In many of the instances discussed above, the genes whose products make up these complexes were identified in genetic screens for effects on developmental processes. This implies a regulation of the activity of these complexes in response to developmental cues and further implies that the work to fully understand these complexes will occupy a generation of scientists. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA. Kingston R E RE Bunker C A CA Imbalzano A N AN eng Journal Article Review Review, Academic

UNITED STATES Genes Dev 8711660 0 CYC8 protein, S cerevisiae 0 Chromatin 0 DNA-Binding Proteins 0 Fungal Proteins 0 Macromolecular Systems 0 Nucleosomes 0 Repressor Proteins 0 Ribonucleoprotein, U1 Small Nuclear 0 SNF protein 0 SWI1 protein 0 Transcription Factors 56-65-5 Adenosine Triphosphate IM Adenosine Triphosphate physiology Animal Chromatin ultrastructure DNA-Binding Proteins physiology Drosophila melanogaster genetics Fungal Proteins physiology Gene Expression Regulation Macromolecular Systems Nucleosomes physiology ultrastructure Repressor Proteins physiology Ribonucleoprotein, U1 Small Nuclear genetics Saccharomyces cerevisiae genetics Telomere Transcription Factors physiology Transcription, Genetic 145 FBrf0110050 99394849 10466937 1999 10 13 1999 10 13 2003 06 16

0012-1592 41 4 1999 Aug Mitochondrial small ribosomal RNA is present on polar granules in early cleavage embryos of Drosophila melanogaster. 495-502 In Drosophila, formation of the germline progenitors, the pole cells, is induced by polar plasm localized in the posterior pole region of early embryos. The polar plasm contains polar granules, which act as a repository for the factors required for pole cell formation. It has been postulated that the factors are stored as mRNA and are later translated on polysomes attached to the surface of polar granules. Here, the identification of mitochondrial small ribosomal RNA (mtsrRNA) as a new component of polar granules is described. The mtsrRNA was enriched in the polar plasm of the embryos immediately after oviposition and remained in the polar plasm throughout the cleavage stage until pole cell formation. In situ hybridization at an ultrastructural level revealed that mtsrRNA was enriched on the surface of polar granules in cleavage embryos. Furthermore, the localization of mtsrRNA in the polar plasm depended on the normal function of oskar, vasa and tudor genes, which are all required for pole cell formation. The temporal and spatial distribution of mtsrRNA is essentially identical to that of mitochondrial large ribosomal RNA (mtlrRNA), which has been shown to be required for pole cell formation. Taken together, it is speculated that mtsrRNA and mtlrRNA are part of the translation machinery localized to polar granules, which is essential for pole cell formation. Institute of Biological Sciences, University of Tsukuba, Ibaraki, Japan. Kashikawa M M Amikura R R Nakamura A A Kobayashi S S eng Journal Article

JAPAN Dev Growth Differ 0356504 0 Insect Proteins 0 RNA, Ribosomal 0 RNA, mitochondrial 0 oskar protein, Drosophila 63231-63-0 RNA IM Animal Cell Polarity Drosophila melanogaster embryology metabolism Embryo, Nonmammalian metabolism ultrastructure Germ Cells cytology In Situ Hybridization Insect Proteins genetics metabolism Microscopy, Electron RNA metabolism RNA, Ribosomal metabolism Support, Non-U.S. Gov't FBrf0044470 86275949 3089870 1986 09 18 1986 09 18 2000 12 18

0016-6731 113 3 1986 Jul X-linked female-sterile loci in Drosophila melanogaster. 695-712 We have examined the number of X-linked loci specifically required only during oogenesis. Complementation analyses among female-sterile (fs) mutations obtained in two mutagenesis screens--GANS' and MOHLER's--indicate that any fs locus represented by two or more mutant alleles in GANS' collection are usually present in MOHLER's collection. However, when a locus is represented by a single allele in one collection, it is generally not present in the other collection. We propose that this discrepancy is due to the fact that most "fs loci" represented by less than two mutant alleles are, in fact, vital (zygotic lethal) genes, and that the fs alleles are hypomorphic mutations of such genes. In support of this hypothesis we have identified lethal alleles at 12 of these "fs loci." The present analysis has possibly identified all maternal-effect lethal loci detectable by mutations on the X chromosome and has allowed us to reevaluate the number of "ovary-specific fs" loci in the Drosophila genome. Finally, germline clone analysis of a large number of fs mutations was performed in order to estimate the relative contribution of germline and somatic cell derivatives to oogenesis and to embryonic development. All the maternal-effect lethal loci tested are germline-dependent. Perrimon N N Mohler D D Engstrom L L Mahowald A P AP eng HD-17607 HD NICHD HD-17608 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Chromosome Mapping Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Female Genetic Complementation Test Infertility, Female Oogenesis Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome FBrf0078203 95203684 7896097 1995 04 26 1995 04 26 2002 10 21

0016-6731 138 4 1994 Dec Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster. 1151-62 The Polycomb (Pc) group genes of Drosophila are negative regulators of homeotic genes, but individual loci have pleiotropic phenotypes. It has been suggested that Pc group genes might form a regulatory hierarchy, or might be members of a multimeric complex that obeys the law of mass action. Recently, it was shown that polyhomeotic (ph) immunoprecipitates in a multimeric complex that includes Pc. Here, we show that duplications of ph suppress homeotic transformations of Pc and Pcl, supporting a mass-action model for Pc group function. We crossed ph alleles to all members of the Polycomb group, and to E(Pc) and Su(z)2 to look for synergistic effects. We observed extragenic noncomplementation between ph503 and Pc, Psc1 and Su(z)2(1) in females, and between ph409 and Sce1, ScmD1 and E(z)1 mutations in males, suggesting that these gene products might interact directly with ph. Males hemizygous for a temperature-sensitive allele, ph2, are lethal when heterozygous with mutants in Asx, Pc, Pcl, Psc, Sce and Scm, and with E(Pc) and Su(z)2. Mutations in trithorax group genes were not able to suppress the lethality of ph2/Y; Psc1/+ males. ph2 was not lethal with extra sex combs, E(z), super sex combs (sxc) or l(4)102EFc heterozygotes, but did cause earlier lethality in embryos homozygous for E(z), sxc and l(4)102EFc. However, ph503 did not enhance homeotic phenotypes of esc heterozygotes derived from homozygous esc- mothers. We examined the embryonic phenotypes of ph2 embryos that were lethal when heterozygous or homozygous for other mutations. Based on this phenotypic analysis, we suggest that ph may perform different functions in conjunction with differing subsets of Pc group genes. Department of Zoology, University of British Columbia, Vancouver, Canada. Cheng N N NN Sinclair D A DA Campbell R B RB Brock H W HW eng Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Macromolecular Systems 0 Nucleoproteins 0 Proteins 134549-01-2 Polycomb protein, insect 146888-72-4 polyhomeotic protein, Drosophila IM Alleles Animal DNA-Binding Proteins genetics physiology Drosophila melanogaster embryology genetics ultrastructure Embryo, Nonmammalian growth & development ultrastructure Female Gene Dosage Genes, Homeobox Genes, Insect Genes, Lethal Macromolecular Systems Male Models, Genetic Multigene Family Nucleoproteins genetics physiology Phenotype Proteins genetics physiology Support, Non-U.S. Gov't FBrf0091093 97108746 8951067 1997 01 23 1997 01 23 2000 12 18

0950-1991 122 11 1996 Nov Ectopic expression of wingless in imaginal discs interferes with decapentaplegic expression and alters cell determination. 3519-29 We have expressed the segment polarity gene wingless (wg) ectopically in imaginal discs to examine its regulation of both ventral patterning and transdetermination. By experimentally manipulating the amount of Wg protein, we show that different thresholds of Wg activity elicit different outcomes, which are mediated by regulation of decapentaplegic (dpp) expression and result in alterations in the expression of homeotic genes. A high level of Wg activity leads to loss of all dorsal pattern elements and the formation of a complete complement of ventral pattern elements on the dorsal side of legs, and is correlated with repression of dpp expression. wg expression in dorsal cells of each disc also leads to dose-dependent transdetermination in those cells in homologous discs such as the labial, antennal and leg, but not in cells of dorsally located discs. When dpp expression is repressed by high levels of Wg, transdetermination does not occur, confirming that dpp participates with wg to induce transdetermination. These and other experiments suggest that dorsal expression of wg alters disc patterning and disc cell determination by modulating the expression of dpp. The dose-dependent effects of wg on dpp expression, ventralization of dorsal cells and transdetermination support a model in which wg functions as a morphogen in imaginal discs. Department of Zoology, University of Washington, Seattle 98195-1800, USA. lajohnst@fred.fhcrc.org Johnston L A LA Schubiger G G eng F32 GM17373 GM NIGMS RO1 GM33656 GM NIGMS Journal Article

ENGLAND Development 8701744 0 Homeodomain Proteins 0 Insect Hormones 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 dpp protein, Drosophila 0 engrail protein, Drosophila 117758-26-6 wingless protein, Drosophila IM Animal Body Patterning Cell Differentiation Cell Division Drosophila melanogaster embryology Extremities embryology Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins physiology Insect Hormones physiology Insect Proteins genetics Proto-Oncogene Proteins physiology Support, U.S. Gov't, P.H.S. Transcription Factors physiology Wing embryology FBrf0055014 92020874 1924306 1991 10 31 1991 10 31 2000 12 18

0027-8424 88 19 1991 Oct 1 Identification and partial characterization of six members of the kinesin superfamily in Drosophila. 8470-4 Recent evidence has suggested that the principal polypeptide component of the microtubule motor protein kinesin may be a member of an extended superfamily of related motor proteins. To gain insight into how large the kinesin superfamily might be and to begin determining the potential functions in which various superfamily members might participate, we identified and partially characterized six additional members of the Drosophila kinesin superfamily. Genes encoding these proteins were identified by using the polymerase chain reaction with degenerate primers corresponding to highly conserved regions of the kinesin heavy-chain motor domain. Partial sequencing of the six genes revealed that they encode proteins that are 40-60% identical to the motor domain of the kinesin heavy-chain sequence. The cytogenetic locations as well as the developmental and tissue-specific expression patterns have been determined. The data suggest that each of these six kinesin-like proteins may have functions in a wide variety of cell types and tissues. Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138. Stewart R J RJ Pesavento P A PA Woerpel D N DN Goldstein L S LS eng GENBANK M74427 M74428 M74429 M74430 M74431 M74432 M94198 M94199 M94200 X53420 GM35252 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Microtubule Proteins 0 Oligonucleotides 0 RNA, Messenger EC 3.6.1.- Kinesin IM KAR3 KHC KLP1 KLP2 KLP3 KLP4 KLP5 KLP6 bimC cut7 ncd nod unc104 Age Factors Amino Acid Sequence Animal Base Sequence Blotting, Northern Chromosome Mapping Drosophila melanogaster genetics Gene Expression Genes, Structural Kinesin genetics Microtubule Proteins genetics Molecular Sequence Data Multigene Family Oligonucleotides chemistry Polymerase Chain Reaction RNA, Messenger genetics Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0128675 20323175 10862750 2000 08 28 2000 08 28 2002 04 19

0950-1991 127 14 2000 Jul Nuclear import of cubitus interruptus is regulated by hedgehog via a mechanism distinct from Ci stabilization and Ci activation. 3131-9 The Hedgehog (Hh) signal is transduced via Cubitus interruptus (Ci) to specify cell fates in the Drosophila wing. In the absence of Hh, the 155 kDa full-length form of Ci is cleaved into a 75 kDa repressor. Hh inhibits the proteolysis of full-length Ci and facilitates its conversion into an activator. Recently, it has been suggested that Hh promotes Ci nuclear import in tissue culture cells. We have studied the mechanism of Ci nuclear import in vivo and the relationship between nuclear import, stabilization and activation. We found that Ci rapidly translocates to the nucleus in cells close to the anteroposterior (AP) boundary and this rapid nuclear import requires Hh signaling. The nuclear import of Ci is regulated by Hh even under conditions in which Ci is fully stabilized. Furthermore, cells that exhibit Ci stabilization and rapid nuclear import do not necessarily exhibit maximal Ci activity. It has been previously shown that stabilization does not suffice for activation. Consistent with this finding, our results suggest that the mechanisms regulating nuclear import, stabilization and activation are distinct from each other. Finally, we show that cos2 and pka, two molecules that have been characterized primarily as negative regulators of Ci activity, also have positive roles in the activation of Ci in response to Hh. Department of Biochemistry, Molecular Biology and Cell Biology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois 60208, USA. Wang Q T QT Holmgren R A RA eng GM057450 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 costal2 protein 0 cubitus interruptus protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 3.6.1.- Kinesin IM Animal Biological Transport Body Patterning Cell Nucleus metabolism Cyclic AMP-Dependent Protein Kinases metabolism DNA-Binding Proteins metabolism Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Insect Proteins genetics metabolism Kinesin metabolism Organ Culture Phosphorylation Protein-Serine-Threonine Kinases metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Wing growth & development FBrf0054122 92146935 1686006 1992 03 13 1992 03 13 2000 12 18

0016-6731 129 4 1991 Dec Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. 1111-7 Evolutionary processes can be inferred from comparisons of intraspecific polymorphism and interspecific divergence. We sequenced a 1.1-kb fragment of the cubitus interruptus Dominant (ciD) locus located on the nonrecombining fourth chromosome for ten natural lines of Drosophila melanogaster and nine of Drosophila simulans. We found no polymorphism within D. melanogaster and a single polymorphism within D. simulans; divergence between the species was about 5%. Comparison with the alcohol dehydrogenase gene and its two flanking regions in D. melanogaster, for which comparable data are available, revealed a statistically significant departure from neutrality in all three tests. This lack of polymorphism in the ciD locus may reflect recent positive selective sweeps on the fourth chromosome with extreme hitchhiking generated by the lack of recombination. By simulation, we estimate there to be a 50% chance that the selective sweeps occurred within the past 30,000 years in D. melanogaster and 75,000 in D. simulans. Department of Ecology and Evolutionary Biology, Princeton University, New Jersey 08544. Berry A J AJ Ajioka J W JW Kreitman M M eng GM 39355 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 1.1.1.1 Alcohol Dehydrogenase IM Adh Alcohol Dehydrogenase genetics metabolism Animal Chromosomes Drosophila enzymology genetics Drosophila melanogaster enzymology genetics Polymorphism, Restriction Fragment Length Recombination, Genetic Selection (Genetics) Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Variation (Genetics) FBrf0053790 91372138 1680045 1991 10 24 1991 10 24 2000 12 18

0950-1991 111 2 1991 Feb Molecular definition of the morphogenetic and regulatory functions and the cis-regulatory elements of the Drosophila Abd-B homeotic gene. 393-405 The Abdominal-B (Abd-B) gene, a member of the Drosophila bithorax complex, is required during development to specify the identity of parasegments 10-14. Based on genetic studies, Casanova, J., Sánchez-Herrero, E. and Morata, G. (1986) Cell 47, 627-636, proposed that the Abd-B gene consists of two distinct elements that provide a morphogenetic (m) function in PS 10-13 and a regulatory (r) function in PS 14, where it represses m function. Here we present molecular confirmation of this genetic model. Using specific antibodies, we show that the 55 X 10(3) M(r) and 30 X 10(3) M(r) Abd-B proteins, predicted by cDNA analysis, are indeed present in PS 10-13 and PS 14, respectively. We also examine Abd-B mRNA and protein expression patterns in embryos mutant for either the m or r function. These data allow us to unambiguously assign m function to the 55 X 10(3) M(r) protein and r function to the 30 X 10(3) M(r) protein. Furthermore, as postulated by the model, transcription of the mRNA encoding the m protein is derepressed in PS 14 in the absence of r function. We have also studied the effect of mutations mapping in the infra-abdominal (iab) region located downstream of the Abd-B gene. Genetic studies suggest that the iab region contains cis-acting regulatory elements controlling Abd-B expression in PS 10-12. We present molecular evidence for the presence of downstream cis-regulatory elements by analyzing Abd-B mRNA and protein patterns in iab-6 and iab-7 embryos. Our analysis reveals the presence of parasegment and cell-specific regulatory elements of the Abd-B gene within each iab region. The Abd-B gene may provide a model for the understanding of similarly complex homeotic genes in higher organisms. Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84132. Boulet A M AM Lloyd A A Sakonju S S eng Journal Article

ENGLAND Development 8701744 IM Abd-B Animal Blotting, Western Chromosome Mapping Drosophila melanogaster genetics Gene Expression physiology Genes, Homeobox physiology Genes, Regulator physiology Microscopy, Immunoelectron Morphogenesis genetics Mutation genetics FBrf0149131 22038346 12021768 2002 06 03 2002 07 29 2003 02 03

1465-7392 4 6 2002 Jun Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1. 425-31 Inhibitor of apoptosis proteins (IAPs) provide a critical barrier to inappropriate apoptotic cell death through direct binding and inhibition of caspases. We demonstrate that degradation of IAPs is an important mechanism for the initiation of apoptosis in vivo. Drosophila Morgue, a ubiquitin conjugase-related protein, promotes DIAP1 down-regulation in the developing retina to permit selective programmed cell death. Morgue complexes with DIAP1 in vitro and mediates DIAP1 degradation in a manner dependent on the Morgue UBC domain. Reaper (Rpr) and Grim, but not Hid, also promote the degradation of DIAP1 in vivo, suggesting that these proteins promote cell death through different mechanisms. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue; Campus Box 8103, Saint Louis, MO 63110, USA. Hays Rebecca R Wickline Laura L Cagan Ross R eng GENBANK AF145603 EY13507 EY NEI R01EY11495 EY NEI Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Eye Proteins 0 Neuropeptides 0 Peptides 0 Ubiquitin 0 grim protein, Drosophila 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 morgue protein, Drosophila 0 reaper peptide, Drosophila EC 6. Ligases EC 6.3.2.- ubiquitin-conjugating enzyme E2 IM Amino Acid Sequence Animal Apoptosis physiology Cells, Cultured Chromosome Mapping Chromosomes Conserved Sequence Drosophila Proteins genetics metabolism Drosophila melanogaster Eye Proteins genetics metabolism Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic In Vitro Ligases genetics Molecular Sequence Data Neuropeptides metabolism Peptides metabolism Photoreceptors, Invertebrate cytology embryology enzymology Retina cytology embryology enzymology Support, U.S. Gov't, P.H.S. Ubiquitin metabolism FBrf0160375 22719052 12835400 2003 07 01 2003 09 30

0950-1991 130 16 2003 Aug Integrins modulate Sog activity in the Drosophila wing. 3851-64 Morphogenesis of the Drosophila wing depends on a series of cell-cell and cell-extracellular matrix interactions. During pupal wing development, two secreted proteins, encoded by the short gastrulation (sog) and decapentaplegic (dpp) genes, vie to position wing veins in the center of broad provein territories. Expression of the Bmp4 homolog dpp in vein cells is counteracted by expression of the Bmp antagonist sog in intervein cells, which results in the formation of straight veins of precise width. We screened for genetic interactions between sog and genes encoding a variety of extracellular components and uncovered interactions between sog and myospheroid (mys), multiple edematous wing (mew) and scab (scb), which encode betaPS, alphaPS1 and alphaPS3 integrin subunits, respectively. Clonal analysis reveals that integrin mutations affect the trajectory of veins inside the provein domain and/or their width and that misexpression of sog can alter the behavior of cells in such clones. In addition, we show that a low molecular weight form of Sog protein binds to alphaPS1betaPS. We find that Sog can diffuse from its intervein site of production into adjacent provein domains, but only on the dorsal surface of the wing, where Sog interacts functionally with integrins. Finally, we show that Sog diffusion into provein regions and the reticular pattern of extracellular Sog distribution in wild-type wings requires mys and mew function. We propose that integrins act by binding and possibly regulating the activity/availability of different forms of Sog during pupal development through an adhesion independent mechanism. Departamento de Histologia e Embriologia, Universidade Federal do Rio de Janeiro, 21941-970, Rio de Janeiro, Brazil. haraujo@histo.ufrj.br Araujo Helena H Negreiros Erika E Bier Ethan E eng R01 NS 29870 NS NINDS Journal Article

England Development 8701744 0 Bone Morphogenetic Proteins 0 Drosophila Proteins 0 Integrins 0 sog protein, Drosophila IM Animal Bone Morphogenetic Proteins metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics metabolism Embryonic Structures cytology metabolism Extracellular Matrix metabolism In Situ Hybridization Integrins genetics metabolism Morphogenesis Phenotype Signal Transduction physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Wing embryology physiology FBrf0075068 94329526 7914367 1994 09 02 1994 09 02 2003 06 16

0027-8424 91 16 1994 Aug 2 A differential response element for the homeotics at the Antennapedia P1 promoter of Drosophila. 7420-4 Homeotic genes encode DNA-binding transcription factors that specify the identity of a segment or segments in particular body regions of Drosophila. The developmental specificity of these proteins results from their differential regulation of various target genes. This specificity could be achieved by use of different regulatory elements by the homeoproteins or by use of the same elements in different ways. The Ultrabithorax (UBX), abdominal-A (ABD-A), and Antennapedia (ANTP) homeoproteins differentially regulate the Antennapedia P1 promoter in a cell culture cotransfection assay: UBX and ABD-A repress, whereas ANTP activates P1. Either of two regions of P1 can confer this pattern of differential regulation. One of the regions lies downstream and contains homeoprotein-binding sites flanking a 37-bp region called BetBS. ANTP protein activates transcription through the binding sites, whereas UBX and ABD-A both activate transcription through BetBS and use the flanking binding sites to prevent this effect. Thus, homeoproteins can use the same regulatory element but in very different ways. Chimeric UBX-ANTP proteins and UBX deletion derivatives demonstrate that functional specificity in P1 regulation is dictated mainly by sequences outside the homeodomain, with important determinants in the N-terminal region of the proteins. Department of Biochemistry, Stanford University, CA 94305. Saffman E E EE Krasnow M A MA eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Antennapedia homeodomain protein 0 Chimeric Proteins 0 DNA-Binding Proteins 0 Proteins 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila IM abdA antp ubx Amino Acid Sequence Animal Base Sequence Chimeric Proteins genetics DNA Mutational Analysis DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Homeobox genetics Models, Genetic Molecular Sequence Data Promoter Regions (Genetics) genetics Proteins genetics Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0127022 20227084 10766017 2000 04 24 2000 04 24 2000 12 18

1420-682X 57 2 2000 Feb Determination of Drosophila photoreceptors: timing is everything. 195-214 This review covers recent findings concerning the specification of the photoreceptor subtypes in the Drosophila eye. Particular attention is paid to aspects of retinal patterning and differentiation where relative timing of events seems to be tightly controlled and essential for proper assembly of the compound eye. For example, specification of the founding photoreceptors of each cluster requires sequential positive and negative signaling through the Notch pathway, and reiterated signaling through the epidermal growth factor receptor leads to the pairwise recruitment of the distinct types of photoreceptors in discrete zones across the eye. Results suggest that different signaling environments for these two receptors may exist across the disc, and that receiving cells may constantly shift their predisposition to respond to such signals by adopting given fates. In addition, considerable data exist that the rate of expansion of retinal patterning across the disc is restricted to allow the orderly patterning of retinal precursors, and that one mechanism for controlling this rate may be the co-ordinated expression anterior to the furrow of factors which both inhibit and promote the expansion of retinal patterning. Finally, this review considers the possibility that the morphogenetic furrow serves as a moving source of morphogens which supply spatial information to both anterior and posterior tissue, providing temporal cues that regulate the many events involved in orderly assembly of the precise array of retinal cell types in the compound eye. Emory University School of Medicine, Department of Cell Biology, Atlanta, Georgia 30322-3030, USA. Brennan C A CA Moses K K eng Journal Article Review Review, Academic

SWITZERLAND Cell Mol Life Sci 9705402 0 Membrane Proteins 0 Transcription Factors 0 notch protein IM Animal Cell Differentiation Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Insect genetics physiology Membrane Proteins physiology Morphogenesis Photoreceptors, Invertebrate cytology embryology metabolism Signal Transduction Time Factors Transcription Factors physiology 170 FBrf0160738 22640860 12756168 2003 05 20 2003 09 10 2003 09 15

0950-1991 130 13 2003 Jul Notch activity in neural cells triggered by a mutant allele with altered glycosylation. 2829-40 The receptor protein Notch is inactive in neural precursor cells despite neighboring cells expressing ligands. We investigated specification of the R8 neural photoreceptor cells that initiate differentiation of each Drosophila ommatidium. The ligand Delta was required in R8 cells themselves, consistent with a lateral inhibitor function for Delta. By contrast, Delta expressed in cells adjacent to R8 could not activate Notch in R8 cells. The split mutation of Notch was found to activate signaling in R8 precursor cells, blocking differentiation and leading to altered development and neural cell death. split did not affect other, inductive functions of Notch. The Ile578-->Thr578 substitution responsible for the split mutation introduced a new site for O-fucosylation on EGF repeat 14 of the Notch extracellular domain. The O-fucose monosaccharide did not require extension by Fringe to confer the phenotype. Our results suggest functional differences between Notch in neural and non-neural cells. R8 precursor cells are protected from lateral inhibition by Delta. The protection is affected by modifications of a particular EGF repeat in the Notch extracellular domain. These results suggest that the pattern of neurogenesis is determined by blocking Notch signaling, as well as by activating Notch signaling. Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Li Yanxia Y Lei Liang L Irvine Kenneth D KD Baker Nicholas E NE Li Liang L eng R01-GM54594 GM NIGMS Journal Article

England Development 8701744 0 Membrane Proteins 0 delta protein 0 notch protein 3713-31-3 Fucose EC 2.4.- fringe protein EC 2.4.1.- N-Acetylglucosaminyltransferases IM Development. 2003 Aug;130(15):3587 Li Liang [corrected to Lei Liang] Animal Cell Line Drosophila melanogaster physiology Fucose metabolism Glycosylation Membrane Proteins genetics metabolism Mosaicism Mutation N-Acetylglucosaminyltransferases metabolism Neurons cytology physiology Phenotype Photoreceptors, Invertebrate cytology growth & development physiology Signal Transduction physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0040122 83221528 6407004 1983 07 08 1983 07 08 2000 12 18

0027-8424 80 10 1983 May Purine-resistant Drosophila melanogaster result from mutations in the adenine phosphoribosyltransferase structural gene. 2990-4 Mutants of Drosophila melanogaster selected for resistance to purine killing are deficient in adenine phosphoribosyltransferase (APRT; E.C. 2.4.2.7) activity. Genetic mapping and complementation analysis demonstrate that purine resistance, deficiency of APRT activity, and differences in the isoelectric point of APRT result from alterations at a single locus, Aprt (map position, 3:3.03). The level of APRT activity shows gene dose dependence in Aprt heterozygotes and in flies that are haploid for different Aprt alleles. Drosophila APRT is a dimer composed of apparently identical 23,000-dalton subunits. These results suggest that Aprt contains the structural gene for APRT. Johnson D H DH Friedman T B TB eng R01 AM26131 AM NIADDK Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Macromolecular Systems 0 Purines EC 2.4.2. Pentosyltransferases EC 2.4.2.7 Adenine Phosphoribosyltransferase IM Adenine Phosphoribosyltransferase genetics Animal Chromosome Mapping Drosophila melanogaster genetics Genes, Structural Isoelectric Point Macromolecular Systems Molecular Weight Mutation Pentosyltransferases genetics Purines toxicity Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0073598 95009505 7924981 1994 11 01 1994 11 01 2000 12 18

0950-1991 120 7 1994 Jul Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila. 1731-45 Loss-of-function mutations in Star impart a dominant rough eye phenotype and, when homozygous, are embryonic lethal with ventrolateral cuticular defects. We have cloned the Star gene and show that it encodes a novel protein with a putative transmembrane domain. Star transcript is expressed in a dynamic pattern in the embryo including in cells of the ventral midline. In the larval eye disc, Star is expressed first at the morphogenetic furrow, then in the developing R2, R5, and R8 cells as well as in the posterior clusters of the disc in additional R cells. Star interacts with Drosophila EGF receptor in the eye and mosaic analysis of Star in the larval eye disc reveals that homozygous Star patches contain no developing R cells. Taken together with the expression pattern at the morphogenetic furrow, these results demonstrate an early role for Star in photoreceptor development. Additionally, loss-of-function mutations in Star act as suppressors of R7 development in a sensitized genetic background involving the Son of sevenless (Sos) locus, and overexpression of Star enhances R7 development in this genetic background. Based on the genetic interactions with Sos, we suggest that Star also has a later role in photoreceptor development including the recruitment of the R7 cell through the sevenless pathway. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720. Kolodkin A L AL Pickup A T AT Lin D M DM Goodman C S CS Banerjee U U eng GENBANK L31886 1 R01 EY08152-01A1 EY NEI Journal Article

ENGLAND Development 8701744 0 Eye Proteins 0 Membrane Glycoproteins 0 Receptors, Cell Surface 0 sevenless protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Amino Acid Sequence Animal Base Sequence Drosophila melanogaster embryology genetics Embryonic Induction genetics Eye ultrastructure Eye Proteins genetics Genes, Insect genetics Genotype Membrane Glycoproteins genetics Molecular Sequence Data Phenotype Photoreceptors, Invertebrate embryology Receptor, Epidermal Growth Factor genetics Receptors, Cell Surface genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0044139 86165354 3007240 1986 04 25 1986 04 25 2000 12 18

0012-1606 114 1 1986 Mar Genetic and molecular analysis of fs(1)h, a maternal effect homeotic gene in Drosophila. 161-9 Mutations at the Drosophila melanogaster locus female sterile (1) homeotic (fs(1)h) result in segmental abnormalities including missing organs and homeotic transformations in the progeny of mutant mothers. Homeotic transformations are enhanced when the zygotes carry one of several third chromosome mutations, specifically alleles or deficiencies of the trithorax (trx) locus, also called Regulator-of-bithorax, and some alleles of bithorax complex (BX-C) genes. These observations suggest that maternally derived fs(1)h+ product is required, in interaction with trx and BX-C genes, for normal segment specification. The fs(1)h gene and an adjacent gene, lethal (1) myospheroid (l(1)mys), have been cloned by chromosomal walking. Mutations of fs(1)h were found within a 13-kb stretch of DNA. Poly(A)+ RNAs migrating as a doublet at 7.6 kb and a single band at 5.9 kb, which are homologous to the fs(1)h+ chromosomal region, are found in ovaries and early embryos. The largest RNAs are derived from a 20-kb chromosomal region encompassing the sites of all mapped fs(1)h alleles. Digan M E ME Haynes S R SR Mozer B A BA Dawid I B IB Forquignon F F Gans M M eng Journal Article

UNITED STATES Dev Biol 0372762 0 Mutagens EC 3.1.21 DNA Restriction Enzymes IM Alleles Animal Chromosome Mapping DNA Restriction Enzymes Drosophila melanogaster genetics Female Genes, Lethal Genotype Male Mutagens Mutation Phenotype Support, U.S. Gov't, P.H.S. X Chromosome FBrf0053739 91330446 1907895 1991 09 17 1991 09 17 2000 12 18

0192-253X 12 3 1991 Lethal(1) aberrant immune response mutations leading to melanotic tumor formation in Drosophila melanogaster. 173-87 Using P element-mediated mutagenesis we have isolated 20 X-linked lethal mutations, representing at least 14 complementation groups, which exhibit melanotic tumor phenotypes. We present the systematic analysis of this interesting group of lethal mutations that were selected for their visible melanotic or immune response. The lethal and melanotic tumor phenotypes of each lethal(1) aberrant immune response (air) mutation are pleiotropic effects of single genetic lesions. Lethality occurs throughout the larval and early pupal periods of development and larval development is extended in some air mutants. The air mutant lethal syndromes include abnormalities associated with the brain, haematopoietic organs, gut, salivary glands, ring glands, and imaginal discs. Additional characterization of the melanotic tumor mutations Tuml and tu(1)Szts have indicated that the melanotic tumor phenotype is similar to that observed in the air mutants. These studies have led to the proposal that two distinct classes of melanotic tumor mutations exist. Class 1 includes mutants in which melanotic tumors result from "autoimmune responses" or the response of an apparently normal immune system to the presence of abnormal target tissues. The Class 2 mutants display obvious defects in the haematopoietic organs or haemocytes, manifested as overgrowth, and the resulting aberrant immune system behavior may contribute to melanotic tumor formation. Developmental Biology Center, University of California, Irvine 92717. Watson K L KL Johnson T K TK Denell R E RE eng Journal Article

UNITED STATES Dev Genet 7909963 IM Animal Chromosome Mapping Drosophila melanogaster genetics Genes, Lethal Genetic Complementation Test Mutagenesis, Insertional Mutation Phenotype Support, Non-U.S. Gov't X Chromosome FBrf0064642 94063488 8244012 1994 01 06 1994 01 06 2000 12 18

0016-6731 135 2 1993 Oct The pleiotropic function of Delta during postembryonic development of Drosophila melanogaster. 527-39 Analysis of the development of Delta (Dl) temperature-sensitive mutants pulsed at restrictive temperature during larval and pupal stages reveals multiple phenocritical periods during which reduction of Dl function affects viability and development of adult structures. Dl function is required during the third larval instar for post-pupal viability and during the first day of pupal development for viability through eclosion. Dl function is required biphasically for the development of sensory bristles. Earlier pulses lead to bristle multiplication and later pulses lead to bristle loss. The exact intervals during which multiplication and loss are induced vary for different bristles. Dl function is also required for development of most, if not all, cell types in the retina. Different pulses result in reduction in eye size, scarring, and glossiness, as well as multiplication and loss of interommatidial bristles. We also define intervals during which Dl function is required for aspects of leg and wing development. Phenocritical periods for Dl function are temporally coincident with those previously reported for Notch (N), consistent with the hypothesis that the proteins encoded by Dl and N interact throughout development to assure correct specification of cell fates in a variety of imaginal tissues. Department of Biology, Indiana University, Bloomington 47405. Parody T R TR Muskavitch M A MA eng GM33291 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Aging genetics Alleles Animal Drosophila melanogaster genetics growth & development Eye anatomy & histology growth & development ultrastructure Genotype Larva Microscopy, Electron, Scanning Phenotype Pupa Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Temperature FBrf0043252 85295521 3929021 1985 10 15 1985 10 15 2002 01 17

0026-8925 200 2 1985 Recessive lethal mutations within the bithorax-complex in Drosophila. 335-42 Genetic deficiencies of the bithorax-complex (BX-C) in Drosophila, have been used to recover recessive lethal mutations in this chromosome region following mutagenesis. Complementation analysis separates these lethal mutations into five groups within a smaller deficiency, thought to remove the entire BX-C, and into 20 to the left and 4 to the right of the region. Homozygotes for each of only three groups of lethals, Ubx, abdA and AbdB, produce homoeotic segmental transformations in embryos. The functional domains of abdA and AbdB have been defined by changes in the appearance of larval hypodermal structures and of clones in imaginal tissue. The function abdA is required in all the compartments caudal to the anteroposterior border of abdominal segment 1 up to and including the anterior region of abdominal segment 8, whilst AbdB is required in abdominal segments 5 to 9. One allele of AbdB produces a ninth abdominal setal band and structures characteristic of head segments posterior to A8. Rare adult survivors hemizygous for an AbdB allele have eight abdominal segments in both sexes, and lack genitalia in females. Our findings are discussed in the context of the organisation of genetic functions within the BX-C. Tiong S S Bone L M LM Whittle J R JR eng Journal Article

GERMANY, WEST Mol Gen Genet 0125036 62-50-0 Ethyl Methanesulfonate IM Animal Chromosome Aberrations Chromosome Deletion Chromosome Disorders Drosophila melanogaster anatomy & histology drug effects genetics radiation effects Ethyl Methanesulfonate pharmacology Female Genes, Lethal Genes, Recessive Genetic Complementation Test Homozygote Male Mutation Support, Non-U.S. Gov't Thorax anatomy & histology FBrf0158927 22535684 12648473 2003 03 21 2003 05 07

0014-4827 284 1 2003 Mar 10 Signaling by the Drosophila epidermal growth factor receptor pathway during development. 140-9 In 1997 we wrote a review entitled "A thousand and one roles for the Drosophila epidermal growth factor (EGF) receptor (DER/EGFR)." We are not there yet in terms of the number of developmental roles assigned to this receptor in Drosophila. Nevertheless, DER has certainly emerged as one of the key players in development, since it is used repeatedly to direct cell fate choices, cell division, cell survival, and migration. A battery of activating ligands and an inhibitory ligand achieves this versatility. For the ligands that are produced as membrane-bound precursors, trafficking and processing are the key regulatory steps, determining the eventual temporal and spatial pattern of receptor activation. In most cases DER is activated at a short range, in the cells adjacent to the ones producing the active ligand. This activation dictates a binary choice. In some instances DER is also activated over a longer range, and multiple cell fate choices may be induced, according to its level of activation. A battery of negative feedback loops assures the limited range of DER induction. The distinct responses to DER activation in the different tissues depend upon combinatorial interactions with other signaling pathways and tissue-specific factors, at the level of target-gene regulation. Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot, Israel. benny.shilo@weizmann.ac.il Shilo Ben Zion BZ eng Journal Article Review Review, Tutorial

United States Exp Cell Res 0373226 0 Drosophila Proteins 0 Ligands 62229-50-9 Epidermal Growth Factor EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Drosophila Proteins physiology Drosophila melanogaster embryology growth & development Epidermal Growth Factor metabolism Feedback, Biochemical physiology Ligands Receptor, Epidermal Growth Factor physiology Signal Transduction physiology 103 FBrf0092847 97199427 9162472 1997 05 29 1997 05 29 2002 11 20

0960-9822 7 3 1997 Mar 1 Drosophila development: a receptor for ommatidial recruitment. R132-5 Recent work shows that the differentiation of all the cell types found in the compound eye of Drosophila melanogaster is induced by reiterative activation of the EGF receptor. Institut für Entwicklungsbiologie, Universität zu Köln, 50923 Köln, Germany. Klämbt C C eng Comment Journal Article

ENGLAND Curr Biol 9107782 0 Eye Proteins 0 Membrane Glycoproteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 bride of sevenless protein 0 sevenless protein 147954-53-8 gil protein 148175-53-5 spitz protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Curr Biol. 1997 Mar 1;7(3):166-75 9395407 Animal Cell Lineage Drosophila melanogaster embryology genetics Embryonic Induction Eye cytology embryology Eye Proteins genetics physiology Gene Expression Regulation, Developmental Membrane Glycoproteins genetics physiology Membrane Proteins genetics physiology Models, Biological Morphogenesis genetics Nerve Tissue Proteins genetics physiology Photoreceptors, Invertebrate physiology Receptor, Epidermal Growth Factor genetics physiology FBrf0053371 91330293 1907889 1991 09 18 1991 09 18 2000 12 18

0092-8674 66 3 1991 Aug 9 Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila. 433-49 Oogenesis in Drosophila involves specification of both germ cells and the surrounding somatic follicle cells, as well as the determination of oocyte polarity. We found that two neurogenic genes, Notch and Delta, are required in oogenesis. These genes encode membrane proteins with epidermal growth factor repeats and are essential in the decision of an embryonic ectodermal cell to take on the fate of neuroblast or epidermoblast. In oogenesis, mutation in either gene leads to an excess of posterior follicle cells, a cell fate change reminiscent of the hyperplasia of neuroblasts seen in neurogenic mutant embryos. Furthermore, the Notch mutation in somatic cells causes mislocalization of bicoid in the oocyte. These results suggest that the neurogenic genes Notch and Delta are involved in both follicle cell development and the establishment of anterior-posterior polarity in the oocyte. Howard Hughes Medical Institute, University of California, San Francisco 94143-0724. Ruohola H H Bremer K A KA Baker D D Swedlow J R JR Jan L Y LY Jan Y N YN eng Journal Article

UNITED STATES Cell 0413066 0 RNA, Messenger IM Dl N bcd bib neu Animal Cell Communication Cell Compartmentation Drosophila melanogaster embryology genetics Female Mutation Nervous System embryology Nucleic Acid Hybridization Oocytes cytology physiology Oogenesis Ovary cytology RNA, Messenger metabolism Support, Non-U.S. Gov't FBrf0090744 96428599 8831701 1996 11 07 1996 11 07 2000 12 18

0006-291X 226 3 1996 Sep 24 Insulin acts as an embryonic growth factor for Drosophila neural cells. 855-61 The isolation of the Drosophila insulin receptor gene and the recent analysis of loss of function mutants have clearly implicated insulin signalling in embryonic nervous system development. Here we study the presence of insulin in the embryo and we characterize the cellular processes affected by insulin in embryonic neural cells. We find that 7.5% of the cells in the 15-18 h Drosophila embryo contain insulin immunoreactivity by flow cytometry. In the embryonic-derived cell line Schneider 1, we show that human insulin is capable of stimulating proliferation and neural differentiation. Thus, the action of insulin on the developing Drosophila nervous system appears to be as pleiotropic as in vertebrates. Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain. Pimentel B B de la Rosa E J EJ de Pablo F F eng Journal Article

UNITED STATES Biochem Biophys Res Commun 0372516 0 Growth Substances 0 Recombinant Proteins 11061-68-0 Insulin IM Animal Cell Differentiation drug effects Cell Division drug effects Cell Line Drosophila melanogaster embryology Embryo, Nonmammalian physiology Growth Substances analysis pharmacology physiology Human Insulin analysis pharmacology physiology Neurons cytology drug effects physiology Recombinant Proteins pharmacology Signal Transduction Support, Non-U.S. Gov't FBrf0055071 92022569 1925579 1991 11 01 1991 11 01 2000 12 18

0036-8075 254 5029 1991 Oct 11 Toward cloning and mapping the genome of Drosophila. 221-5 An ultimate goal of Drosophila genetics is to identify and define the functions of all the genes in the organism. Traditional approaches based on the isolation of mutant genes have been extraordinary fruitful. Recent advances in the manipulation and analysis of large DNA fragments have made it possible to develop detailed molecular maps of the Drosophila genome as the initial steps in determining the complete DNA sequence. Department of Biology, University of California, Los Angeles 90024. Merriam J J Ashburner M M Hartl D L DL Kafatos F C FC eng Journal Article Review Review, Tutorial

UNITED STATES Science 0404511 IM Animal Base Sequence Chromosome Mapping Chromosomes Cloning, Molecular Drosophila melanogaster genetics Evolution Gene Rearrangement Genes Genome Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 56 FBrf0129769 20419844 10961941 2000 12 18 2001 02 15

0300-5127 28 4 2000 Exploring the Caenorhabditis elegans and Drosophila melanogaster genomes to understand neuropeptide and peptidase function. 464-9 Comparison of peptidase gene families in the newly released Drosophila melanogaster and Caenorhabditis elegans genomes highlights important differences in peptidase distributions with relevance to the evolution of both form and function in these two organisms and can help to identify the most appropriate model when using comparative studies relevant to the human condition. School of Biology, University of Leeds, Leeds LS2 9JT, U.K. d.coates@leeds.ac.uk Coates D D Siviter R R Isaac R E RE eng Journal Article Review Review, Tutorial

ENGLAND Biochem Soc Trans 7506897 0 Neuropeptides 7440-66-6 Zinc EC 3.4 Peptide Hydrolases EC 3.4.15.1 Peptidyl-Dipeptidase A EC 3.4.21 Serine Endopeptidases EC 3.4.24 Metalloendopeptidases EC 3.4.24.- Matrix Metalloproteinases EC 3.4.24.11 Neprilysin IM Animal Caenorhabditis elegans genetics Drosophila melanogaster genetics Genome Invertebrates Matrix Metalloproteinases genetics Metalloendopeptidases genetics Neprilysin genetics Neuropeptides genetics physiology Peptide Hydrolases genetics physiology Peptidyl-Dipeptidase A genetics Phenotype Phylogeny Serine Endopeptidases genetics Support, Non-U.S. Gov't Zinc metabolism 16 FBrf0151232 22105504 12111533 2002 07 11 2003 01 13

0302-766X 309 1 2002 Jul Clock mechanisms in Drosophila. 11-26 Mechanisms underlying circadian clock function in Drosophila melanogaster have been revealed by genetic and molecular approaches. Two interlocked transcriptional feedback loops involving at least the period, timeless, Clock,and cycle genes generate molecular oscillations that are believed to control behavioral rhythmicity and other clock outputs. These oscillations are further enhanced and fine-tuned to match the duration of the solar day by post-transcriptional and post-translational mechanisms depending on the PERIOD and TIMELESS proteins and on the protein kinases DOUBLE-TIME and SHAGGY. Light is the principal zeitgeber for synchronizing molecular and behavioral rhythmicity via the blue-light photoreceptor CRYPTOCHROME and the TIMELESS protein. In addition, light seems required for maintaining robust molecular oscillations at least in peripheral clock-gene-expressing tissues like the eyes, antennae, or Malpighian tubules. Relaying temporal information to cells and tissues expressing overt biological rhythms involves regulation of "output genes" at multiple levels. Although their regulation depends on the major clock genes, the majority of the clock-controlled genes are not direct targets of clock factors. Universität Regensburg, Institut für Zoologie, Lehrstuhl für Entwicklungsbiologie, Universitätsstrasse 31, 93040 Regensburg, Germany. ralf.stanewsky@biologie.uni-regensburg.de Stanewsky Ralf R eng Journal Article Review Review Literature 2002 05 29

Germany Cell Tissue Res 0417625 IM Animal Biological Clocks physiology Drosophila physiology Support, Non-U.S. Gov't 126 FBrf0101998 98190322 9529525 1998 04 23 1998 04 23 2002 11 01

0026-8925 257 4 1998 Feb A genetic screen for elements of the network that regulates neurogenesis in Drosophila. 442-51 The development of external sensory organs on the notum of Drosophila is promoted by the proneural genes achaete and scute. Their activity defines proneural cell clusters in the wing imaginal disc. Ectopic expression, under control of the GAL4 system, of the proneural gene lethal of scute (l'sc) causes the development of ectopic bristles. Persistent ectopic expression of l'sc is not sufficient to impose a neural fate on any given cell. This implies that mutual inhibition, mediated by the Notch signaling pathway, occurs among the cells of the ectopic proneural cluster. Consequently, the dominant, quantifiable phenotype associated with ectopic expression of l'sc is modified by mutations in genes known to be involved in neurogenesis. This phenotype has been utilized to screen for dominant enhancers and suppressors that modify the number of ectopic bristles. In this way, about 100,000 progeny of EMS or X-ray-treated flies have been analyzed to identify autosomal genes involved in regulation of the neural fate. In addition 1200 chromosomes carrying lethal P-element insertions were screened for modifiers. Besides mutations in genes expected to modify the phenotype, we have isolated mutations in six genes not known so far to be involved in neurogenesis. Institut für Entwicklungsbiologie, Universität zu Köln, Germany. Röttgen G G Wagner T T Hinz U U eng Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA Transposable Elements 0 GAL4 protein, S cerevisiae 0 Insect Proteins 0 Recombinant Fusion Proteins 0 Transcription Factors 0 lethal of scute protein, Drosophila IM Alleles Animal Chromosome Mapping DNA Transposable Elements Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Female Gene Expression Regulation, Developmental Genes, Dominant Genetic Complementation Test Insect Proteins biosynthesis genetics physiology Male Mechanoreceptors metabolism Mutagenesis Phenotype Recombinant Fusion Proteins physiology Sense Organs embryology Support, Non-U.S. Gov't Transcription Factors biosynthesis genetics physiology FBrf0059044 93204998 8384310 1993 04 20 1993 04 20 2002 11 01

0270-7306 13 4 1993 Apr Mutations in the Drosophila gene encoding ribosomal protein S6 cause tissue overgrowth. 2524-35 We have characterized two P-element-induced, lethal mutations in Drosophila melanogaster which affect the larval hemocytes, mediators of the insect immune response. Each mutant displays larval melanotic tumors characteristic of mutations affecting the insect cellular immune system, and the moribund animals develop grossly hypertrophied hematopoietic organs because of increased cell proliferation and extra rounds of endoreduplication in some hematopoietic cells. Surprisingly, these mutations are due to P element insertions in the 5' regulatory region of the Drosophila gene encoding ribosomal protein S6 and cause a reduction of S6 transcript abundance in mutant larvae. Center for Basic Cancer Research, Kansas State University, Manhattan 66506. Stewart M J MJ Denell R R eng GENBANK L0274 L0275 L0276 Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA Transposable Elements 0 Oligodeoxyribonucleotides 0 RNA, Messenger 0 Ribosomal Protein S6 0 Ribosomal Proteins IM S6 bys ct sn Animal Base Sequence Chromosome Mapping Cloning, Molecular Comparative Study DNA Transposable Elements Drosophila melanogaster cytology genetics Gene Expression Gene Expression Regulation Genes, Lethal Genes, Structural, Insect Hematopoietic Stem Cells physiology Human In Situ Hybridization Molecular Sequence Data Mutagenesis, Insertional Mutation Oligodeoxyribonucleotides chemistry RNA, Messenger genetics Rats Restriction Mapping Ribosomal Protein S6 Ribosomal Proteins genetics Sequence Alignment Support, Non-U.S. Gov't X Chromosome FBrf0080088 95229064 7713435 1995 05 18 1995 05 18 2003 06 16

0016-6731 139 2 1995 Feb Cis and trans interactions between the iab regulatory regions and abdominal-A and abdominal-B in Drosophila melanogaster. 835-48 The infra-abdominal (iab) elements in the bithorax complex of Drosophila melanogaster regulate the transcription of the homeotic genes abdominal-A (abd-A) and Abdominal-B (Abd-B) in cis. Here we describe two unusual aspects of regulation by the iab elements, revealed by an analysis of an unexpected complementation between mutations in the Abd-B transcription unit and these regulatory regions. First, we find that iab-6 and iab-7 can regulate Abd-B in trans. This iab trans regulation is insensitive to chromosomal rearrangements that disrupt transvection effects at the nearby Ubx locus. In addition, we show that a transposed Abd-B transcription unit and promoter on the Y chromosome can be activated by iab elements located on the third chromosome. These results suggest that the iab regions can regulate their target promoter located at a distant site in the genome in a manner that is much less dependent on homologue pairing than other transvection effects. The iab regulatory regions may have a very strong affinity for the target promoter, allowing them to interact with each other despite the inhibitory effects of chromosomal rearrangements. Second, by generating abd-A mutations on rearrangement chromosomes that break in the iab-7 region, we show that these breaks induce the iab elements to switch their target promoter from Abd-B to abd-A. These two unusual aspects of iab regulation are related by the iab-7 breakpoint chromosomes that prevent iab elements from acting on Abd-B and allow them to act on abd-A. We propose that the iab-7 breaks prevent both iab trans regulation and target specificity by disrupting a mechanism that targets the iab regions to the Abd-B promoter. Department of Human Genetics, Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112, USA. Hendrickson J E JE Sakonju S S eng Journal Article

UNITED STATES Genetics 0374636 0 Abd-B proteins, Drosophila 0 DNA-Binding Proteins 0 Insect Hormones 0 Proteins 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila IM Abd-B Ubx abd-A Animal DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) genetics Female Gene Expression Regulation, Developmental genetics Gene Rearrangement Genes, Homeobox genetics Genes, Insect genetics Genetic Complementation Test Insect Hormones genetics Male Mutation physiology Promoter Regions (Genetics) genetics Proteins genetics Regulatory Sequences, Nucleic Acid genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Thorax growth & development Translocation (Genetics) Y Chromosome FBrf0064691 94063483 8244007 1994 01 06 1994 01 06 2002 11 01

0016-6731 135 2 1993 Oct Genetic dissection of pointed, a Drosophila gene encoding two ETS-related proteins. 455-68 The Drosophila gene pointed (pnt) is required for the differentiation of a number of tissues during embryogenesis, including the ventral ectoderm, the nervous system, the tracheal system and certain muscle fibers. The phenotypes associated with strong pointed alleles are reflected by a complex pointed expression pattern during embryogenesis. Two promoters, P1 and P2, separated by some 50 kb of genomic sequences, direct the transcription of two different transcript forms, encoding two different proteins related to the ETS family of transcription factors. To assess the individual functions of the two different pointed protein forms, we have generated new pointed alleles affecting either the P1 or the P2 transcript, termed P1 and P2 alleles, respectively. Genetic analysis reveals partial heteroallelic complementation between certain pointed P1 and P2 alleles. Surviving trans-heterozygous flies have rough eyes, abnormal wings and halters, suggesting a requirement for pointed function during their imaginal disc development. Further genetic analysis demonstrates that expression of a given pointed P2 allele depends on trans-acting transcriptional regulatory sequences. We have identified two chromosomal domains with opposite regulatory effects on the transcriptional activity of the pointed P2 promoter, one trans-activates and the other trans-represses pointed P2 expression. By deletion mapping we were able to localize these control regions within the 5' region of the pointed P2 transcript. Institut für Entwicklungsbiologie, Universität zu Köln, Germany. Scholz H H Deatrick J J Klaes A A Klämbt C C eng Journal Article

UNITED STATES Genetics 0374636 0 Proto-Oncogene Proteins 0 pointed protein 0 proto-oncogene protein ets 9007-49-2 DNA IM pnt Alleles Animal DNA analysis Drosophila melanogaster anatomy & histology embryology genetics Ectoderm physiology Embryo and Fetal Development genetics Embryo, Nonmammalian physiology Enhancer Elements (Genetics) Exons Gene Deletion Genetic Complementation Test Homozygote Muscles embryology Mutagenesis, Insertional Nervous System embryology Phenotype Proto-Oncogene Proteins genetics Support, Non-U.S. Gov't FBrf0123221 20076861 10607562 2000 02 10 2000 02 10 2000 12 18

0960-9822 9 23 1999 Dec 2 Drosophila wing melanin patterns form by vein-dependent elaboration of enzymatic prepatterns. 1382-91 BACKGROUND: Animal melanin patterns are involved in diverse aspects of their ecology, from thermoregulation to mimicry. Many theoretical models have simulated pigment patterning, but little is known about the developmental mechanisms of color pattern formation. In Drosophila melanogaster, several genes are known to be necessary for cuticular melanization, but the involvement of these genes in melanin pattern evolution is unknown. We have taken a genetic approach to elucidate the developmental mechanisms underlying melanin pattern formation in various drosophilids. RESULTS: We show that, in D. melanogaster, tyrosine hydroxylase (TH) and dopa decarboxylase (DDC) are required for melanin synthesis. Ectopic expression of TH, but not DDC, alone was sufficient to cause ectopic melanin patterns in the wing. Thus, changes in the level of expression of a single gene can result in a new level of melanization. The ontogeny of this ectopic melanization resembled that found in Drosophila species bearing wing melanin patterns and in D. melanogaster ebony mutants. Importantly, we discovered that in D. melanogaster and three other Drosophila species these wing melanin patterns are dependent upon and shaped by the circulation patterns of hemolymph in the wing veins. CONCLUSIONS: Complex wing melanin patterns are determined by two distinct developmental mechanisms. Spatial prepatterns of enzymatic activity are established late in wing development. Then, in newly eclosed adults, melanin precursors gradually diffuse out from wing veins and are oxidized into dark brown or black melanin. Both the prepatterning and hemolymph-supplied components of this system can change during evolution to produce color pattern diversity. Laboratory of Molecular Biology, Howard Hughes Medical Institute, University of Wisconsin, Madison 53706, USA. True J R JR Edwards K A KA Yamamoto D D Carroll S B SB eng Journal Article

ENGLAND Curr Biol 9107782 0 DNA-Binding Proteins 0 Insect Proteins 0 Melanins 0 ebony protein 51-61-6 Dopamine EC 1.14.16.2 Tyrosine 3-Monooxygenase EC 4.1.1.- Dopa Decarboxylase IM Animal Body Patterning drug effects Comparative Study DNA-Binding Proteins genetics Dopa Decarboxylase biosynthesis genetics physiology Dopamine pharmacology Drosophila anatomy & histology enzymology metabolism Evolution Female Gene Expression Insect Proteins genetics Male Melanins biosynthesis Mutation Phenotype Species Specificity Support, Non-U.S. Gov't Tyrosine 3-Monooxygenase biosynthesis genetics physiology Veins anatomy & histology metabolism Wing blood supply enzymology metabolism FBrf0051931 91032923 2121595 1990 12 05 1990 12 05 2000 12 18

0016-6731 126 1 1990 Sep Transvection in the Drosophila Ultrabithorax gene: a Cbx1 mutant allele induces ectopic expression of a normal allele in trans. 177-84 In wild-type Drosophila melanogaster larvae, the Ultrabithorax (Ubx) gene is expressed in the haltere imaginal discs but not in the majority of cells of the wing imaginal discs. Ectopic expression of the Ubx gene in wing discs can be elicited by the presence of Contrabithorax (Cbx) gain-of-function alleles of the Ubx gene or by loss-of-function mutations in Polycomb (Pc) or in other trans-regulatory genes which behave as repressors of Ubx gene activity. Several Ubx loss-of-function alleles cause the absence of detectable Ubx proteins (UBX) or the presence of truncated UBX lacking the homeodomain. We have compared adult wing phenotypes with larval wing disc UBX patterns in genotypes involving double mutant chromosomes carrying in cis one of those Ubx mutations and the Cbx1 mutation. We show that such double mutant genes are (1) active in the same cells in which the single mutant Cbx1 is expressed, although they are unable to yield functional proteins, and (2) able to induce ectopic expression of a normal homologous Ubx allele in a part of the cells in which the single mutant Cbx1 is active. That induction is conditional upon pairing of the homologous chromosomes (the phenomenon known as transvection), and it is not mediated by UBX. Depletion of Pc gene products by Pc3 mutation strongly enhances the induction phenomenon, as shown by (1) the increase of the number of wing disc cells in which induction of the homologous allele is detectable, and (2) the induction of not only a paired normal allele but also an unpaired one. Centro de Biología Molecular, C.S.I.C., Universidad Autónoma de Madrid, Spain. Castelli-Gair J E JE Micol J L JL García-Bellido A A eng Journal Article

UNITED STATES Genetics 0374636 IM Cbx Ubx Alleles Animal Drosophila melanogaster anatomy & histology genetics Gene Expression Regulation Genes Genotype Morphogenesis Mutation Phenotype Support, Non-U.S. Gov't FBrf0091028 97158721 9006081 1997 02 24 1997 02 24 2000 12 18

0950-1991 124 1 1997 Jan Compartmental organization of the Drosophila genital imaginal discs. 205-18 We have investigated the anterior and posterior compartmental organization of the genital imaginal disc. Unlike the thoracic discs, the genital disc is a compound disc consisting of three primordia--the female genital, male genital, and anal primordia. Here we provide evidence that each primordium is divided into anterior and posterior compartments. Genes that are known to be expressed in compartment-specific manners in other discs (engrailed, hedgehog, patched, decapentaplegic, wingless and cubitus interruptus) are expressed in analogous patterns in each primordium of the genital disc. Specifically, engrailed and cubitus interruptus are expressed in complementary domains, while patched, decapentaplegic and wingless are expressed along the border between the two domains. Mitotic clones induced at the beginning of the second larval instar do not cross the boundary between the engrailed-expressing and cubitus interruptus-expressing domains, indicating that these domains are true genetic compartments. Furthermore, we examined the phenotypes of mutant clones of the cAMP-dependent protein kinase A and engrailed-invected, genes that are known to play compartment-specific functions in other discs. These experiments demonstrate that the anterior/posterior patterning functions of these genes are conserved in the genital disc. The adult clonal phenotypes of protein kinase A and engrailed-invected mutants also provide a more detailed map of the adult genitalia and analia with respect to the anterior/posterior compartmental subdivision. Our results lead us to propose a new model to describe the anterior and posterior compartmental organization of the genital disc. Department of Developmental Biology, Stanford University, CA 94305, USA. Chen E H EH Baker B S BS eng Journal Article

ENGLAND Development 8701744 EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Cyclic AMP-Dependent Protein Kinases genetics metabolism Drosophila melanogaster embryology growth & development physiology Embryo, Nonmammalian cytology physiology Embryonic Induction Female Gene Expression Regulation, Developmental Genes, Insect Genitalia cytology embryology growth & development Male Microscopy, Confocal Mitosis Mutation Sex Differentiation Support, U.S. Gov't, P.H.S. FBrf0051826 91007264 1976570 1990 11 19 1990 11 19 2000 12 18

0890-9369 4 7 1990 Jul Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity. 1209-23 We characterized a gene, extradenticle, which seems to interact with a specific subset of Drosophila homeo domain proteins, possibly affecting their target specificity. This interpretation is based on an examination of the zygotic and maternal effect phenotypes of extradenticle mutations. In embryos with reduced levels of extradenticle gene product, anterior and posterior segmental transformations occur. Segmental identity in Drosophila is mediated by the products of the Antennapedia and bithorax complexes. These homeo domain proteins are thought to regulate different target genes specifically in each segment, resulting in different morphologies. extradenticle alters segmental identity without affecting the pattern of expression of homeotic genes. Genetic tests demonstrate that in extradenticle mutants, the homeotic proteins are functional and act in their normal segmental domains, yet segmental identities are altered. Even when homeotic proteins are ectopically expressed under the control of a heterologous promoter, extradenticle mutations affect their consequences. Thus, in the absence of sufficient extradenticle product, altered segmental morphology results from alteration of the functional consequences of specific homeo domain proteins, possibly through alterations in their target gene specificity. extradenticle is also expressed maternally. Complete removal of extradenticle, maternally and zygotically, leads to specific alterations in segmentation, many of which result from failure to maintain the expression of the homeo domain protein engrailed. Department of Biology, Princeton University, New Jersey 08544-1003. Peifer M M Wieschaus E E eng 5R01HD22780 HD NICHD Journal Article

UNITED STATES Genes Dev 8711660 0 DNA-Binding Proteins 0 Recombinant Fusion Proteins 0 Transcription Factors IM Animal DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Gene Expression Regulation Genes, Homeobox Genes, Regulator Morphogenesis Promoter Regions (Genetics) Recombinant Fusion Proteins pharmacology Support, U.S. Gov't, P.H.S. Transcription Factors genetics FBrf0148960 22010046 12015286 2002 05 16 2002 07 22 2002 11 01

0950-1991 129 11 2002 Jun Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. 2565-76 The secreted glycoprotein Wingless (Wg) acts through a conserved signaling pathway to regulate target gene expression. Wg signaling causes nuclear translocation of Armadillo, the fly beta-catenin, which then complexes with the DNA-binding protein TCF, enabling it to activate transcription. Though many nuclear factors have been implicated in modulating TCF/Armadillo activity, their importance remains poorly understood. This work describes a ubiquitously expressed protein, called Pygopus, which is required for Wg signaling throughout Drosophila development. Pygopus contains a PHD finger at its C terminus, a motif often found in chromatin remodeling factors. Overexpression of pygopus also blocks the pathway, consistent with the protein acting in a complex. The pygopus mutant phenotype is highly, though not exclusively, specific for Wg signaling. Epistasis experiments indicate that Pygopus acts downstream of Armadillo nuclear import, consistent with the nuclear location of heterologously expressed protein. Our data argue strongly that Pygopus is a new core component of the Wg signaling pathway that acts downstream or at the level of TCF. Department of Molecular, Cellular and Developmental Biology, University of Michigan, Natural Science Building, Ann Arbor 48109, USA. Parker David S DS Jemison Jemileh J Cadigan Kenneth M KM eng R01 GM59846 GM NIGMS Journal Article

England Development 8701744 0 Carrier Proteins 0 Drosophila Proteins 0 High Mobility Group Proteins 0 Insect Proteins 0 Luminescent Proteins 0 Nuclear Proteins 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 T cell factor, insect 0 armadillo protein, Drosophila 0 pygopus protein, Drosophila 117758-26-6 wingless protein, Drosophila 147336-22-9 green fluorescent protein IM Animal Animals, Genetically Modified Carrier Proteins genetics Cell Nucleus physiology Cells, Cultured Drosophila Proteins genetics Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental High Mobility Group Proteins metabolism Insect Proteins metabolism Luminescent Proteins genetics Nuclear Proteins metabolism Proto-Oncogene Proteins physiology Repressor Proteins metabolism physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection FBrf0155655 22378505 12490253 2002 12 19 2003 03 05

0959-4388 12 6 2002 Dec Drugs, flies, and videotape: the effects of ethanol and cocaine on Drosophila locomotion. 639-45 Drosophila melanogaster has been introduced recently as a model organism in which to study the mechanisms by which drugs of abuse change behavior and by which the nervous system changes upon repeated drug exposure. Surprising similarities between flies and mammals have begun to emerge at the behavioral, neurochemical and molecular levels. Department of Anatomy, University of California at San Francisco, 513 Parnassus Avenue, 94143-0452, USA. adrianr@itsa.ucsf.edu Rothenfluh Adrian A Heberlein Ulrike U eng Journal Article Review Review, Tutorial

England Curr Opin Neurobiol 9111376 50-36-2 Cocaine 51-61-6 Dopamine 60-92-4 Cyclic AMP 64-17-5 Ethanol IM Animal Behavior, Animal drug effects Circadian Rhythm physiology Cocaine pharmacology Cyclic AMP metabolism Dopamine metabolism Drosophila melanogaster Drug Tolerance physiology Ethanol pharmacology Locomotion drug effects Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 58 FBrf0101896 98198839 9539432 1998 06 01 1998 06 01 2000 12 18

0016-6731 148 3 1998 Mar Genetic and developmental characterization of Dmca1D, a calcium channel alpha1 subunit gene in Drosophila melanogaster. 1159-69 To begin unraveling the functional significance of calcium channel diversity, we identified mutations in Dmca1D, a Drosophila calcium channel alpha1 subunit cDNA that we recently cloned. These mutations constitute the l(2)35Fa lethal locus, which we rename Dmca1D. A severe allele, Dmca1D(X10), truncates the channel after the IV-S4 transmembrane domain. These mutants die as late embryos because they lack vigorous hatching movements. In the weaker allele, Dmca1D(AR66), a cysteine in transmembrane domain I-S1 is changed to tyrosine. Dmca1D(AR66) embryos hatch but pharate adults have difficulty eclosing. Those that do eclose have difficulty in fluid-filling of the wings. These studies show that this member of the calcium channel alpha1 subunit gene family plays a nonredundant, vital role in larvae and adults. Department of Biochemical Pharmacology, The State University of New York at Buffalo, 14260-1200, USA. Eberl D F DF Ren D D Feng G G Lorenz L J LJ Van Vactor D D Hall L M LM eng HL39369 HL NHLBI Journal Article

UNITED STATES Genetics 0374636 0 Calcium Channels 0 Codon, Terminator 0 Cosmids 0 Dmca1D protein IM Alleles Animal Calcium Channels analysis genetics Chromosome Mapping Codon, Terminator Cosmids Drosophila melanogaster embryology genetics Genes, Insect Genes, Lethal Mutagenesis Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0134734 21103687 11162110 2001 02 22 2001 03 15

0022-2836 305 5 2001 Feb 2 Cadherin superfamily proteins in Caenorhabditis elegans and Drosophila melanogaster. 1011-24 The ability to form selective cell-cell adhesions is an essential property of metazoan cells. Members of the cadherin superfamily are important regulators of this process in both vertebrates and invertebrates. With the advent of genome sequencing projects, determination of the full repertoire of cadherins available to an organism is possible and here we present the identification and analysis of the cadherin repertoires in the genomes of Caenorhabditis elegans and Drosophila melanogaster. Hidden Markov models of cadherin domains were matched to the protein sequences obtained from the translation of the predicted gene sequences. Matches were made to 21 C. elegans and 18 D. melanogaster sequences. Experimental and theoretical work on C. elegans sequences, and data from ESTs, show that three pairs of genes, and two triplets, should be merged to form five single genes. It also produced sequence changes at one or both of the 5' and 3' termini of half the sequences. In D. melanogaster it is probable that two of the cadherin genes should also be merged together and that three cadherin genes should be merged with other neighbouring genes.Of the 15 cadherin proteins found in C. elegans, 13 have the features of cell surface proteins, signal sequences and transmembrane helices; the other two have only signal sequences. Of the 17 in D. melanogaster, 11 at present have both features and another five have transmembrane helices. The evidence currently available suggests about one-third of the cadherins in the two organisms can be grouped into subfamilies in which all, or parts of, the molecules are conserved. Each organism also has a approximately 980 residue protein (CDH-11 and CG11059) with two cadherin domains and whose sequences match well over their entire length two proteins from human brain. Two proteins in C. elegans, HMR-1A and HMR-1B, and three in D. melanogaster, CadN, Shg and CG7527, have cytoplasmic domains homologous to those of the classical cadherin genes of chordates but their extracellular regions have different domain structures. Other common subclasses include the seven-helix membrane cadherins, Fat-like protocadherins and the Ret-like cadherins. At present, the remaining cadherins have no obvious similarities in their extracellular domain architecture or homologies to their cytoplasmic domains and may, therefore, represent species-specific or phylum-specific molecules. MRC, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK. eeh@mrc-lmb.cam.ac.uk Hill E E Broadbent I D ID Chothia C C Pettitt J J eng Journal Article

England J Mol Biol 2985088R 0 Cadherins 0 Laminin 62229-50-9 Epidermal Growth Factor 7440-70-2 Calcium IM Amino Acid Sequence Animal Binding Sites Cadherins chemistry genetics metabolism Caenorhabditis elegans chemistry Calcium metabolism Comparative Study Computational Biology methods Conserved Sequence Drosophila melanogaster chemistry Epidermal Growth Factor chemistry Genomics Laminin chemistry Models, Molecular Molecular Sequence Data Multigene Family Protein Structure, Tertiary Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Support, Non-U.S. Gov't Vertebrates FBrf0083173 96120350 7498774 1996 01 17 1996 01 17 2000 12 18

0016-6731 140 4 1995 Aug A screen for modifiers of Deformed function in Drosophila. 1339-52 Proteins produced by the homeotic genes of the Hox family assign different identifies to cells on the anterior/posterior axis. Relatively little is known about the signalling pathways that modulate their activities or the factors with which they interact to assign specific segmental identifies. To identify genes that might encode such functions, we performed a screen for second site mutations that reduce the viability of animals carrying hypomorphic mutant alleles of the Drosophila homeotic locus, Deformed. Genes mapping to six complementation groups on the third chromosome were isolated as modifiers of Deformed function. Products of two of these genes, sallimus and moira, have been previously proposed as homeotic activators since they suppress the dominant adult phenotype of Polycomb mutants. Mutations in hedgehog, which encodes secreted signalling proteins, were also isolated as Deformed loss-of-function enhancers. Hedgehog mutant alleles also suppress the Polycomb phenotype. Mutations were also isolated in a few genes that interact with Deformed but not with Polycomb, indicating that the screen identified genes that are not general homeotic activators. Two of these genes, cap 'n' collar and defaced, have defects in embryonic head development that are similar to defects seen in loss of function Deformed mutants. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven Connecticut 06520-8114, USA. Harding K W KW Gellon G G McGinnis N N McGinnis W W eng GM-07499 GM NIGMS HD-30368 HD NICHD Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Dfd protein 0 Homeodomain Proteins 0 Proteins 0 trithorax gene product 134549-01-2 Polycomb protein, insect 149291-21-4 hedgehog protein, Drosophila IM Animal Chromosome Mapping Crosses, Genetic DNA-Binding Proteins genetics physiology Drosophila melanogaster embryology genetics Female Gene Expression Regulation, Developmental Genes, Dominant Genes, Lethal Genetic Complementation Test Head embryology Homeodomain Proteins genetics physiology Male Morphogenesis genetics Phenotype Proteins genetics physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic FBrf0129866 20370879 10908580 2000 08 18 2000 08 18 2003 06 16

0021-9525 150 2 2000 Jul 24 Regulated expression of nullo is required for the formation of distinct apical and basal adherens junctions in the Drosophila blastoderm. 391-401 During cellularization, the Drosophila embryo undergoes a large-scale cytokinetic event that packages thousands of syncytial nuclei into individual cells, resulting in the de novo formation of an epithelial monolayer in the cortex of the embryo. The formation of adherens junctions is one of the many aspects of epithelial polarity that is established during cellularization: at the onset of cellularization, the Drosophila beta-catenin homologue Armadillo (Arm) accumulates at the leading edge of the cleavage furrow, and later to the apicolateral region where the zonula adherens precursors are formed. In this paper, we show that the basal accumulation of Arm colocalizes with DE-cadherin and Dalpha-catenin, and corresponds to a region of tight membrane association, which we refer to as the basal junction. Although the two junctions are similar in components and function, they differ in their response to the novel cellularization protein Nullo. Nullo is present in the basal junction and is required for its formation at the onset of cellularization. In contrast, Nullo is degraded before apical junction formation, and prolonged expression of Nullo blocks the apical clustering of junctional components, leading to morphological defects in the developing embryo. These observations reveal differences in the formation of the apical and basal junctions, and offer insight into the role of Nullo in basal junction formation. Howard Hughes Medical Institute, Molecular Biology Department, Princeton University, Princeton, New Jersey 08540, USA. Hunter C C Wieschaus E E eng 5R37HD15587 HD NICHD Journal Article

UNITED STATES J Cell Biol 0375356 0 Insect Proteins 147883-16-7 nullo protein, Drosophila IM Animal Cell Adhesion genetics Cell Membrane metabolism ultrastructure Drosophila melanogaster Embryo, Nonmammalian embryology metabolism ultrastructure Embryonic Induction physiology Epithelial Attachment embryology metabolism ultrastructure Gene Expression Regulation, Developmental physiology Insect Proteins genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0046259 87248071 3110012 1987 07 24 1987 07 24 2000 12 18

0378-1119 51 2-3 1987 Sequence and genomic structure of ras homologues Dmras85D and Dmras64B of Drosophila melanogaster. 129-37 The ras homologues of Drosophila melanogaster located at 85D and 64B on the polytene chromosome map were cloned using the Ha-ras gene of Harvey murine sarcoma virus as a probe. The genomic sequences of Dmras85D and Dmras64B were determined and shown to differ from previously published sequences. Dmras85D is much more similar to the Ha-ras, Ki-ras, and N-ras genes than it is to either the Dmras64B gene or to the ras genes of Saccharomyces cerevisiae. Comparison of the Dmras85D genomic sequences with the previously published nucleotide sequence (Neuman-Silberberg et al., Cell 37 (1984) 1027-1033) shows that the positions of the two introns are not conserved relative to the positions of the introns in Dmras64B or in vertebrate ras genes. The Dmras64B and Dmras85D transcripts were analyzed by blot hybridization and shown to be dissimilar. The data suggest that the divergence of the Dmras genes was ancient, and that Dmras85D and Dmras64B have different functions. Brock H W HW eng GENBANK M16123 M16124 M16428 M16429 M16430 M16431 Journal Article

NETHERLANDS Gene 7706761 0 Proto-Oncogene Proteins 0 RNA, Messenger EC 3.6.1.- GTP-Binding Proteins IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Molecular Comparative Study Drosophila melanogaster genetics GTP-Binding Proteins genetics Genes, Structural Oncogenes Proto-Oncogene Proteins genetics Proto-Oncogenes RNA, Messenger genetics Support, Non-U.S. Gov't FBrf0057847 93343899 8343140 1993 09 02 1993 09 02 2000 12 18

0265-9247 15 5 1993 May The specification of sensory neuron identity in Drosophila. 293-8 Different types of sense organs are present on the larva of Drosophila. Several genes that specify the type of sense organ that will form at a particular position have been recently identified. Here we review the functional and molecular analyses of these genes, and summarize the evidence which supports a role in the choice of which type of organ will be formed. Most or all of these genes are required for the appropriate specification of adult as well as larval sense organs, suggesting that the larval and adult systems share many gene requirements. Interestingly, the specifying genes identified so far in the peripheral nervous system are also expressed in subsets of cells in the central nervous system, where they might have similar roles. Laboratorie de Neurobiologie, Université Libre de Bruxelles, Rhode St Genèse, Belgium. Ghysen A A Dambly-Chaudière C C eng Journal Article Review Review, Tutorial

ENGLAND Bioessays 8510851 IM Bar BarH1 BarH2 cut da osn poxn Abdomen innervation Animal Cell Differentiation Drosophila melanogaster anatomy & histology genetics growth & development Gene Expression Regulation Genes Larva anatomy & histology growth & development Morphogenesis genetics Neurons, Afferent Peripheral Nerves anatomy & histology growth & development Sense Organs anatomy & histology growth & development Thorax innervation 42 FBrf0145130 21669015 11810238 2002 01 25 2002 02 19 2003 01 03

1617-4615 266 4 2001 Dec The loss of Drosophila APG4/AUT2 function modifies the phenotypes of cut and Notch signaling pathway mutants. 657-63 A P-element line ( P0997) of Drosophila melanogaster in which the P element disrupts the Drosophila homolog of the Saccharomyces cerevisiae gene APG4/AUT2 was identified during the course of screening for cut ( ct) modifiers. The yeast gene APG4/AUT2 encodes a cysteine endoprotease directed against Apg8/Aut7 and is necessary for autophagy. The P0997 mutation enhances the wing margin loss associated with ct mutations, and also modifies the wing and eye phenotypes of Notch (N), Serrate (Ser), Delta (Dl), Hairless (H), deltex (dx), vestigial (vg) and strawberry notch (sno) mutants. These results therefore suggest an unexpected link between autophagy and the Notch signaling pathway. Institut für Biochemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany. Thumm M M Kadowaki T T eng Journal Article 2001 10 06

Germany Mol Genet Genomics 101093320 0 AUT2 protein 0 CCAAT displacement protein 0 Membrane Proteins 0 Microtubule-Associated Proteins 0 Nuclear Proteins 0 Repressor Proteins 0 notch protein EC 3.4.22 Cysteine Endopeptidases IM Amino Acid Sequence Animal Cysteine Endopeptidases genetics Drosophila physiology Genes, Insect Genetic Complementation Test Membrane Proteins metabolism Microtubule-Associated Proteins genetics Molecular Sequence Data Mutagenesis, Insertional Mutation Nuclear Proteins metabolism Phenotype Repressor Proteins metabolism Saccharomyces cerevisiae genetics Sequence Homology, Amino Acid Signal Transduction genetics Support, Non-U.S. Gov't Wing growth & development FBrf0131381 20556139 11102367 2000 12 28 2001 02 15

0016-6731 156 4 2000 Dec Mutations affecting the development of the peripheral nervous system in Drosophila: a molecular screen for novel proteins. 1691-715 In our quest for novel genes required for the development of the embryonic peripheral nervous system (PNS), we have performed three genetic screens using MAb 22C10 as a marker of terminally differentiated neurons. A total of 66 essential genes required for normal PNS development were identified, including 49 novel genes. To obtain information about the molecular nature of these genes, we decided to complement our genetic screens with a molecular screen. From transposon-tagged mutations identified on the basis of their phenotype in the PNS we selected 31 P-element strains representing 26 complementation groups on the second and third chromosomes to clone and sequence the corresponding genes. We used plasmid rescue to isolate and sequence 51 genomic fragments flanking the sites of these P-element insertions. Database searches using sequences derived from the ends of plasmid rescues allowed us to assign genes to one of four classes: (1) previously characterized genes (11), (2) first mutations in cloned genes (1), (3) P-element insertions in genes that were identified, but not characterized molecularly (1), and (4) novel genes (13). Here, we report the cloning, sequence, Northern analysis, and the embryonic expression pattern of candidate cDNAs for 10 genes: astray, chrowded, dalmatian, gluon, hoi-polloi, melted, pebble, skittles, sticky ch1, and vegetable. This study allows us to draw conclusions about the identity of proteins required for the development of the nervous system in Drosophila and provides an example of a molecular approach to characterize en masse transposon-tagged mutations identified in genetic screens. Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. prokopenko@salk.edu Prokopenko S N SN He Y Y Lu Y Y Bellen H J HJ eng Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 DNA, Complementary 0 Insect Proteins 0 Nerve Tissue Proteins IM Animal Cell Differentiation Cloning, Molecular DNA Transposable Elements genetics DNA, Complementary genetics Drosophila melanogaster embryology genetics Embryo, Nonmammalian metabolism Gene Expression Profiling Genes, Structural, Insect Genetic Complementation Test In Situ Hybridization Insect Proteins genetics physiology Mutagenesis, Insertional Nerve Tissue Proteins genetics physiology Neurons chemistry Peripheral Nervous System embryology Support, Non-U.S. Gov't FBrf0102967 98278816 9611209 1998 09 10 1998 09 10 2000 12 18

0016-6731 149 2 1998 Jun Two sites in the Delta gene region contribute to naturally occurring variation in bristle number in Drosophila melanogaster. 999-1017 A restriction enzyme survey of a 57-kb region including the gene Delta uncovered 53 polymorphic molecular markers in a sample of 55 naturally occurring chromosomes. A permutation test, which assesses the significance of the molecular marker with the largest effect on bristle variation in four genetic backgrounds relative to permuted data-sets, found two sites that were independently associated with variation in bristle number. A common site in the second intron of Delta affected only sternopleural bristle number, and another common site in the fifth intron affected only abdominal bristle number in females. Under an additive genetic model, the polymorphism in the second intron may account for 12% of the total genetic variation in sternopleural bristle number due to third chromosomes, and the site in the fifth intron may account for 6% of the total variation in female abdominal bristle number due to the third chromosomes. These results suggest the following: (1) models that incorporate balancing selection are more consistent with observations than deleterious mutation-selection equilibrium models, (2) mapped quantitative trait loci of large effect may not represent a single variable site at a genetic locus, and (3) linkage disequilibrium can be used as a tool for understanding the molecular basis of quantitative variation. Center for Population Biology, University of California, Davis, California 95616, USA. tdlong@ucdavis.edu Long A D AD Lyman R F RF Langley C H CH Mackay T F TF eng GM45146 GM NIGMS GM45344 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Genetic Markers 0 Membrane Proteins 0 delta protein IM Animal Chromosomes genetics Conserved Sequence Drosophila melanogaster genetics Female Genes, Structural, Insect Genetic Markers Likelihood Functions Linear Models Linkage Disequilibrium Male Membrane Proteins genetics Phenotype Polymorphism, Restriction Fragment Length Restriction Mapping Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Variation (Genetics) FBrf0058456 93154487 8428612 1993 03 05 1993 03 05 2000 12 18

0014-4754 49 1 1993 Jan 15 Heat shock proteins in three related Drosophila species belonging to the obscura group. 54-6 The effect of heat shock on protein synthesis in three related Drosophila species belonging to the obscura group was analyzed on SDS-acrylamide gels. Four major heat shock proteins (hsps) were found in these species, in which synthesis reaches a maximum at 34 degrees C. Although the higher molecular weight proteins are conserved, differences in size were found for the small hsps in these species. By means of in situ hybridization using D. melanogaster probes for the small hsp genes, it was inferred that the small hsp genes of the obscura group species are clustered at the 27A locus in all three species. Department of Genetics, Faculty of Biological Sciences, University of Valencia, Spain. Moltó M D MD Pascual L L Martínez-Sebastián M J MJ de Frutos R R eng Journal Article

SWITZERLAND Experientia 0376547 0 Heat-Shock Proteins IM Animal Drosophila genetics metabolism Heat Heat-Shock Proteins analysis biosynthesis genetics In Situ Hybridization Molecular Weight Support, Non-U.S. Gov't FBrf0093544 97248612 9092663 1997 05 23 1997 05 23 2002 11 01

0305-1048 25 8 1997 Apr 15 NMR analysis of the hydrogen bonding interactions of the RNA-binding domains of the Drosophila sex-lethal protein with target RNA fragments with site-specific [3-15N]uridine substitutions. 1565-9 It has been reported that a 183 residue fragment, consisting of the two RNA-binding domains (RBD1- RBD2) of the Drosophila melanogster Sex-lethal (Sxl) protein, strongly binds an oligonucleotide of the target RNA sequence (5'-GUUUUUUUUC-3') that regulates alternative splicing, and forms four or five hydrogen bonds with the imino groups of the RNA. In the present study, we used site-directed mutagenesis to improve the solubility of the didomain fragment of Sxl, and confirmed that this mutant fragment forms hydrogen bonds with the target RNA in the same manner as that of the wild-type fragment. The mutant fragment was shown to bind the cognate RNA sequences GUUUUUUUUC and AUUUUUUUUC more tightly than UUUUUUUUC. By using a [3-15N]uridine phosphoramidite, we synthesized a series of15N-labeled target RNAs, in which one of the uridine residues was specifically replaced by [3-15N]uridine. By observing the imino1H-15N coupling of the labeled uridine residue, we assigned all four of the hydrogen-bonded imino protons to U1, U2, U5 and U6, respectively, of the target RNA. The imino protons of U2 and U6 exhibited nuclear Overhauser effects with aliphatic protons of the protein. All these results indicate that the A/G, U1, U2, U5 and U6 residues in the target sequence of (G/A)UUUUUUUU are specifically recognized by the two RNA-binding domains of the Sxl protein. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan. Kim I I Muto Y Y Inoue M M Watanabe S S Kitamura A A Yokoyama S S Hosono K K Takaku H H Ono A A Kainosho M M Sakamoto H H Shimura Y Y eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 Insect Hormones 0 Nitrogen Isotopes 0 Oligoribonucleotides 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 58-96-8 Uridine 63231-63-0 RNA IM Animal Base Sequence Binding Sites Drosophila melanogaster Hydrogen Bonding Insect Hormones chemistry Magnetic Resonance Spectroscopy Nitrogen Isotopes Oligoribonucleotides chemistry metabolism RNA chemistry metabolism RNA-Binding Proteins chemistry metabolism Support, Non-U.S. Gov't Uridine FBrf0053040 91048857 2122562 1990 12 12 1990 12 12 2000 12 18

0168-9525 6 8 1990 Aug Germ-line sex determination in Drosophila melanogaster. 259-64 In Drosophila melanogaster, the mechanism of sex determination is substantially different in the germ line and in the soma. In the germ line, the process is not completely cell-autonomous, but requires some signals from the soma. Only some of the genes involved in somatic sex determination are also needed for germ cell development. Recent genetic studies have identified loci required for germ-line sex determination. Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106. Pauli D D Mahowald A P AP eng HD-17608 HD NICHD Journal Article Review Review, Tutorial

ENGLAND Trends Genet 8507085 IM Animal Drosophila melanogaster genetics Epistasis, Genetic Female Gene Expression Regulation Genes, Regulator Infertility, Female genetics Male Mosaicism Oogenesis Ovarian Neoplasms genetics Sex Determination (Analysis) Spermatogenesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 42 FBrf0126808 20200386 10734040 2000 05 04 2000 05 04 2000 12 18

0021-9258 275 13 2000 Mar 31 Notch responds differently to Delta and Wingless in cultured Drosophila cells. 9099-101 Notch, a cell surface receptor, is required for producing different types of cells during development of Drosophila melanogaster. Notch activates expression of one set of genes in response to ligand Delta and another set of genes in response to ligand Wingless. The means by which Notch initiates these different intracellular activities was examined in this study. Cultured cells expressing Notch were treated with Delta or Wingless, and the effect on Notch was examined by Western blotting. Treatment of cells with Delta resulted in accumulation of approximately 120-kDa Notch intracellular domain molecules in the cytoplasmic fraction. This form of Notch did not accumulate in cells treated with Wingless, but the approximately 350-kDa full-length Notch molecules accumulated. These results indicate that N responds differently to binding by Delta and Wingless, and suggest that although the Delta signal is transduced by the Notch intracellular domain released from the plasma membrane, the Wingless signal is transduced by the Notch intracellular domain associated with the plasma membrane. Laboratory of Genetics, The Rockefeller University, New York, New York 10021, USA. wesleyc@rockvax.rockefeller.edu Wesley C S CS Saez L L eng GM 25103 GM NIGMS Journal Article

UNITED STATES J Biol Chem 2985121R 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 delta protein 0 notch protein 117758-26-6 wingless protein, Drosophila IM Animal Cell Nucleus metabolism Cells, Cultured Drosophila melanogaster cytology metabolism Membrane Proteins metabolism Proto-Oncogene Proteins metabolism Signal Transduction Support, U.S. Gov't, P.H.S. FBrf0056310 93051315 1427063 1992 12 08 1992 12 08 2000 12 18

0831-2796 35 5 1992 Oct Genetic analysis of heat shock response in three Drosophila species of the obscura group. 870-80 Heat shock response was investigated in three species of the obscura group of the Drosophila genus (D. subobscura, D. guanche, and D. madeirensis) by chromosome cytology analysis and [3H]uridine labeling. A set of eight puffs (2C, 15DE, 18C, 27A, 31CD, 85AB, 89A, and 94A) were induced after heat treatments in each of the three species; 18C, 27A, 89A, and 94A were the most heavily labeled in the autoradiograms after the induced conditions. From the in situ results using the major heat shock genes of D. melanogaster as a probe, it was inferred that the 18C, 94A, 89A, and 27A loci of the three obscura group species are homologous to D. melanogaster loci, which contain, HSP82, HSP70, HSP68, and HSPs encoding for the small heat shock proteins, respectively. When this organization was compared with that of D. melanogaster, fewer evolutionary changes, mainly gene duplications, were found to have occurred in the obscura group species than in the D. melanogaster group. In the three species analyzed in this work, as well as in the other Drosophila species studied, the heat shock genes are distributed on D and E Muller's elements, behaving as single copy genes that do not move around the genome. Department of Genetics, University of València, Spain. Moltó M D MD Pascual L L Martínez-Sebastián M J MJ de Frutos R R eng Journal Article

CANADA Genome 8704544 0 Heat-Shock Proteins 0 Molecular Probes IM Animal Chromosome Banding Chromosomes ultrastructure Drosophila genetics Drosophila melanogaster genetics Evolution Heat Heat-Shock Proteins genetics Molecular Probes Support, Non-U.S. Gov't FBrf0109806 99396705 10393119 1999 09 21 1999 09 21 2000 12 18

0950-1991 126 15 1999 Aug Proximal to distal cell communication in the Drosophila leg provides a basis for an intercalary mechanism of limb patterning. 3407-13 Proximodistal patterning in the Drosophila leg is elaborated from the circular arrangement of the proximal domain expressing escargot and homothorax, and the distal domain expressing Distal-less that are allocated during embryogenesis. The distal domain differentiates multiply segmented distal appendages by activating additional genes such as dachshund. Secreted signaling molecules Wingless and Decapentaplegic, expressed along the anterior-posterior compartment boundary, are required for activation of Distal-less and dachshund and repression of homothorax in the distal domain. However, whether Wingless and Decapentaplegic are sufficient for the circular pattern of gene expression is not known. Here we show that a proximal gene escargot and its activator homothorax regulate proximodistal patterning in the distal domain. Clones of cells expressing escargot or homothorax placed in the distal domain induce intercalary expression of dachshund in surrounding cells and reorient planar cell polarity of those cells. Escargot and homothorax-expressing cells also sort out from other cells in the distal domain. We suggest that inductive cell communication between the proximodistal domains, which is maintained in part by a cell-sorting mechanism, is the cellular basis for an intercalary mechanism of the proximodistal axis patterning of the limb. National Institute of Genetics, Graduate University for Advanced Studies, Mishima, Shizuoka-ken 411-8540, Japan. Goto S S Hayashi S S eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Nuclear Proteins 0 Transcription Factors 0 dachshund protein 0 homothorax protein 0 snail protein IM Animal Body Patterning Cell Communication physiology DNA-Binding Proteins genetics Drosophila melanogaster cytology genetics growth & development Extremities growth & development Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Homeodomain Proteins genetics Models, Biological Nuclear Proteins genetics Regeneration Signal Transduction Support, Non-U.S. Gov't Transcription Factors genetics FBrf0135819 21130079 11234428 2001 03 07 2001 04 19 2001 11 19

0016-6758 37 1 2001 Jan [Some regularities in the genetic control of the stress reaction in Drosophila] 73-80 The heat-shock response was studied in Drosophila virilis strains with normal and impaired neurohormonal stress reaction. Flies from the latter strain were shown to have the impaired heat-shock response. In this strain, transcription of the heat shock gene hsp83 is reduced and synthesis of all heat shock proteins is suppressed. The neurohormonal stress reaction (status of dopamine, octopamine, and juvenile hormone metabolic systems) was examined in D. melanogaster strains having normal and impaired heat-shock response. The impairment of this response did not prevent the development of the stress reaction: in flies of both strains, the stress exposure resulted in an increase in the dopamine content and in a decrease in the activity of tyrosine decarboxylase (the first enzyme of dopamine synthesis) and in the level of juvenile hormone degradation. However, stress reactivity in mutant individuals differed from that in flies that did not carry stress-related mutations. Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, 630090 Russia. iraushen@bionet.nsc.ru Raushenbakh I Iu IIu Gruntenko N E NE Vasenkova I A IA Khlebodarova T M TM Sukhanova M Zh MZh Korochkin L I LI rus Journal Article O nekotorykh zakonomernostiakh geneticheskogo kontrolia stress-reaktsii drozofily.

Russia Genetika 0047354 0 Heat-Shock Proteins 0 Juvenile Hormones 104-14-3 Octopamine 51-61-6 Dopamine IM Animal Dopamine physiology Drosophila genetics physiology English Abstract Heat-Shock Proteins genetics Juvenile Hormones physiology Octopamine physiology Stress genetics FBrf0051631 90107945 2104801 1990 02 21 1990 02 21 2000 12 18

0261-4189 9 1 1990 Jan The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern. 207-16 We have identified a Drosophila zinc-finger protein, which binds to a number of sites in the transcriptional control regions of the pair-rule gene fushi-tarazu (ftz). The expression pattern of the mRNA that encodes this protein is essentially complementary to that of ftz both prior to blastoderm formation and during germband extension. We propose that the protein may function by repressing inappropriate segmentation gene transcription during embryogenesis. The gene encoding this ftz promoter-binding protein has been named tramtrack (ttk). MRC Laboratory of Molecular Biology, Cambridge UK. Harrison S D SD Travers A A AA eng GENBANK X17121 Journal Article

ENGLAND EMBO J 8208664 0 DNA-Binding Proteins 0 Metalloproteins 0 RNA, Messenger 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Binding Sites Cloning, Molecular DNA genetics metabolism DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Gene Expression Metalloproteins genetics metabolism Molecular Sequence Data RNA, Messenger genetics Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't Transcription, Genetic Zygote metabolism FBrf0136756 21385274 11493638 2001 08 08 2001 12 07

0021-9533 114 Pt 11 2001 Jun The Drosophila Dpit47 protein is a nuclear Hsp90 co-chaperone that interacts with DNA polymerase alpha. 2015-25 Hsp90 is gaining increasing importance as a protein involved in controlling the normal functioning of the cell. To do this it apparently interacts with a battery of co-chaperone proteins that are involved in both substrate recognition and the progression of the Hsp90 catalytic pathway. In this report we have identified the Drosophila Dpit47 protein (DNA polymerase interacting tpr containing protein of 47 kDa) through its interaction with the DNA polymerase alpha. This protein is a predominantly nuclear protein, which forms a tight and stoichiometric interaction with Hsp90 and shows interaction with Hsp70. It also has substantial homology to other known Hsp90 co-chaperones, e.g. CNS1 and hop1, making it likely that this protein also functions as an Hsp90 co-chaperone. The interaction with the DNA polymerase alpha is not related to the special situation in early embryos where there are large amounts of maternal protein stockpiles of the polymerase, as it occurs to the same level in early and late embryos and also in proliferating cell culture. However, it does not occur in quiescent cells, making it likely that the protein is related to proliferation. This is also consistent with Dpit47 expression being higher in proliferating cells. The interaction between the Dpit47 and the polymerase takes place predominantly in the nucleoplasm, and seems to involve several subunits of the polymerase in comparable amounts, making it unlikely that it is solely required for the assembly of the polymerase complex. The polymerase can also be seen to interact with Hsp90, and the interaction between Dpit47 and the polymerase is increased by the specific Hsp90 inhibitor geldanamycin. This suggests that a complex of the Dpit47, Hsp90 and DNA polymerase exists in the cell. The interaction between DNA polymerase alpha and Dpit47 completely inhibits the activity of the polymerase. These results suggest that Hsp90 acts as a chaperone for DNA polymerase alpha and that this interaction is mediated through the novel co-chaperone Dpit47. This provides the first suggestion of a role for chaperones in DNA replication in higher eukaryotes. Department of Biochemistry and Immunology, St Georges Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK. Crevel G G Bates H H Huikeshoven H H Cotterill S S eng Journal Article

England J Cell Sci 0052457 0 Chromatin 0 Heat-Shock Proteins 70 0 Heat-Shock Proteins 90 0 Molecular Chaperones 0 Nuclear Proteins 0 Protein Subunits 0 Quinones 30562-34-6 geldanamycin EC 2.7.7.- DNA Polymerase I IM Amino Acid Motifs Amino Acid Sequence Animal Cell Division Chromatin metabolism Cytoplasm metabolism DNA Polymerase I metabolism Drosophila melanogaster cytology embryology genetics metabolism Gene Expression Regulation, Developmental Heat-Shock Proteins 70 metabolism Heat-Shock Proteins 90 chemistry genetics metabolism Immunohistochemistry Microscopy, Confocal Molecular Chaperones chemistry genetics metabolism Molecular Sequence Data Nuclear Proteins chemistry genetics metabolism Protein Binding drug effects Protein Subunits Quinones pharmacology Sequence Alignment Support, Non-U.S. Gov't Two-Hybrid System Techniques FBrf0038303 82267722 6809878 1982 10 21 1982 10 21 2000 12 18

0022-0752 68 1982 Apr A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. 37-57 The polarity mutants pk, sple, mwh, fz and in alter the orientations of cuticular processes in several regions of the body. The mutant polarity patterns are constant and do not result from alterations in cell lineage. Polarity patterns are locus specific rather than allele specific (new alleles express the same polarity patterns as the original alleles). In the wing, polarity formation is largely cell autonomous and is independent of the anteroposterior compartment boundary. By genetic and physiological manipulation it is shown that the mutant polarity patterns are unaffected by the size of the wing blade or the number of cells that form it. Mutants which remove parts of the wing margin or alter the distribution pattern of wing veins do not alter the mutant polarity patterns. Thus, neither the wing margins nor the pattern of vein tissue act as spatial references for polarity formation. The determination of mutant polarity patterns is not dependent on the overall topology of the wing blade but is region-specific. The mutants affect several independent functions. The possible wild-type function of the loci in polarity formation is discussed. Gubb D D García-Bellido A A eng Journal Article

ENGLAND J Embryol Exp Morphol 7906439 IM Alleles Animal Chromosome Mapping Drosophila melanogaster Morphogenesis Mosaicism Mutation Phenotype Polarity of Translation Skin growth & development ultrastructure Support, Non-U.S. Gov't Temperature Translation, Genetic Wing growth & development FBrf0074884 94299520 8027064 1994 08 08 1994 08 08 2000 12 18

0021-9258 269 27 1994 Jul 8 Purification and characterization of eukaryotic polypeptide chain initiation factor 4F from Drosophila melanogaster embryos. 18047-52 The eukaryotic polypeptide chain initiation factor 4F (eIF-4F), purified by m7GTP-Sepharose chromatography from whole extracts of Drosophila melanogaster embryos, consists of two subunits, the previously identified eIF-4E (35 kDa) (Maroto, F. G., and Sierra, J. M. (1989) Mol. Cell. Biol. 9, 2181-2190) and another of 200 kDa. Both subunits cosedimented through a sucrose density gradient containing 0.5 M KCl. In contrast to rabbit reticulocyte eIF-4F, we did not find any RNA-dependent ATPase associated with the Drosophila factor. As shown previously for eIF-4E, the p200 subunit was also required for the translation of endogenous mRNAs in cell-free systems from Drosophila embryos. Only the eIF-4E subunit was able to cross-link to the m7G cap structure. However, an efficient cross-linking of the p200 subunit to an uncapped mRNA was observed. Both subunits were phosphorylated in vitro by protein kinase C from rat brain. As an extension of our previous results (Zapata, J. M., Maroto, F. G., and Sierra, J. M. (1991) J. Biol. Chem. 266, 16007-16014) we found that the translation of the heat shock mRNAs was independent of both of the eIF-4F subunits. Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Madrid, Spain. Zapata J M JM Martínez M A MA Sierra J M JM eng Journal Article

UNITED STATES J Biol Chem 2985121R 0 Peptide Fragments 0 Peptide Initiation Factors 0 eIF-4 0 initiation factor 4F component p220 IM Animal Chromatography, Gel Drosophila melanogaster embryology Peptide Fragments isolation & purification metabolism Peptide Initiation Factors isolation & purification metabolism Rabbits Support, Non-U.S. Gov't Temperature Translation, Genetic FBrf0082353 95399315 7669694 1995 10 13 1995 10 13 2001 11 02

0925-4773 51 1 1995 May Minor-myosin, a novel myosin isoform synthesized preferentially in Drosophila testis is encoded by the muscle myosin heavy chain gene. 67-81 Searching for structural proteins involved in spermatogenesis of Drosophila, we found a novel myosin isoform in the testis of Drosophila hydei and D. melanogaster. The transcript encoding this isoform, which we called 'minor-myosin', initiates within the intron between exons 12 and 13 of the muscle myosin heavy chain (mMHC) gene. Minor-myosin contains a common myosin tail but no ordinary myosin head domain. Instead, it has a short N-terminal domain which displays similarity with the N-termini of certain myosin light chain proteins. Western blots with male germ line mutants showed that the novel mMHC isoform is synthesized in the male germ cells, mainly postmeiotically. However, minor-myosin is not testis-specific, as it is expressed at a low level in the fly carcasses. The possible functions of the myosin isoform in the male germ line are discussed. Department of Molecular and Developmental Genetics, Faculty of Sciences, Catholic University of Nijmegen, Toernooiveld, The Netherlands. Miedema K K Hanske M M Akhmanova A A Bindels P P Hennig W W eng GENBANK X77570 Journal Article

IRELAND Mech Dev 9101218 0 RNA, Messenger EC 3.6.1.4 Myosins IM MHC Amino Acid Sequence Animal Base Sequence Blotting, Northern Blotting, Western Cytoplasm immunology metabolism Drosophila genetics metabolism Female Genes, Insect Introns Male Microscopy, Immunoelectron Molecular Sequence Data Mutation Myosins biosynthesis genetics Ovary metabolism Peptide Mapping RNA, Messenger analysis genetics Sequence Alignment Spermatids metabolism ultrastructure Spermatogenesis Support, Non-U.S. Gov't Testis metabolism FBrf0155682 22474010 12586057 2003 02 14 2003 03 14

1534-5807 4 2 2003 Feb A new trick for Cyclin-Cdk: activation of STAT. 148-9 New work in Drosophila demonstrates that cdk4 loss causes phenotypes similar to the loss of JAK/STAT pathway components. Cdk4 overexpression can bypass requirements for JAK but not STAT. These results demonstrate a new function for Cdk4 and a new mode of STAT activation. Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 Wolfe Street, Baltimore, MD 21205, USA. Silver Debra L DL Montell Denise J DJ eng Comment Journal Article Review Review, Tutorial

United States Dev Cell 101120028 0 DNA-Binding Proteins 0 Transcription Factors EC 2.7.1.- p34PSK-J3 kinase EC 2.7.1.37 Cyclin-Dependent Kinases IM Dev Cell. 2003 Feb;4(2):179-90 12586062 Animal Cell Cycle physiology Cyclin-Dependent Kinases physiology DNA-Binding Proteins metabolism Drosophila melanogaster Female Signal Transduction Transcription Factors metabolism 8 FBrf0068603 94170368 8124709 1994 04 08 1994 04 08 2003 06 16

0092-8674 76 4 1994 Feb 25 The spätzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. 677-88 spätzle is a maternal effect gene required in the signal transduction pathway that establishes the dorsal-ventral pattern of the Drosophila embryo. spätzle acts immediately upstream of the membrane protein Toll in the genetic pathway, suggesting that spätzle could encode the ventrally localized ligand that activates the receptor activity of Toll. The spätzle gene encodes a novel secreted protein that appears to require activation by a proteolytic processing reaction, which is controlled by the genes that act upstream of spätzle in the genetic pathway. We propose that proteolytic processing of the spätzle protein is confined to the ventral side of the embryo and that the localization of processed spätzle determines where the receptor, Toll, is active. Department of Molecular and Cell Biology, University of California, Berkeley 94720. Morisato D D Anderson K V KV eng GENBANK U05850 GM 35437 GM NIGMS Journal Article

UNITED STATES Cell 0413066 0 DNA Primers 0 Insect Hormones 0 Membrane Glycoproteins 0 spatzle protein, Drosophila 118929-01-4 Toll protein, Drosophila IM Toll spz Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA Mutational Analysis DNA Primers chemistry Drosophila melanogaster embryology Genes, Structural, Insect Insect Hormones genetics physiology Membrane Glycoproteins physiology Molecular Sequence Data Molecular Weight Morphogenesis Protein Processing, Post-Translational Restriction Mapping Sequence Deletion Signal Transduction Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0148976 22027692 12032070 2002 05 28 2002 07 19 2003 01 09

0261-4189 21 11 2002 Jun 3 The Toll and Imd pathways are the major regulators of the immune response in Drosophila. 2568-79 Microarray studies have shown recently that microbial infection leads to extensive changes in the Drosophila gene expression programme. However, little is known about the control of most of the fly immune-responsive genes, except for the antimicrobial peptide (AMP)-encoding genes, which are regulated by the Toll and Imd pathways. Here, we used oligonucleotide microarrays to monitor the effect of mutations affecting the Toll and Imd pathways on the expression programme induced by septic injury in Drosophila adults. We found that the Toll and Imd cascades control the majority of the genes regulated by microbial infection in addition to AMP genes and are involved in nearly all known Drosophila innate immune reactions. However, we identified some genes controlled by septic injury that are not affected in double mutant flies where both Toll and Imd pathways are defective, suggesting that other unidentified signalling cascades are activated by infection. Interestingly, we observed that some Drosophila immune-responsive genes are located in gene clusters, which often are transcriptionally co-regulated. Centre de Génétique Moléculaire, CNRS, F-91198 Gif-sur-Yvette, France. De Gregorio Ennio E Spellman Paul T PT Tzou Phoebe P Rubin Gerald M GM Lemaitre Bruno B eng Journal Article

England EMBO J 8208664 0 Drosophila Proteins 0 Receptors, Cell Surface 0 immune deficiency protein, Drosophila 118929-01-4 Toll protein, Drosophila IM Animal Dose-Response Relationship, Drug Drosophila Proteins physiology Drosophila melanogaster immunology metabolism Gene Expression Regulation Genome Models, Biological Mutation Oligonucleotide Array Sequence Analysis Protein Binding Receptors, Cell Surface physiology Support, Non-U.S. Gov't Time Factors Transcription, Genetic FBrf0105339 99029843 9814706 1998 12 07 1998 12 07 2003 06 16

0092-8674 95 3 1998 Oct 30 An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. 355-64 Intercellular signaling through the EGF receptor (EGFR) patterns the Drosophila egg. The TGF alpha-like ligand Gurken signals from the oocyte to the receptor in the overlying somatic follicle cells. We show that in the dorsal follicle cells this initial paracrine signaling event triggers an autocrine amplification by two other EGFR ligands, Spitz and Vein. Spitz only becomes an effective ligand in the presence of the multitransmembrane domain protein Rhomboid. Consequent high-level EGFR activation leads to localized expression of the diffusible inhibitor Argos, which alters the profile of signaling. This sequential activation, amplification, and local inhibition of the EGFR forms an autoregulatory cascade that leads to the splitting of an initial single peak of signaling into two, thereby patterning the egg. MRC Laboratory of Molecular Biology, Cambridge, England. Wasserman J D JD Freeman M M eng Journal Article

UNITED STATES Cell 0413066 0 Eye Proteins 0 Insect Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Rho protein, Drosophila 0 gurken protein, Drosophila 0 rho-2 protein, Drosophila 147954-53-8 gil protein 148175-53-5 spitz protein 182299-68-9 vein protein, Drosophila 76057-06-2 Transforming Growth Factors EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 3.6.1.- ras Proteins IM Cell. 1998 Oct 30;95(3):291-4 9814698 Animal Autocrine Communication Body Patterning Drosophila melanogaster genetics metabolism Egg Shell growth & development Eye Proteins genetics metabolism Female Genes, Essential Insect Proteins genetics metabolism Membrane Proteins genetics metabolism Models, Biological Mutation Nerve Tissue Proteins genetics metabolism Oocytes cytology growth & development Oogenesis Ovarian Follicle metabolism Paracrine Communication Phenotype Receptor, Epidermal Growth Factor antagonists & inhibitors genetics metabolism Signal Transduction Support, Non-U.S. Gov't Transforming Growth Factors genetics metabolism ras Proteins genetics FBrf0128554 20341320 10880479 2000 08 21 2000 08 21 2000 12 18

0016-6731 155 3 2000 Jul A physical map of the polytenized region (101EF-102F) of chromosome 4 in Drosophila melanogaster. 1175-83 Chromosome 4, the smallest autosome ( approximately 5 Mb in length) in Drosophila melanogaster contains two major regions. The centromeric domain ( approximately 4 Mb) is heterochromatic and consists primarily of short, satellite repeats. The remaining approximately 1.2 Mb, which constitutes the banded region (101E-102F) on salivary gland polytene chromosomes and contains the identified genes, is the region mapped in this study. Chromosome walking was hindered by the abundance of moderately repeated sequences dispersed along the chromosome, so we used many entry points to recover overlapping cosmid and BAC clones. In situ hybridization of probes from the two ends of the map to polytene chromosomes confirmed that the cloned region had spanned the 101E-102F interval. Our BAC clones comprised three contigs; one gap was positioned distally in 102EF and the other was located proximally at 102B. Twenty-three genes, representing about half of our revised estimate of the total number of genes on chromosome 4, were positioned on the BAC contigs. A minimal tiling set of the clones we have mapped will facilitate both the assembly of the DNA sequence of the chromosome and a functional analysis of its genes. Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada. john.locke@ualberta.ca Locke J J Podemski L L Aippersbach N N Kemp H H Hodgetts R R eng Journal Article

UNITED STATES Genetics 0374636 0 Cosmids IM Animal Chromosome Walking Chromosomes genetics Chromosomes, Bacterial genetics Cloning, Molecular Cosmids genetics Drosophila melanogaster genetics In Situ Hybridization Physical Chromosome Mapping Restriction Mapping Support, Non-U.S. Gov't FBrf0097687 97370012 9226453 1997 08 25 1997 08 25 2002 10 21

0950-1991 124 14 1997 Jul Genetic basis of the formation and identity of type I and type II neurons in Drosophila embryos. 2819-28 The embryonic peripheral nervous system of Drosophila contains two main types of sensory neurons: type I neurons, which innervate external sense organs and chordotonal organs, and type II multidendritic neurons. Here, we analyse the origin of the difference between type I and type II in the case of the neurons that depend on the proneural genes of the achaete-scute complex (ASC). We show that, in Notch- embryos, the type I neurons are missing while type II neurons are produced in excess, indicating that the type I/type II choice relies on Notch-mediated cell communication. In contrast, both type I and type II neurons are absent in numb- embryos and after ubiquitous expression of tramtrack, indicating that the activity of numb and the absence of tramtrack are required to produce both external sense organ and multidendritic neural fates. The analysis of string- embryos reveals that when the precursors are unable to divide they differentiate mostly into type II neurons, indicating that the type II is the default neuronal fate. We also report a new mutant phenotype where the ASC-dependent neurons are converted into type II neurons, providing evidence for the existence of one or more genes required for maintaining the alternative (type I) fate. Our results suggest that the same mechanism of type I/type II specification may operate at a late step of the ASC-dependent lineages, when multidendritic neurons arise as siblings of the external sense organ neurons and, at an early step, when other multidendritic neurons precursors arise as siblings of external sense organ precursors. Laboratoire de Génétique du Développement, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium. mvervoor@dbm.ulb.ac.be Vervoort M M Merritt D J DJ Ghysen A A Dambly-Chaudière C C eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Juvenile Hormones 0 Membrane Proteins 0 Transcription Factors 0 achaete protein, Drosophila 0 notch protein 0 scute protein, Drosophila 0 tramtrack protein 126805-88-7 numb protein IM Animal DNA-Binding Proteins genetics Drosophila melanogaster cytology embryology genetics Juvenile Hormones genetics Membrane Proteins genetics Morphogenesis Mutation Neurons cytology Sense Organs cytology embryology Support, Non-U.S. Gov't Transcription Factors genetics X Chromosome FBrf0081989 95354655 7628438 1995 09 07 1995 09 07 2000 12 18

0261-4189 14 14 1995 Jul 17 The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. 3373-84 We report the cloning and primary structure of the Drosophila insulin receptor gene (inr), functional expression of the predicted polypeptide, and the isolation of mutations in the inr locus. Our data indicate that the structure and processing of the Drosophila insulin proreceptor are somewhat different from those of the mammalian insulin and IGF 1 receptor precursors. The INR proreceptor (M(r) 280 kDa) is processed proteolytically to generate an insulin-binding alpha subunit (M(r) 120 kDa) and a beta subunit (M(r) 170 kDa) with protein tyrosine kinase domain. The INR beta 170 subunit contains a novel domain at the carboxyterminal side of the tyrosine kinase, in the form of a 60 kDa extension which contains multiple potential tyrosine autophosphorylation sites. This 60 kDa C-terminal domain undergoes cell-specific proteolytic cleavage which leads to the generation of a total of four polypeptides (alpha 120, beta 170, beta 90 and a free 60 kDa C-terminus) from the inr gene. These subunits assemble into mature INR receptors with the structures alpha 2(beta 170)2 or alpha 2(beta 90)2. Mammalian insulin stimulates tyrosine phosphorylation of both types of beta subunits, which in turn allows the beta 170, but not the beta 90 subunit, to bind directly to p85 SH2 domains of PI-3 kinase. It is likely that the two different isoforms of INR have different signaling potentials. Finally, we show that loss of function mutations in the inr gene, induced by either a P-element insertion occurring within the predicted ORF, or by ethylmethane sulfonate treatment, render pleiotropic recessive phenotypes that lead to embryonic lethality. The activity of inr appears to be required in the embryonic epidermis and nervous system among others, since development of the cuticle, as well as the peripheral and central nervous systems are affected by inr mutations. Department of Pharmacology, New York University Medical Center, NY 10016, USA. Fernandez R R Tabarini D D Azpiazu N N Frasch M M Schlessinger J J eng GENBANK U28136 HD 30832 HD NICHD Journal Article

ENGLAND EMBO J 8208664 0 Carrier Proteins 0 INR protein 0 Protein Precursors 9007-49-2 DNA EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Insulin IM inr Amino Acid Sequence Animal Base Sequence Carrier Proteins genetics metabolism Cell Line DNA Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Insect Human Larva growth & development metabolism Molecular Sequence Data Mutation Nervous System embryology Phenotype Protein Precursors genetics metabolism Protein Processing, Post-Translational Protein-Tyrosine Kinase genetics metabolism Receptor, Insulin genetics metabolism Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0075981 95071325 7980478 1994 12 20 1994 12 20 2000 12 18

0265-9247 16 10 1994 Oct The regulation of the yolk protein genes, a family of sex differentiation genes in Drosophila melanogaster. 745-52 There are many obvious morphological and behavioural differences between male and female Drosophila, whose differing phenotypes are produced by a hierarchy of sex determination genes. These genes have been well characterised at the genetic and molecular level. Similarly, a number of sex-specific differentiation genes have been characterised, such as the chorion and vitelline membrane genes in females and the sex peptide and other accessory gland proteins in males. Despite the depth of these parallel studies, there is only one example of a direct link between the sex determination pathway and the downstream sex differentiation genes, namely the regulation of the female-specific yolk protein genes. The yolk proteins are synthesised in the fat body and ovarian follicle cells of the adult female and are subsequently transported to the oocyte where they are stored for utilization during embryogenesis. The expression of the yolk protein genes is not entirely controlled by the sex determination hierarchy, as several different regulatory pathways must interact to direct their correct sexual, temporal and spatial regulation during development. Division of Biological Sciences, University of Edinburgh, UK. Bownes M M eng Journal Article Review Review, Academic

ENGLAND Bioessays 8510851 0 Egg Proteins IM Adipose Tissue metabolism Animal Drosophila melanogaster genetics physiology Egg Proteins biosynthesis Female Gene Expression Regulation Male Multigene Family Mutagenesis Sex Determination (Analysis) Sex Differentiation X Chromosome Y Chromosome 68 FBrf0155986 22347597 12459721 2002 12 02 2003 01 15

1471-0056 3 12 2002 Dec Evolution of development in closely related species of flies and worms. 907-17 One of the main challenges in evolutionary biology is to identify the molecular changes that underlie phenotypic differences that are of evolutionary significance. Comparative studies of early development have shown that changes in the spatio-temporal use of regulatory genes, as well as changes in the specificity of regulatory proteins, are correlated with important differences in morphology between phylogenetically distant species. However, it is not known how such changes take place in natural populations, and whether they result from a single, or many small, additive events. Extending this approach to the study of development of closely related species promises to enrich this debate. Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. pas49@cam.ac.uk Simpson Pat P eng Journal Article Review Review, Tutorial

England Nat Rev Genet 100962779 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Homeodomain Proteins 0 Trans-Activators 0 Transcription Factors 0 bicoid protein, Drosophila 0 hunchback protein, Drosophila 0 lin-39 protein 0 ultrabithorax protein IM Animal Caenorhabditis elegans embryology genetics Comparative Study DNA-Binding Proteins genetics Drosophila Proteins genetics Drosophila melanogaster embryology genetics Evolution, Molecular Gene Expression Regulation, Developmental Homeodomain Proteins genetics Phylogeny Promoter Regions (Genetics) Support, Non-U.S. Gov't Trans-Activators genetics Transcription Factors genetics 108 FBrf0086888 96218895 8626025 1996 06 26 1996 06 26 2002 11 01

0012-1606 175 2 1996 May 1 The activity of D-raf in torso signal transduction is altered by serine substitution, N-terminal deletion, and membrane targeting. 191-204 The Raf family of serine/threonine kinases are essential components in many receptor tyrosine kinase-mediated signal transduction pathways. Here, we analyze the function of D-raf in the Torso (Tor) pathway required to specify cellular fates at the embryonic poles. Using mutant embryos lacking endogenous D-raf protein, we show that D-raf's serine/threonine kinase activity is essential for its role in Tor signal transduction and that human Raf-1 will substitute for D-raf in this pathway. After Tor activation, D-raf becomes hyperphosphorylated. We identified two putative serine phosphorylation sites (S388 and S743) in SF9 cells and demonstrate that S743 or its phosphorylation is essential for D-raf function in embryos. Alanine substitution at S388, N-terminal truncation, or targeted membrane association permits transmission of the Torso signal by D-raf, but these D-raf molecules differ in their rescuing potential and relative biological activity. Membrane-targeted D-raftor4021 showed the highest level of activity, followed by alanine-substituted D-rafS388A and N-terminal-truncated D-raf delta 445. Since the activity profiles for these altered forms of D-raf are distinct, these findings indicate that each structural modification differentially affects the regulation and/or propagation of the Tor signal by these mutant D-raf proteins. Department of Zoology and Genetics, Iowa State University, Ames 50011, USA. Baek K H KH Fabian J R JR Sprenger F F Morrison D K DK Ambrosio L L eng N01-C0-46000 PHS Journal Article

UNITED STATES Dev Biol 0372762 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 Recombinant Proteins 56-41-7 Alanine 56-45-1 Serine EC 2.7.1.- TOR protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Alanine Animal Base Sequence Comparative Study Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Gene Expression Regulation, Developmental Human Membrane Proteins physiology Molecular Sequence Data Morphogenesis genetics Mutagenesis, Site-Directed Nucleopolyhedrovirus genetics Phosphorylation Protein Processing, Post-Translational Protein-Serine-Threonine Kinases genetics physiology Proto-Oncogene Proteins genetics physiology Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases physiology Recombinant Proteins biosynthesis Sequence Deletion Serine Signal Transduction genetics Spodoptera Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0057924 93251920 8486075 1993 06 10 1993 06 10 2000 12 18

0009-5915 102 4 1993 Mar Transcriptional regulation in Drosophila during heat shock: a nuclear run-on analysis. 233-48 We used a nuclear run-on assay as a novel approach to study the changes in transcriptional activity that take place in Drosophila melanogaster during heat shock. In response to a rapid temperature upshift, total transcriptional activity in cultured KC161 cells decreased proportionally to the severity of the shock. After extended stress at 37 degrees C (15 min or more), transcription was severely reduced, and at 39 degrees C most transcription was instantaneously arrested. However, strikingly different responses were observed for individual genes. Transcription of histone H1 genes was severely inhibited even under mild heat shock conditions. Transcription of the actin 5C gene decreased progressively with increasing temperature, while transcription of the core histone genes or of the heat shock cognate genes was repressed only under severe heat shock conditions. Transcriptional activation of the D. melanogaster heat shock genes was also investigated. In unshocked cells, hsp84 was moderately transcribed, while transcriptional activity at the other protein-coding heat shock genes was undetectable (less than 0.2 polymerases per gene). Engaged but paused RNA polymerase molecules were found at the hsp70 and hsp26 genes, but not at the other heat shock genes. The rates of transcription increased with increasing temperature with a peak of expression at around 35 degrees C. At 37 degrees C, induction was less efficient, and no induction was achieved after a rapid shift to 39 degrees C. Increased transcription of the heat shock genes was observed within 1-2 min of heat shock, and maximal rates were reached within 2-5 min. Despite very similar profiles of response, different heat shock genes were transcribed at strikingly different rates, which varied over a 20-fold range. The noncoding heat shock locus 93D was transcribed at a very high rate under non-heat shock conditions, and showed a transcriptional response to elevated temperatures different from that of protein-coding heat shock genes. An estimation of the absolute rates of transcription at different temperatures was obtained. Département de Biologie Moléculaire, Université de Genève, Switzerland. Vazquez J J Pauli D D Tissières A A eng Journal Article

GERMANY Chromosoma 2985138R 0 Heat-Shock Proteins 0 Histones EC 2.7.7.- RNA Polymerase I EC 2.7.7.- RNA Polymerase II IM hsc4 hsp Animal Chromosome Mapping Drosophila melanogaster genetics metabolism Gene Expression Regulation Genetic Techniques Heat adverse effects Heat-Shock Proteins genetics Histones genetics Kinetics Promoter Regions (Genetics) RNA Polymerase I metabolism RNA Polymerase II metabolism Stress genetics Support, Non-U.S. Gov't Transcription, Genetic FBrf0089631 97223508 8812111 1997 04 14 1997 04 14 2003 02 03

0012-1606 178 1 1996 Aug 25 Tosca: a Drosophila gene encoding a nuclease specifically expressed in the female germline. 90-100 We describe here a Drosophila gene, tosca (tos), that is specifically expressed in the female germline. tos mRNA accumulates selectively within the pro-oocyte in germarial region 2 and persists throughout oogenesis. In the early embryo, the maternally supplied tos mRNA is evenly distributed at the syncytial blastoderm stage, but is excluded from the forming cells when cellularization begins. tos product is the first Drosophila member of the RAD2 protein family, a group of related DNA repair nucleases conserved from yeast to humans. Within the family, Tos is more closely related to ExoI, a Schizosaccharomyces pombe 5'-->3' double-stranded DNA exonuclease specifically induced in meiotic prophase I. The definite oocyte localization of tos transcript during meiosis and its ubiquitous distribution in early embryos suggest that tos may play a role in mismatch repair during genetic recombination and early cleavage divisions. Istituto di Biochimica delle Proteine ed Enzimologia, CNR, Naples, Italy. Digilio F A FA Pannuti A A Lucchesi J C JC Furia M M Polito L C LC eng GENBANK X89021 X89022 GM15691 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 0 Fungal Proteins 0 RNA, Messenger 103371-12-6 RAD2 protein, S cerevisiae EC 3.1.- Endodeoxyribonucleases IM Amino Acid Sequence Animal Base Sequence Cloning, Molecular Drosophila melanogaster embryology enzymology genetics Endodeoxyribonucleases genetics Female Fungal Proteins genetics Gene Expression Regulation, Developmental Genes, Insect genetics Molecular Sequence Data Mutation Oogenesis Ovary chemistry Ovum chemistry physiology RNA, Messenger analysis Restriction Mapping Sequence Analysis, DNA Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0089138 96391171 8798144 1997 02 05 1997 02 05 2000 12 18

0925-4773 56 1-2 1996 May Targets of glass regulation in the Drosophila eye disc. 17-24 The Drosophila glass gene is required for the differentiation and survival of photoreceptors in the compound eye, ocelli and larval photoreceptor organ, glass encodes a zinc finger protein which can activate transcription in cell culture and is likely to act by regulating the expression of other genes. We have shown that it directly or indirectly controls the expression of approximately 25% of all enhancer trap lines expressed in the eye disc. glass gene activity is required to activate 19% of the lines, some of which express beta-galactosidase in photoreceptor subtype-specific patterns, and to repress 6%. The phenotype of eye discs doubly mutant for glass and the homeobox gene rough suggests that glass is required for subtype specification and for recruitment of cells to the ommatidial cluster. MCB and HHMI, UC Berkeley, CA 94720, USA. Treisman J E JE Rubin G M GM eng GM33135 GM NIGMS Journal Article

IRELAND Mech Dev 9101218 0 DNA-Binding Proteins 0 Transcription Factors 0 glass protein 0 rough protein IM Animal DNA-Binding Proteins physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian growth & development Enhancer Elements (Genetics) Eye embryology Gene Expression Regulation, Developmental Phenotype Photoreceptors physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors physiology FBrf0145175 21822655 11832221 2002 02 08 2002 03 05 2003 09 09

0896-6273 33 3 2002 Jan 31 Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization. 321-4 The Notch signaling pathway plays a role in cell fate specification in many metazoans. A critical aspect of Notch activation involves proteolysis of the Notch receptor. This cleavage event requires Presenilin as a component of a large multiprotein complex, gamma-secretase. This complex mediates a similar cleavage event of the beta-amyloid precursor protein (APP). The transmembrane protein Nicastrin has been found to associate with Presenilin, Notch, and APP. Recent biochemical and genetic studies have focused on elucidating the function of this protein. Department of Pharmacology and Molecular Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. kopan@pcg.wustl.edu Kopan Raphael R Goate Alison A eng Journal Article Review Review, Tutorial

United States Neuron 8809320 0 Helminth Proteins 0 Membrane Glycoproteins 0 Membrane Proteins 0 PSEN1 protein, human 0 Trans-Activators 0 aph-2 protein, C elegans 0 nicastrin protein 0 notch protein EC 3.4.- Endopeptidases EC 3.4.23 Aspartic Endopeptidases EC 3.4.99.- secretase IM Alzheimer Disease genetics Animal Aspartic Endopeptidases metabolism Drosophila melanogaster physiology Endopeptidases metabolism Helminth Proteins metabolism Human Membrane Glycoproteins metabolism Membrane Proteins metabolism Models, Biological Signal Transduction physiology Trans-Activators metabolism 20 FBrf0090588 97064966 8908516 1997 02 12 1997 02 12 2000 12 18

1088-9051 6 10 1996 Oct Site-selected mutagenesis of the Drosophila second chromosome via plasmid rescue of lethal P-element insertions. 972-9 This paper describes a fast and efficient approach to correlating cloned genes with mutant phenotypes in Drosophila. We make use of a large collection D. melanogaster lines with recessive lethal insertions of a P[lacW] transposon on their second chromosome. Within this collection there clearly must be many insertions corresponding to Drosophila genes that have been cloned and characterized, e.g., via homology with cloned mammalian genes, but for which mutant phenotypes have yet to be identified. We have made use of the fact that P[lacW] contains a plasmid replicon to establish a collection of rescued plasmids containing genomic DNA flanking the sites of transposon insertion. Plasmids representing a total of 1836 lines were independently rescued and pooled in batches of 10 and 100. Pools of 100 plasmids were screened by hybridization with cDNAs corresponding to cloned second chromosome loci. Hybridizing pools were then narrowed down to single plasmids by a process of subdivision and rehybridization, and corresponding mutant lines were obtained. The success rate was better than one in four. This rate would undoubtedly be improved by the use of genomic DNA probes. Guo Y Y Gillan A A Török T T Kiss I I Dow J A JA Kaiser K K eng GENBANK L14270 U59147 X16969 X55199 X77936 Z26918 Z46891 Letter

UNITED STATES Genome Res 9518021 0 DNA Transposable Elements 0 DNA, Recombinant 0 Plasmids IM Animal DNA Transposable Elements DNA, Recombinant Drosophila melanogaster genetics Molecular Sequence Data Mutagenesis, Site-Directed Plasmids Support, Non-U.S. Gov't FBrf0155706 22354101 12466193 2002 12 05 2003 03 10 2003 06 16

0950-1991 130 2 2003 Jan Grainy head controls apical membrane growth and tube elongation in response to Branchless/FGF signalling. 249-58 Epithelial organogenesis involves concerted movements and growth of distinct subcellular compartments. We show that apical membrane enlargement is critical for lumenal elongation of the Drosophila airways, and is independently controlled by the transcription factor Grainy head. Apical membrane overgrowth in grainy head mutants generates branches that are too long and tortuous without affecting epithelial integrity, whereas Grainy head overexpression limits lumenal growth. The chemoattractant Branchless/FGF induces tube outgrowth, and we find that it upregulates Grainy head activity post-translationally, thereby controlling apical membrane expansion to attain its key role in branching. We favour a two-step model for FGF in branching: first, induction of cell movement and apical membrane growth, and second, activation of Grainy head to limit lumen elongation, ensuring that branches reach and attain their characteristic lengths. Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden. Hemphälä Johanna J Uv Anne A Cantera Rafael R Bray Sarah S Samakovlis Christos C eng Journal Article

England Development 8701744 0 Antigens, CD95 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Insect Proteins 0 Transcription Factors 0 branchless protein, Drosophila 0 transcription factor NTF-1 62031-54-3 Fibroblast Growth Factors IM Animal Antigens, CD95 metabolism Cell Membrane metabolism Cell Polarity Cell Size DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster physiology Epithelium growth & development Fibroblast Growth Factors metabolism Genes, Reporter Immunohistochemistry Insect Proteins metabolism Microscopy, Electron Morphogenesis Signal Transduction Support, Non-U.S. Gov't Trachea anatomy & histology growth & development Transcription Factors genetics metabolism FBrf0155521 22399936 12511959 2003 01 03 2003 01 30

0028-0836 421 6918 2003 Jan 2 Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity. 83-7 Two prominent characteristics of epithelial cells, apical-basal polarity and a highly ordered cytoskeleton, depend on the existence of precisely localized protein complexes associated with the apical plasma membrane, and on a separate machinery that regulates the spatial order of actin assembly. ERM (ezrin, radixin, moesin) proteins have been proposed to link transmembrane proteins to the actin cytoskeleton in the apical domain, suggesting a structural role in epithelial cells, and they have been implicated in signalling pathways. Here, we show that the sole Drosophila ERM protein Moesin functions to promote cortical actin assembly and apical-basal polarity. As a result, cells lacking Moesin lose epithelial characteristics and adopt invasive migratory behaviour. Our data demonstrate that Moesin facilitates epithelial morphology not by providing an essential structural function, but rather by antagonizing activity of the small GTPase Rho. Thus, Moesin functions in maintaining epithelial integrity by regulating cell-signalling events that affect actin organization and polarity. Furthermore, our results show that there is negative feedback between ERM activation and activity of the Rho pathway. DCMB Group, Department of Biology, Duke University, Box 91000, Durham, North Carolina 27708, USA. Speck Olga O Hughes Sarah C SC Noren Nicole K NK Kulikauskas Rima M RM Fehon Richard G RG eng GENBANK L38909 Journal Article

England Nature 0410462 0 Actins 0 Microfilament Proteins 0 Phosphoproteins 0 ezrin 107898-34-0 RHO1 protein 144131-77-1 moesin EC 3.6.1.- rho GTP-Binding Proteins IM Actins metabolism Animal Animals, Genetically Modified Cell Line Cell Movement Cell Polarity Cell Size Drosophila melanogaster cytology genetics metabolism Epithelial Cells cytology metabolism Feedback, Biochemical Microfilament Proteins genetics metabolism Molecular Sequence Data Mutation Phenotype Phosphoproteins genetics metabolism Signal Transduction Support, U.S. Gov't, P.H.S. Swine rho GTP-Binding Proteins genetics metabolism FBrf0053997 92008631 1915852 1991 10 28 1991 10 28 2000 12 18

0014-5793 289 2 1991 Sep 9 Identification of seven novel protein-tyrosine kinase genes of Drosophila by the polymerase chain reaction. 235-8 We used the polymerase chain reaction to identify 7 novel tyrosine-kinase genes (dtk1 to -7) in Drosophila melanogaster, dtk4 coded for a part of the kinase catalytic domain nearly identical in sequence to that of the human receptor for insulin-like growth factor 1, whereas sequences encoded by dtk1 and dtk2 were highly homologous to that of the chicken fibroblast growth factor receptor. Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan. Shishido E E Emori Y Y Saigo K K eng GENBANK S55969 S55971 S55973 S55975 S55977 S55979 S55982 X58801 X58802 X58803 Journal Article

NETHERLANDS FEBS Lett 0155157 0 Deoxyribonucleotides 0 Oligonucleotide Probes 9007-49-2 DNA EC 2.7.1.112 Protein-Tyrosine Kinase IM dtk1 dtk2 dtk3 dtk4 dtk5 dtk6 dtk7 Alleles Amino Acid Sequence Animal Base Sequence Comparative Study DNA genetics Deoxyribonucleotides Drosophila enzymology genetics Genes, Structural Molecular Sequence Data Oligonucleotide Probes Polymerase Chain Reaction methods Protein-Tyrosine Kinase genetics Restriction Mapping Sequence Homology, Nucleic Acid FBrf0089755 96293357 8698811 1996 09 03 1996 09 03 2002 11 01

0021-9525 134 1 1996 Jul armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila. 149-63 Cellularization of the Drosophila embryo results in the formation of a cell monolayer with many characteristics of a polarized epithelium. We have used antibodies specific to cellular junctions and nascent plasma membranes to study the formation of the zonula adherens (ZA) in relation to the establishment of basolateral membrane polarity. The same approach was then used as a test system to identify X-linked zygotically active genes required for ZA formation. We show that ZA formation begins during cellularization and that the basolateral membrane domain is established at mid-gastrulation. By creating deficiencies for defined regions of the X chromosome, we have identified genes that are required for the formation of the ZA and the generation of basolateral membrane polarity. We show that embryos mutant for both stardust (sdt) and bazooka (baz) fail to form a ZA. In addition to the failure to establish the ZA, the formation of the monolayered epithelium is disrupted after cellularization, resulting in formation of a multilayered cell sheet by mid-gastrulation. SEM analysis of mutant embryos revealed a conversion of cells exhibiting epithelial characteristics into cells exhibiting mesenchymal characteristics. To investigate how mutations that affect an integral component of the ZA itself influence ZA formation, we examined embryos with reduced maternal and zygotic supply of wild-type Arm protein. These embryos, like embryos mutant for both sdt and baz, exhibit an early disruption of ZA formation. These results suggest that early stages in the assembly of the ZA are critical for the stability of the polarized blastoderm epithelium. Department of Molecular Biology, Princeton University, Princeton, New Jersey 08540, USA. Müller H A HA Wieschaus E E eng 5R01HD22780 HD NICHD Journal Article

UNITED STATES J Cell Biol 0375356 0 Membrane Glycoproteins 0 Proteins 0 armadillo protein, Drosophila 0 neurotactin IM Animal Blastoderm cytology Cell Adhesion Cell Polarity Chromosome Mapping Drosophila melanogaster embryology genetics Epithelial Cells Fluorescent Antibody Technique, Indirect Gastrula cytology Gene Expression Regulation, Developmental Genes, Structural, Insect Intercellular Junctions ultrastructure Membrane Glycoproteins metabolism Proteins physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. X Chromosome FBrf0127184 20183606 10716925 2000 04 27 2000 04 27 2000 12 18

0261-4189 19 6 2000 Mar 15 Hsp90 is a core centrosomal component and is required at different stages of the centrosome cycle in Drosophila and vertebrates. 1252-62 To determine the molecular composition of the centrosome of a higher eukaryote, we carried out a systematic nano-electrospray tandem or MALDI mass spectrometry analysis of the polypeptides present in highly enriched preparations of immunoisolated Drosophila centrosomes. One of the proteins identified is Hsp83, a member of the highly conserved Hsp90 family including chaperones known to maintain the activity of many proteins but suspected to have other essential, unidentified functions. We have found that a fraction of the total Hsp90 pool is localized at the centrosome throughout the cell cycle at different stages of development in Drosophila and vertebrates. This association between Hsp90 and the centrosome can be observed in purified centrosomes and after treatment with microtubule depolymerizing drugs, two criteria normally used to define core centrosomal components. Disruption of Hsp90 function by mutations in the Drosophila gene or treatment of mammalian cells with the Hsp90 inhibitor geldanamycin, results in abnormal centrosome separation and maturation, aberrant spindles and impaired chromosome segregation. This suggests that another role of Hsp90 might be to ensure proper centrosome function. Cell Biology and Cell Biophysics Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Lange B M BM Bachi A A Wilm M M González C C eng Journal Article

ENGLAND EMBO J 8208664 0 Antibodies 0 Heat-Shock Proteins 90 0 Quinones 30562-34-6 geldanamycin IM Adsorption Animal Antibodies immunology Brain cytology drug effects growth & development metabolism Cell Cycle drug effects Cell Line Centrioles chemistry drug effects Centrosome chemistry drug effects immunology Chromosome Segregation drug effects physiology Drosophila melanogaster cytology drug effects embryology growth & development Fluorescent Antibody Technique Heat-Shock Proteins 90 antagonists & inhibitors genetics metabolism Human Larva cytology drug effects genetics growth & development Mitosis drug effects Mitotic Spindle Apparatus drug effects physiology Mutation genetics Quinones pharmacology Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Support, Non-U.S. Gov't Vertebrates FBrf0058921 93147941 8426233 1993 03 04 1993 03 04 2000 12 18

0270-6474 13 2 1993 Feb Growth cone choices of Drosophila motoneurons in response to muscle fiber mismatch. 714-32 In Drosophila embryos, each motoneuron is accurately matched to one or more singly identifiable muscle fibers. In this article we altered the number and pattern of the embryonic muscle fibers using genetic, heat shock, and laser ablation methods to test whether motoneuron growth cones are able to recognize specific targets. The choices made by two motoneurons were assayed using both intracellular dye fills and immunocytochemistry. The motoneurons RP1 and RP3 have nearly identical central and peripheral axonal trajectories. However, RP3 innervates the two most ventral longitudinal muscle fibers, 7 and 6, while RP1 grows past these fibers to innervate only muscle fiber 13. In rhomboid mutants muscle fiber 7 does not develop. Despite the loss of one of its targets, RP3 faithfully innervated the remaining muscle fiber 6 in over 80% of the observed cases. Furthermore, neuron RP1 accurately innervated muscle fiber 13, although it traversed one fiber fewer to reach it. Laser ablation of muscle fiber 7 confirmed the target choices shown by the motoneurons. In numb mutants, multiple muscle fibers, including 7, 13, and 12, fail to develop. This allowed us to test whether fibers distal to the target are involved in muscle fiber recognition, possibly by halting the growth cone advance. In mutant embryos, RP3 innervated muscle fiber 6 at the same frequency regardless of the absence of the distal muscle fiber 13. By contrast, RP1, which had lost its target entirely, frequently failed to innervate any muscle fiber during the period examined. Finally, muscle fiber 13 can be duplicated in wild-type embryos by means of a brief heat pulse during myogenesis. Presented with two targets, RP1 innervated both fibers in each case examined, while RP3 synapsed with muscle fibers 7 and 6 normally. Neuron-specific antibodies revealed that the embryonic growth cone choices were not transient, but persisted into the larval neuromuscular projections. These results indicate that each motoneuron growth cone has a primary target preference, which is retained even when the numbers of the muscle fibers, and therefore their relative positions, are altered. We therefore suggest that synaptic recognition by Drosophila motoneuron growth cones relies on unique features of the individual muscle fibers. Department of Biology, Yale University, New Haven, Connecticut 06511. Chiba A A Hing H H Cash S S Keshishian H H eng Journal Article

UNITED STATES J Neurosci 8102140 0 Antibodies, Monoclonal IM Animal Antibodies, Monoclonal Axons physiology ultrastructure Cell Differentiation Drosophila melanogaster embryology genetics Heat Immunohistochemistry Lasers Motor Neurons physiology ultrastructure Muscles cytology embryology innervation Mutation Neuromuscular Junction ultrastructure Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0073018 94240181 8183953 1994 06 16 1994 06 16 2000 12 18

0027-8424 91 10 1994 May 10 Identification of Drosophila cytoskeletal proteins by induction of abnormal cell shape in fission yeast. 4589-93 To clone metazoan genes encoding regulators of cell shape, we have developed a functional assay for proteins that affect the morphology of a simple organism, the fission yeast Schizosaccharomyces pombe. A Drosophila melanogaster cDNA library was constructed in an inducible expression vector and transformed into S. pombe. When expression of the Drosophila sequences was induced, aberrant cell shapes were found in 0.2% of the transformed colonies. Four severe phenotypes representing defects in cytokinesis and/or cell shape maintenance were examined further. Each displayed drastic and specific reorganizations of the actin cytoskeleton. Three of the cDNAs responsible for these defects appear to encode cytoskeletal components: the actin binding proteins profilin and cofilin/actin depolymerizing factor and a membrane-cytoskeleton linker of the ezrin/merlin family. These results demonstrate that a yeast phenotypic screen efficiently identifies conserved genes from more complex organisms and sheds light on their potential in vivo functions. Department of Cell Biology, Duke University Medical Center, Durham, NC 27710. Edwards K A KA Montague R A RA Shepard S S Edgar B A BA Erikson R L RL Kiehart D P DP eng GENBANK U08217 U08218 GM33830 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Cytoskeletal Proteins 0 Genetic Vectors 0 Microfilament Proteins 0 Nerve Tissue Proteins 0 cofilin IM Amino Acid Sequence Animal Cloning, Molecular methods Comparative Study Conserved Sequence Cytoskeletal Proteins biosynthesis genetics physiology Drosophila melanogaster genetics physiology Gene Library Genetic Vectors Human Microfilament Proteins biosynthesis genetics physiology Molecular Sequence Data Nerve Tissue Proteins biosynthesis genetics physiology Schizosaccharomyces genetics Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Vertebrates FBrf0079169 95113174 7529201 1995 02 09 1995 02 09 2002 11 01

0012-1606 166 2 1994 Dec Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase. 543-56 The Drosophila segment polarity gene product Armadillo provides a link between two seemingly separate processes, regulation of segmental pattern by the Wingless intercellular signal and the function of cell-cell adherens junctions. armadillo was originally identified because of its segment polarity phenotype but subsequently was found to be the homolog of the vertebrate adherens junction protein beta-catenin. We examined the nature of the post-translational modification of Armadillo and its possible role in regulating Armadillo function. Armadillo is a phosphoprotein. Its level of phosphorylation varies both during embryonic development and from tissue to tissue. Phosphorylation occurs on both serine or threonine and tyrosine residues. Finally, Wingless signal negatively regulates Armadillo phosphorylation, while the segment polarity gene product Zeste-white 3, a serine/threonine protein kinase, promotes Armadillo phosphorylation. We discuss the implications of these results for regulation of Wingless/Wnt-1 signaling and adherens junction function. Department of Biology, University of North Carolina at Chapel Hill 27599. Peifer M M Pai L M LM Casey M M eng GM47857 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 0 Proteins 0 Proto-Oncogene Proteins 0 armadillo protein, Drosophila 117758-26-6 wingless protein, Drosophila 17885-08-4 Phosphoserine 21820-51-9 Phosphotyrosine 55520-40-6 Tyrosine EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 shaggy kinase, Drosophila IM arm wg zw3 Amino Acid Sequence Animal Cell Adhesion Comparative Study Consensus Sequence Drosophila melanogaster Molecular Sequence Data Phosphorylation Phosphoserine metabolism Phosphotyrosine Protein Kinases metabolism Protein-Serine-Threonine Kinases physiology Proteins physiology Proto-Oncogene Proteins metabolism Sequence Alignment Sequence Homology, Amino Acid Signal Transduction Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tyrosine analogs & derivatives metabolism FBrf0108570 99265936 10331974 1999 07 22 1999 07 22 2002 10 21

0950-1991 126 12 1999 Jun Hedgehog activates the EGF receptor pathway during Drosophila head development. 2623-30 The Hedgehog (Hh) and Epidermal growth factor receptor (EGFR) signaling pathways play critical roles in pattern formation and cell proliferation in invertebrates and vertebrates. In this study, we demonstrate a direct link between these two pathways in Drosophila melanogaster. Hh and EGFR signaling are each required for the formation of a specific region of the head of the adult fruitfly. We show that hh and vein (vn), which encodes a ligand of the Drosophila EGFR (Schnepp, B., Grumbling, G., Donaldson, T. and Simcox, A. (1996) Genes Dev. 10, 2302-13), are expressed in adjacent domains within the imaginal primordium of this region. Using loss- and gain-of-function approaches, we demonstrate that Hh activates vn expression. We also show that Hh activation of vn is mediated through the gene cubitus interruptus (ci) and that this activation requires the C-terminal region of the Ci protein. Finally, we demonstrate that wingless (wg) represses vn expression, thereby limiting the domain of EGFR signaling. Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6074, USA. Amin A A Li Y Y Finkelstein R R eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 cubitus interruptus protein 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila 182299-68-9 vein protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal DNA-Binding Proteins genetics metabolism Drosophila genetics growth & development Gene Expression Regulation, Developmental Head growth & development physiology Insect Proteins genetics metabolism Mutation Proto-Oncogene Proteins genetics metabolism Receptor, Epidermal Growth Factor metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription Factors genetics metabolism FBrf0087716 96218905 8626035 1996 06 26 1996 06 26 2003 06 16

0012-1606 175 2 1996 May 1 Regulation of two pair-rule stripes by a single enhancer in the Drosophila embryo. 314-24 Previous studies on the regulation of the segmentation gene even-skipped (eve) have centered on the transcription of stripe 2. Here, we characterize another enhancer module contained within the complex eve promoter that directs expression of stripes 3 and 7. This enhancer is approximately 500 bp in length and maps approximately 3.3 kb upstream of the transcription start site. The stripe 3 + 7 enhancer appears to be regulated by one or more ubiquitously distributed activators, including components of a JAK-Stat pathway. The two-stripe pattern results via multiple tiers of repressors which delimit this ubiquitous activation. The zinc finger repressor hunchback appears to be responsible for establishing the anterior border of stripe 3 and the posterior border of stripe 7. knirps, a member of the nuclear receptor family of transcription factors, appears to establish the posterior border of stripe 3 and the anterior border of stripe 7. Activator and repressor proteins bind in vitro to several sites within the enhancer. These findings suggest a general model for the regulation of segmentation stripes, whereby enhancers integrate positional information provided by broadly distributed activators and spatially restricted repressors. Department of Biology, New York University, New York 10003, USA. Small S S Blair A A Levine M M eng GENBANK S81995 GM34431 GM NIGMS GM51946 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 0 DNA-Binding Proteins 0 ESPD protein, E coli 0 Homeodomain Proteins 0 KNI protein 0 Repressor Proteins 0 Transcription Factors 0 hunchback protein, Drosophila 108911-13-3 even-skipped protein, Drosophila IM Alleles Animal Animals, Genetically Modified Base Sequence DNA-Binding Proteins physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Enhancer Elements (Genetics) Gene Expression Regulation, Developmental Genes, Structural, Insect Homeodomain Proteins genetics physiology Molecular Sequence Data Morphogenesis genetics Repressor Proteins physiology Sequence Alignment Support, U.S. Gov't, P.H.S. Transcription Factors physiology Transcription, Genetic Transgenes Zygote metabolism FBrf0088355 96257214 8666267 1996 08 08 1996 08 08 2003 09 17

0378-1119 171 2 1996 Jun 1 Identification of a novel Drosophila melanogaster heat-shock gene, lethal(2)denticleless [l(2)dtl], coding for an 83-kDa protein. 163-70 In this study, we describe the identification of a novel Drosophila melanogaster (Dm) gene, l(2)dtl, characterized by elevated expression under heat-shock (HS) conditions. It encodes a protein of 83 kDa with no homology to known members of the HSP90 family and other proteins. Gene l(2)dtl is located on the right arm of the second chromosome at locus 59F5, close to the tumor suppressor gene l(2)tid, a homolog of the dnaJ encoding a chaperone strongly conserved in evolution. In the following, we present the sequence of l(2)dtl, the putative protein it encodes, and its molecular localization in a closely interspaced gene cluster consisting of at least four nested genes spanning an approximately 10-kb genomic interval. Furthermore, we present the temporal expression of l(2)dtl in the wild type under normal and HS conditions, and describe the isolation and the phenotype of eight embryonic lethal l(2)dtl mutants. Institut für Genetik, Johannes Gutenberg-Universität, Mainz, Germany. Kurzik@mzdmza.zdv.uni-mainz.de Kurzik-Dumke U U Neubauer M M Debes A A eng GENBANK X83414 Journal Article

NETHERLANDS Gene 7706761 0 Heat-Shock Proteins 0 l(2)dtl protein, Drosophila IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping Drosophila melanogaster embryology genetics Embryo, Nonmammalian pathology Genes, Lethal Heat-Shock Proteins biosynthesis chemistry genetics Heat-Shock Response Molecular Sequence Data Mutation Sequence Analysis, DNA Support, Non-U.S. Gov't FBrf0036519 82211747 6806142 1982 08 26 1982 08 26 2000 12 18

0016-6731 99 3-4 1981 Nov-Dec Interactions between sex-transformation mutants of Drosophila melanogaster. I. Hemolymph vitellogenins and gonad morphology. 429-41 In Drosophila, vitellogenins (yolk protein precursors) are synthesized by the female fat body, secreted into the hemolymph and subsequently taken up by the developing oocytes. The male fat body, on the other hand, does not do this even when immature ovaries are transplanted into the body cavity and grow. Thus, the hemolymph vitellogenins serve as an easily detectable sexually dimorphic biochemical marker.--We have examined hemolymph vitellogenins by SDS polyacrylamide gel electrophoresis in flies carrying various sex-transformation mutants (dsx, tra, tra-2 and tra-2OTF) singly and in all possible combinations. Chromosomal females homozygous for tra or tra-2 have no detectable hemolymph vitellogenins, while those homozygous for tra-2OTF exhibit appreciable levels of these proteins. Flies homozygous for dsx, both X/X and X/Y, have hemolymph vitellogenins, although the amount is consistently smaller in the latter. Indeed, X/Y; dsx/dsx is the only genotype in which hemolymph vitellogenins are detected in the X/Y flies. A clear hierarchy of epistasis exists among these sex-transformation mutants when they are examined in various combinations: dsx greater than tra, tra-2 greater than tra-2OTF. Moreover, an interaction between tra-2OTF and tra was seen in these experiments: X/X; tra-2OTF/tra-2OTF flies show the presence of only a trace of hemolymph vitellogenins when they are made heterozygous for tra. These results, combined with observations on gonad morphology, are discussed with respect to the Baker and Ridge (1980) hypothesis of sex determination. Ota T T Fukunaga A A Kawabe M M Oishi K K eng Journal Article

UNITED STATES Genetics 0374636 0 Lipoproteins 0 Vitellogenin IM Animal Drosophila melanogaster genetics Female Genotype Gonads anatomy & histology Hemolymph analysis Lipoproteins biosynthesis Male Mutation Phenotype Sex Determination (Analysis) Sex Differentiation Vitellogenin biosynthesis X Chromosome FBrf0152246 22194791 12198495 2002 09 02 2002 10 11 2002 11 05

1465-7392 4 9 2002 Sep Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. 705-10 Although Jun amino-terminal kinase (JNK) is known to mediate a physiological stress signal that leads to cell death, the exact role of the JNK pathway in the mechanisms underlying intrinsic cell death is largely unknown. Here we show through a genetic screen that a mutant of Drosophila melanogaster tumour-necrosis factor receptor-associated factor 1 (DTRAF1) is a dominant suppressor of Reaper-induced cell death. We show that Reaper modulates the JNK pathway through Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), which negatively regulates DTRAF1 by proteasome-mediated degradation. Reduction of JNK signals rescues the Reaper-induced small eye phenotype, and overexpression of DTRAF1 activates the Drosophila ASK1 (apoptosis signal-regulating kinase 1; a mitogen-activated protein kinase kinase kinase) and JNK pathway, thereby inducing cell death. Overexpresson of DIAP1 facilitates degradation of DTRAF1 in a ubiquitin-dependent manner and simultaneously inhibits activation of JNK. Expression of Reaper leads to a loss of DIAP1 inhibition of DTRAF1-mediated JNK activation in Drosophila cells. Taken together, our results indicate that DIAP1 may modulate cell death by regulating JNK activation through a ubiquitin#150;proteasome pathway. Laboratory for Cell Recovery Mechanisms, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Kuranaga Erina E Kanuka Hirotaka H Igaki Tatsushi T Sawamoto Kazunobu K Ichijo Hidenori H Okano Hideyuki H Miura Masayuki M eng GENBANK AB038236 Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Peptides 0 Proteins 0 TNF receptor-associated factor 1 0 inhibitor of apoptosis 1, Drosophila 0 reaper peptide, Drosophila EC 2.7.1.37 MAP Kinase Kinase Kinases EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- MAPK kinase kinase 5 EC 2.7.10.- c-Jun amino-terminal kinase IM Animal Animals, Genetically Modified Apoptosis Base Sequence Drosophila Proteins genetics metabolism Drosophila melanogaster genetics growth & development metabolism Enzyme Activation Eye growth & development Genes, Insect MAP Kinase Kinase Kinases genetics metabolism Mitogen-Activated Protein Kinases metabolism Molecular Sequence Data Mutation Peptides genetics metabolism Phenotype Proteins metabolism Support, Non-U.S. Gov't FBrf0160771 22719037 12835385 2003 07 01 2003 09 30

0950-1991 130 16 2003 Aug Differential expression of the Drosophila BX-C in polytene chromosomes in cells of larval fat bodies: a cytological approach to identifying in vivo targets of the homeotic Ubx, Abd-A and Abd-B proteins. 3683-9 We have analyzed the expression of homeotic Bithorax Complex proteins in the fat bodies of Drosophila larvae by staining with specific antibodies. We have found that these proteins are differentially expressed along the anteroposterior (AP) axis of the fat body, with patterns parallel to those previously characterized for the larval and adult epidermis. As fat body nuclei have polytene chromosomes, we were able to identify the BX-C locus and show that it assumes a strongly puffed conformation in cells actively expressing the genes of the BX-C. Immunostaining of these polytene chromosomes provided the resolution to cytologically map binding sites of the three proteins: Ubx, Abd-A and Abd-B. The results of this work provide a system with which to study the positioning of chromatin regulatory proteins in either a repressed and/or active BXC at the cytological level. In addition, the results of this work provide a map of homeotic target loci and thus constitute the basis for a systematic identification of genes that are direct in vivo targets of the BX-C genes. Istituto Pasteur, Fondazione Cenci Bolognetti, Dipartimento di Genetica e Biologia Molecolare, Università La Sapienza, 00185 Rome, Italy. Marchetti Marcella M Fanti Laura L Berloco Maria M Pimpinelli Sergio S eng Journal Article

England Development 8701744 0 Abd-B proteins, Drosophila 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Homeodomain Proteins 0 Nuclear Proteins 0 Repressor Proteins 0 Transcription Factors 0 trithorax gene product 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila 134549-01-2 Polycomb protein, insect IM Animal Binding Sites Chromosomes genetics DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics physiology Fat Body cytology physiology Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins genetics metabolism In Situ Hybridization Nuclear Proteins genetics metabolism Protein Binding Repressor Proteins genetics metabolism Transcription Factors genetics metabolism FBrf0093664 97281709 9136017 1997 09 03 1997 09 03 2000 12 18

0016-6731 146 1 1997 May Autosomal mutations affecting adhesion between wing surfaces in Drosophila melanogaster. 275-85 Integrins are evolutionarily conserved transmembrane alpha,beta heterodimeric receptors involved in cell-to-matrix and cell-to-cell adhesions. In Drosophila the position-specific (PS) integrins mediate the formation and maintenance of junctions between muscle and epidermis and between the two epidermal wing surfaces. Besides integrins, other proteins are implicated in integrin-dependent adhesion. In Drosophila, somatic clones of mutations in PS integrin genes disrupt adhesion between wing surfaces to produce wing blisters. To identify other genes whose products function in adhesion between wing surfaces, we conducted a screen for autosomal mutations that produce blisters in somatic wing clones. We isolated 76 independent mutations in 25 complementation groups, 15 of which contain more than one allele. Chromosomal sites were determined by deficiency mapping, and genetic interactions with mutations in the beta PS integrin gene myospheroid were investigated. Mutations in four known genes (blistered, Delta, dumpy and mastermind) were isolated. Mutations were isolated in three new genes (piopio, rhea and steamer duck) that affect myo-epidermal junctions or muscle function in embryos. Mutations in three other genes (kakapo, kiwi and moa) may also affect cell adhesion or muscle function at hatching. These new mutants provide valuable material for the study of integrin-dependent cell-to-cell adhesion. Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA. Prout M M Damania Z Z Soong J J Fristrom D D Fristrom J W JW eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Cell Adhesion genetics Drosophila melanogaster genetics Genes, Lethal Larva Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Wing FBrf0038632 82222193 6806814 1982 08 26 1982 08 26 2000 12 18

0027-8424 79 8 1982 Apr Synapsis-dependent allelic complementation at the decapentaplegic gene complex in Drosophila melanogaster. 2636-40 Allelic complementation at the decapentaplegic gene complex (dpp: 2-4-0, cytogenetic location: polytene chromosome bands 22F1-3) of Drosophila melanogaster frequently occurs between site mutations. Two specific instances of allelic complementation are shown to be dependent upon normal somatic chromosome synapsis of homologous dpp genes. Numerous strains have been identified that bear lesions that disrupt allelic complementation when heterozygous with structurally normal chromosomes; each of these 57 strains contains a gross chromosomal rearrangement with a break on chromosome 2. The properties of the rearrangements carried by 50 of these strains are consonant with the idea that their effects are due to a disruption of somatic chromosome synapsis in the dpp region of chromosome arm 2L. In double heterozygotes of simple two-break rearrangements, allelic complementation is restored (presumably through the restoration of structural homozygosity). The types of rearrangements that disrupt complementation have properties very similar to those of rearrangements that disrupt the transvection effect at bithorax [Lewis, E. B. (1954) Am. Nat. 88, 225-239]. The existence of synapsis-dependent allelic complementation is a demonstration of the physiological importance of nuclear organization in gene expression. Gelbart W M WM eng CA-00588 CA NCI GM-28669 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 IM Alleles Animal Chromosome Mapping Drosophila melanogaster genetics Genes Genetic Complementation Test Heterozygote Mutation Phenotype Support, U.S. Gov't, P.H.S. FBrf0148964 22010061 12015301 2002 05 16 2002 07 22

0950-1991 129 11 2002 Jun Towards a model of the organisation of planar polarity and pattern in the Drosophila abdomen. 2749-60 The abdomen of adult Drosophila consists of a chain of alternating anterior (A) and posterior (P) compartments which are themselves subdivided into stripes of different types of cuticle. Most of the cuticle is decorated with hairs and bristles that point posteriorly, indicating the planar polarity of the cells. Here we research the link between pattern and polarity.Previously we showed that the pattern of the A compartment depends on the local concentration (the scalar) of a Hedgehog morphogen produced by cells in the P compartment. Here we present evidence that the P compartment is patterned by another morphogen, Wingless, which is induced by Hedgehog in A compartment cells and then spreads back into the P compartment. We also find that both Hedgehog and Wingless appear to specify pattern by activating the optomotor blind gene, which encodes a transcription factor.We re-examine our working model that planar polarity is determined by the cells reading the gradient in concentration (the vector) of a morphogen 'X' which is produced on receipt of Hedgehog. We present evidence that Hedgehog induces X production by driving optomotor blind expression. We tried but failed to identify X and present data that X is not likely to operate through the conventional Notch, Decapentaplegic, EGF or FGF transduction pathways, or to encode a Wnt. However, we argue that Wingless may act to enhance the production or organise the distribution of X. A simple model that accommodates our results is that X forms a monotonic gradient extending from the back of the A compartment to the front of the P compartment in the next segment, a unit constituting a parasegment. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. pal@mrc-lmb.cam.ac.uk Lawrence Peter A PA Casal José J Struhl Gary G eng Journal Article

England Development 8701744 IM Abdomen embryology Animal Body Patterning physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Gene Expression Regulation, Developmental Mutagenesis Signal Transduction Support, Non-U.S. Gov't FBrf0082318 95269674 7750456 1995 06 19 1995 06 19 2002 11 01

0013-7227 136 6 1995 Jun Drosophila insulin receptor: lectin-binding properties and a role for oxidation-reduction of receptor thiols in activation. 2357-66 The glycosylation of the Drosophila insulin receptor (DIR) has been compared to that of the rat insulin receptor by examining the binding of receptors to the lectins wheat germ agglutinin, Concanavalin-A, and lentil lectin. Although rat insulin receptors bound and were specifically eluted from all three lectins, only a small fraction of the DIR (< 5%) was retained on wheat germ agglutinin. In contrast, the DIR bound strongly to Concanavalin-A and lentil lectin and was recovered from lentil lectin columns after elution with alpha-methyl-mannoside. The pattern of lectin binding indicates that glycosylation of the DIR and rat insulin receptors differs, with the DIR containing primarily high mannose-type oligosaccharides. After lectin chromatography, the DIR exhibited an elevated level of basal autophosphorylation and kinase activity, which could be restored to a low level by incubation with 0.5 mM dithiothreitol (DTT). DTT did not, however, affect ligand-stimulated kinase activity. The ability of low concentrations of DTT to deactivate the DIR kinase suggests that, like the mammalian receptor, beta-subunit thiols may be involved in regulation of conformational changes between activated and unactivated receptor states. Interestingly, DTT-induced deactivation of the DIR was blocked by preincubation with an antipeptide antibody against the carboxy-terminal domain of the DIR. This suggests that the DIR carboxyl terminus undergoes a conformational change during the activation-inactivation cycle of the kinase, which can be sterically hindered by the antibody. Conformational changes in this region of the mammalian receptor have been observed, and these data suggest that features of the insulin receptor activation mechanism have been substantially conserved during evolution. Department of Anatomy and Cell Biology, State University of New York, Brooklyn 11203, USA. Marin-Hincapie M M Garofalo R S RS eng Journal Article

UNITED STATES Endocrinology 0375040 0 Antibodies 0 Lectins 0 Peptide Fragments 0 Sulfhydryl Compounds 3483-12-3 Dithiothreitol EC 2.7.1.112 Receptor, Insulin AIM IM Amino Acid Sequence Animal Antibodies Comparative Study Dithiothreitol pharmacology Drosophila melanogaster genetics metabolism Glycosylation Lectins metabolism Molecular Sequence Data Oxidation-Reduction Peptide Fragments genetics immunology Phosphorylation Rats Receptor, Insulin chemistry genetics metabolism Sulfhydryl Compounds metabolism Support, U.S. Gov't, Non-P.H.S. FBrf0110096 99339909 10409497 1999 10 08 1999 10 08 2000 12 18

0950-1991 126 16 1999 Aug Wingless, decapentaplegic and EGF receptor signaling pathways interact to specify dorso-ventral pattern in the adult abdomen of Drosophila. 3495-507 Adult abdominal segments of Drosophila are subdivided along the dorso-ventral axis into a dorsal tergite, a ventral sternite and ventro-lateral pleural cuticle. We report that this pattern is largely specified during the pupal stage by Wingless (Wg), Decapentaplegic (Dpp) and Drosophila EGF Receptor (DER) signaling. Expression of wg and dpp is activated at the posterior edge of the anterior compartment by Hedgehog signaling. Within this region, wg and dpp are expressed in domains that are mutually exclusive along the dorso-ventral axis: wg is expressed in the sternite and medio-lateral tergite, whereas dpp expression is confined to the pleura and the dorsal midline. Neither gene is expressed in the lateral tergite. Shirras and Couso (1996, Dev. Biol. 175, 24-36) have shown that tergite and sternite cell fates are specified by Wg signaling. We find that DER acts synergistically with Wg to promote tergite and sternite identities, and that Wg and DER activities are opposed by Dpp signaling, which promotes pleural identity. Wg and Dpp interact antagonistically at two levels. First, their expression is confined to complementary domains by mutual transcriptional repression. Second, Wg and Dpp compete directly with one another by exerting opposite effects on cell fate. DER signaling does not affect the expression of wg or dpp, indicating that it interacts with Wg and Dpp at the level of cell fate determination. Within the tergite, the requirements for Wg and DER function are roughly complementary: Wg is required mainly in the medial region, whereas DER is most important laterally. Finally, we show that Dpp signaling at the dorsal midline controls dorso-ventral patterning within the tergite by promoting pigmentation in the medial region. Department of Biology, Washington University, St Louis, MO 63130, USA. Kopp A A Blackman R K RK Duncan I I eng GM32318 GM NIGMS Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 dpp protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Abdomen Animal Body Patterning physiology Drosophila melanogaster growth & development physiology Gene Expression Regulation, Developmental Insect Proteins genetics physiology Organ Specificity Proto-Oncogene Proteins genetics physiology Pupa Receptor, Epidermal Growth Factor physiology Repressor Proteins physiology Signal Transduction physiology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0130184 20469360 11014821 2000 10 25 2000 11 30 2002 04 19

0016-6731 156 2 2000 Oct The LAMMER protein kinase encoded by the Doa locus of Drosophila is required in both somatic and germline cells and is expressed as both nuclear and cytoplasmic isoforms throughout development. 749-61 Activity of the Darkener of apricot (Doa) locus of Drosophila melanogaster is required for development of the embryonic nervous system, segmentation, photoreceptor maintenance, normal transcription, and sexual differentiation. The gene encodes a protein kinase, with homologues throughout eukaryotes known as the LAMMER kinases. We show here that DOA is expressed as at least two different protein isoforms of 105 and 55 kD throughout development, which are primarily localized to the cytoplasm and nucleus, respectively. Doa transcripts and protein are expressed in all cell types both during embryogenesis and in imaginal discs. Although it was recently shown that DOA kinase is essential for normal sexual differentiation, levels of both kinase isoforms are equal between the sexes during early pupal development. The presence of the kinase on the cell membrane and in the nuclei of polytene salivary gland cells, as well as exclusion from the nuclei of specific cells, may be indicative of regulated kinase localization. Mosaic analysis in both the soma and germline demonstrates that Doa function is essential for cell viability. Finally, in contrast to results reported in other systems and despite some phenotypic similarities, genetic data demonstrate that the LAMMER kinases do not participate in the ras-MAP kinase signal transduction pathway. Waksman Institute, Rutgers University, Piscataway, New Jersey 08855, USA. Yun B B Lee K K Farkas R R Hitte C C Rabinow L L eng Journal Article

UNITED STATES Genetics 0374636 0 Isoenzymes EC 2.7.1.- Doa kinase EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Cell Nucleus enzymology Crosses, Genetic Cytoplasm enzymology Drosophila melanogaster embryology enzymology genetics growth & development Embryo, Nonmammalian enzymology physiology Female Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Germ-Line Mutation Isoenzymes genetics metabolism Larva Male Mosaicism Protein-Serine-Threonine Kinases genetics metabolism Sex Determination (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription, Genetic FBrf0100033 98104259 9441692 1998 02 13 1998 02 13 2000 12 18

0012-1606 192 2 1997 Dec 15 Novel segment polarity gene interactions during embryonic head development in Drosophila. 599-613 In the trunk of the Drosophila embryo, the segment polarity genes are initially activated by the pair-rule genes, and later maintain each other's expression through a complex network of cross-regulatory interactions. These interactions, which are critical to cell fate specification, are similar in each of the trunk segments. To determine whether segment polarity gene expression is established differently outside the trunk, we studied the regulation of the genes hedgehog (hh), wingless (wg), and engrailed (en) in each of the segments of the developing head. We show that the cross-regulatory relationships among these genes, as well as their initial mode of activation, in the anterior head are significantly different from those in the trunk. In addition, each head segment exhibits a unique network of segment polarity gene interactions. We propose that these segment-specific interactions evolved to specify the high degree of structural diversity required for head morphogenesis. Department of Neuroscience, University of Pennsylvania, Philadelphia 19104-6074, USA. Gallitano-Mendel A A Finkelstein R R eng F30 MH10161 MH NIMH R01 GM47985 GM NIGMS Journal Article

UNITED STATES Dev Biol 0372762 0 Homeodomain Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 engrail protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Drosophila melanogaster embryology genetics Embryo, Nonmammalian ultrastructure Eye embryology Gene Expression Regulation, Developmental Genes, Regulator Head embryology Homeodomain Proteins genetics physiology Insect Proteins genetics physiology Morphogenesis genetics Proto-Oncogene Proteins genetics physiology Sense Organs embryology Support, U.S. Gov't, P.H.S. Transcription Factors genetics physiology FBrf0129810 20469359 11014820 2000 10 25 2000 11 30 2001 11 02

0016-6731 156 2 2000 Oct Identification of genomic regions that interact with a viable allele of the Drosophila protein tyrosine phosphatase corkscrew. 733-48 Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of developmental decisions and processes. Among the molecules known to transduce the RTK-generated signal is the nonreceptor protein tyrosine phosphatase Corkscrew (Csw). Previously, Csw has been demonstrated to function throughout the Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso, Sevenless, EGF, and Breathless/FGF RTK pathways. While the biochemical function of Csw remains to be unambiguously elucidated, current evidence suggests that Csw plays more than one role during transduction of the RTK signal and, further, the molecular mechanism of Csw function differs depending upon the RTK in question. The isolation and characterization of a new, spontaneously arising, viable allele of csw, csw(lf), has allowed us to undertake a genetic approach to identify loci required for Csw function. The rough eye and wing vein gap phenotypes exhibited by adult flies homo- or hemizygous for csw(lf) has provided a sensitized background from which we have screened a collection of second and third chromosome deficiencies to identify 33 intervals that enhance and 21 intervals that suppress these phenotypes. We have identified intervals encoding known positive mediators of RTK signaling, e.g., drk, dos, Egfr, E(Egfr)B56, pnt, Ras1, rolled/MAPK, sina, spen, Src64B, Star, Su(Raf)3C, and vein, as well as known negative mediators of RTK signaling, e.g., aos, ed, net, Src42A, sty, and su(ve). Of particular interest are the 5 lethal enhancing intervals and 14 suppressing intervals for which no candidate genes have been identified. Department of Biological Sciences, University of Manchester, Manchester M13 9PT, England. Firth L L Manchester J J Lorenzen J A JA Baron M M Perkins L A LA eng F32GM17901 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 3.1.3.- corkscrew protein EC 3.1.3.48 Protein-Tyrosine-Phosphatase IM Alleles Animal Animals, Genetically Modified Chromosome Mapping Crosses, Genetic Drosophila melanogaster enzymology genetics growth & development Eye growth & development ultrastructure Female Germ-Line Mutation Heterozygote Homozygote Larva Male Mosaicism Phenotype Protein-Tyrosine-Phosphatase genetics metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0158867 22575354 12690448 2003 04 11

0949-944X 213 3 2003 Apr Mutations in lozenge and D-Pax2 invoke ectopic patterned cell death in the developing Drosophila eye using distinct mechanisms. 107-19 Mutations in the lozenge gene of Drosophila melanogaster elicit a pleiotropic set of adult phenotypes, including severe compound eye perturbations resulting from the defective recruitment of photoreceptors R1/6 and R7, cone and pigment cells. In this study, we show that excessive patterned apoptosis is evident at the same developmental stage in these lozenge mutants. In lozenge null mutants, apoptosis occurs prior to lozenge-dependent cell fate specification. A second gene, D-Pax2, genetically interacts with lozenge. Interestingly, D-Pax2 mutants also exhibit increased cell death, but slightly later in development than that in lozenge mutants. Although expression of the caspase inhibitor p35 eliminates death in both lozenge and D-Pax2 mutants, the lozenge mutant eye phenotypes persist because other normal Lozenge functions are still lacking. D-Pax2 eye phenotypes, in contrast, are dramatically altered in a p35 background, because cells that normally differentiate as cone and primary pigment cells are subsequently transformed into secondary pigment cells. This study leads us to propose that Lozenge, aside from its known role in gene regulation of cell-specific transcription factors, is required to contribute to the repression of cell death mechanisms, creating a permissive environment for the survival of undifferentiated cells in early eye development. Lack of lozenge expression increases the likelihood that an undifferentiated cell will initiate its default death program and die prematurely. The ectopic cell death evident in D-Pax2 mutants appears to arise from the cell fate transformation of cone cells into secondary pigment cells, either autonomously or as a result of defective signalling. Department of Genetics, University of Melbourne, Parkville, Victoria, Australia. Siddall Nicole A NA Behan Kristina Jackson KJ Crew Jennifer R JR Cheung Tara L TL Fair Jason A JA Batterham Philip P Pollock John Archie JA eng Journal Article 2003 02 22

Germany Dev Genes Evol 9613264 IM FBrf0086700 96366429 8770606 1996 10 23 1996 10 23 2002 11 01

0016-6731 142 1 1996 Jan Evolution of Antennapedia-class homeobox genes. 295-303 Antennapedia (Antp)-class homeobox genes are involved in the determination of pattern formation along the anterior-posterior axis of the animal embryo. A phylogenetic analysis of Antp-class homeodomains of the nematode, Drosophila, amphioxus, mouse, and human indicates that the 13 cognate group genes of this gene family can be divided into two major groups, i.e., groups I and II. Group I genes can further be divided into subgroups A (cognate groups 1-2), B (cognate group 3), and C (cognate groups 4-8), and group II genes can be divided into subgroups D (cognate groups 9-10) and E (cognate groups 11-13), though this classification is somewhat ambiguous. Evolutionary distances among different amino acid sequences suggest that the divergence between group I and group II genes occurred approximately 1000 million years (MY) ago, and the five different subgroups were formed by approximately 600 MY ago, probably before the divergence of Pseudocoelomates (e.g., nematodes) and Coelomates (e.g., insects and chordates). Our results show that the genes that are phylogenetically close are also closely located in the chromosome, suggesting that the colinearity between the gene expression and gene arrangement was generated by successive tandem gene duplications and that the gene arrangement has been maintained by some sort of selection. Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park 16802, USA. Zhang J J Nei M M eng Journal Article

UNITED STATES Genetics 0374636 0 Antennapedia homeodomain protein 0 Homeodomain Proteins IM Animal Caenorhabditis elegans embryology genetics Chordata, Nonvertebrate embryology genetics Drosophila melanogaster embryology genetics Embryo and Fetal Development genetics Evolution Genes, Helminth Genes, Homeobox Genes, Insect Homeodomain Proteins genetics Human Mice Multigene Family Phylogeny Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0085498 96119059 8533161 1996 02 01 1996 02 01 2000 12 18

0168-9525 11 12 1995 Dec The genetic basis of quantitative variation: numbers of sensory bristles of Drosophila melanogaster as a model system. 464-70 The numbers of sensory hairs of Drosophila melanogaster present an ideal model system to elucidate the genetic basis of morphological quantitative variation. Loci affecting bristle number can be identified and their properties studied by accumulating spontaneous mutations, by P element mutagenesis, by mapping factors causing divergence between selection lines and by the association of phenotype variation with molecular variation at candidate neurogenic loci. The consensus emerging from the application of all approaches is that much of the mutational and segregating variation affecting bristle number is attributable to alleles with large phenotype effects at a small number of candidate loci. Department of Genetics, North Carolina State University, Raleigh, NC 27695-7614, USA. Mackay T F TF eng Journal Article Review Review, Tutorial

ENGLAND Trends Genet 8507085 IM Animal Crosses, Genetic Drosophila melanogaster anatomy & histology genetics Female Genes, Insect Male Models, Genetic Mutagenesis, Insertional Mutation Support, U.S. Gov't, P.H.S. Variation (Genetics) 35 FBrf0080345 95180488 7875369 1995 04 03 1995 04 03 2000 12 18

0012-1606 167 2 1995 Feb Cellular events during development of the olfactory sense organs in Drosophila melanogaster. 426-38 The olfactory sensilla on the antenna of adult Drosophila melanogaster develop during the first 36 hr after pupariation, from their anlagen in the cephalic disc. We have used tissue-specific beta-galactosidase expression in the enhancer trap strain A101.IF3 and the monoclonal antibody 22C10 as sensory cell markers, as well as the lineage tracer 5-bromo-2'-deoxyuridine (BrdU), to describe this process. The development of an olfactory sensillum begins with the selection of a "founder cell" (FC). These cells are distinct in that they possess large apically located nuclei revealed by beta-galactosidase expression in A101.IF3. In the following 6 hr, a few cells neighboring the FC also start expressing beta-galactosidase and together comprise a group. Cells of this group, denoted a "presensillum-cluster" (PSC), undergo at least one round of replication and give rise to all of the cells of a sensillum. A subset of the cells within each PSC and, later, all the sensory neurons are recognized by MAb22C10. The antennae of the mutant lozenge3 (lz3) lack all basiconic and some trichoid sensilla. The mutation apparently affects early steps in sensillum development and many of the FCs fail to form. Those that are present, however, proceed to form mature olfactory sensilla. Therefore, we conclude that the selection of an FC is the first step in olfactory sense organ development. Our study reveals novel aspects of sensory development in Drosophila. Molecular Biology Unit, Tata Institute of Fundamental Research, Colaba, Bombay, India. Ray K K Rodrigues V V eng Journal Article

UNITED STATES Dev Biol 0372762 0 Biological Markers EC 3.2.1.23 beta-Galactosidase IM Animal Biological Markers Cell Differentiation Cell Division Drosophila melanogaster enzymology genetics growth & development Genes, Insect Immunohistochemistry Neurons, Afferent cytology Sense Organs enzymology growth & development Smell genetics physiology Stem Cells cytology Support, Non-U.S. Gov't beta-Galactosidase genetics metabolism FBrf0145162 21848411 11859370 2002 02 22 2002 04 19

0028-0836 415 6874 2002 Feb 21 Hox protein mutation and macroevolution of the insect body plan. 914-7 A fascinating question in biology is how molecular changes in developmental pathways lead to macroevolutionary changes in morphology. Mutations in homeotic (Hox) genes have long been suggested as potential causes of morphological evolution, and there is abundant evidence that some changes in Hox expression patterns correlate with transitions in animal axial pattern. A major morphological transition in metazoans occurred about 400 million years ago, when six-legged insects diverged from crustacean-like arthropod ancestors with multiple limbs. In Drosophila melanogaster and other insects, the Ultrabithorax (Ubx) and abdominal A (AbdA, also abd-A) Hox proteins are expressed largely in the abdominal segments, where they can suppress thoracic leg development during embryogenesis. In a branchiopod crustacean, Ubx/AbdA proteins are expressed in both thorax and abdomen, including the limb primordia, but do not repress limbs. Previous studies led us to propose that gain and loss of transcriptional activation and repression functions in Hox proteins was a plausible mechanism to diversify morphology during animal evolution. Here we show that naturally selected alteration of the Ubx protein is linked to the evolutionary transition to hexapod limb pattern. Section of Cell and Developmental Biology, Universith of California--San Diego, Jolla, CA 92093, USA. Ronshaugen Matthew M McGinnis Nadine N McGinnis William W eng Journal Article

England Nature 0410462 0 Chimeric Proteins 0 DNA-Binding Proteins 0 Drosophila Proteins 0 ultrabithorax protein IM Nature. 2002 Feb 21;415(6874):848-9 11859349 Amino Acid Sequence Animal Animals, Genetically Modified Artemia anatomy & histology genetics Body Patterning Chimeric Proteins biosynthesis genetics Crosses, Genetic DNA-Binding Proteins genetics physiology Drosophila Proteins genetics physiology Drosophila melanogaster anatomy & histology genetics Evolution Evolution, Molecular Extremities Female Genes, Homeobox Male Molecular Sequence Data Protein Structure, Tertiary Selection (Genetics) Support, U.S. Gov't, P.H.S. FBrf0104428 98378585 9712586 1998 09 08 1998 09 08 2000 12 18

0036-8075 281 5380 1998 Aug 21 Determinants of kinesin motor polarity. 1200-2 The kinesin motor protein family members move along microtubules with characteristic polarity. Chimeric motors containing the stalk and neck of the minus-end-directed motor, Ncd, fused to the motor domain of plus-end-directed kinesin were analyzed. The Ncd stalk and neck reversed kinesin motor polarity, but mutation of the Ncd neck reverted the chimeric motor to plus-end movement. Thus, residues or regions contributing to motor polarity must be present in both the Ncd neck and the kinesin motor core. The neck-motor junction was critical for Ncd minus-end movement; attachment of the neck to the stalk may also play a role. Department of Microbiology, Duke University Medical Center, Durham, NC 27710, USA. endow@galactose.mc.duke.edu Endow S A SA Waligora K W KW eng Journal Article

UNITED STATES Science 0404511 0 Chimeric Proteins 0 ncd protein EC 3.6.1.- Kinesin IM Amino Acid Sequence Animal Chimeric Proteins chemistry metabolism Drosophila melanogaster Kinesin chemistry genetics metabolism Microtubules metabolism Molecular Sequence Data Mutation Protein Structure, Secondary Support, U.S. Gov't, P.H.S. FBrf0098758 97470979 9326622 1997 11 24 1997 11 24 2000 12 18

0027-8424 94 21 1997 Oct 14 Proximo-distal specification in the wing disc of Drosophila by the nubbin gene. 11405-10 Mutations in the nubbin (nub) gene have a phenotype consisting of a severe wing size reduction and pattern alterations, such as transformations of distal elements into proximal ones. nub expression is restricted to the wing pouch cells in wing discs since early larval development. These effects are also observed in genetic mosaics where cell proliferation is reduced in all wing blade regions autonomously, and transformation into proximal elements is observed in distal clones. Clones located in the proximal region of the wing blade cause in addition nonautonomous reduction of the whole wing. Cell lineage experiments in a nub mutant background show that clones respect neither the anterior-posterior nor the dorsal-ventral boundary but that the selector genes have been correctly expressed since early larval development. The phenotypes of nub el and nub dpp genetic combinations are synergistic and the overexpression of dpp in clones in nub wings does not result in overproliferation of the surrounding wild-type cells. We discuss the role of nub in the wing's proximo-distal axis and in the formation of compartment boundaries. Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Cantoblanco 28049 Madrid, Spain. Cifuentes F J FJ García-Bellido A A eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Homeodomain Proteins 0 Insect Proteins 0 pdm protein IM Animal Drosophila melanogaster physiology radiation effects Gene Expression Regulation, Developmental Genes, Insect Homeodomain Proteins biosynthesis genetics Insect Proteins biosynthesis Larva Mitosis Morphogenesis Mutagenesis Recombination, Genetic radiation effects Support, Non-U.S. Gov't Wing X-Rays FBrf0051860 90337316 2116360 1990 09 10 1990 09 10 2000 12 18

0890-9369 4 5 1990 May Alternative splicing of the sex determination gene transformer-2 is sex-specific in the germ line but not in the soma. 789-805 The transformer-2 (tra-2) gene of Drosophila melanogaster plays essential roles in both sexual differentiation in the female soma and spermatogenesis in the male germ line. In the female soma, tra-2 is known to act with other genes in the sex determination regulatory cascade to control the sex-specific alternative splicing of transcripts from the doublesex gene. Here, we determine whether or not any sex-specific tra-2 products are expressed that may account for either of these sex-specific activities. Sequence analysis of the tra-2 gene and 10 tra-2 cDNA clones coupled with nuclease protection analysis reveals a variety of alternatively spliced tra-2 mRNAs that each encode one of four distinct but overlapping polypeptides. Three of the encoded polypeptides contain both a ribonucleoprotein consensus sequence and arginine/serine-rich regions, suggesting a direct role for these products in RNA splicing. We show that although two transcripts are expressed male specifically in the germ line, the tra-2 transcripts expressed in the soma are not sex-specific. The translation of products from a tra-2-lacZ fusion gene in both sexes suggests that the female-specific functioning of tra-2 in somatic tissues is not attributable to a translational mechanism. We suggest that tra-2 activity in somatic tissues is regulated through a post-translational sex-specific interaction with the product of the tra gene rather than through the expression of a female-specific tra-2 polypeptide. Department of Biological Sciences, Stanford University, California 94305. Mattox W W Palmer M J MJ Baker B S BS eng GENBANK M30939 M30940 M76381 P41RRR01685 RR NCRR Journal Article

UNITED STATES Genes Dev 8711660 0 RNA, Messenger 0 Recombinant Fusion Proteins IM Amino Acid Sequence Animal Base Sequence Drosophila melanogaster genetics Female Gene Expression Regulation Genes Germ Cells metabolism Male Molecular Sequence Data RNA Splicing RNA, Messenger metabolism Recombinant Fusion Proteins biosynthesis genetics Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Translation, Genetic FBrf0111327 99425438 10494038 1999 10 08 1999 10 08 2000 12 18

1021-7770 6 5 1999 Sep-Oct Signal transduction pathway for anterior-posterior development in Drosophila. 314-9 In Drosophila, the establishment of embryonic polarity along the anterior-posterior axis of the egg is determined by the activity of maternal gene products that accumulate during oogenesis. Amongst these are the Bicoid, the Nanos, and the terminal class gene products, some of which are oncoproteins involved in signal transduction for the formation of terminal structures in the embryo. Several signal transduction pathways have been described in Drosophila, and this review explores the potential of oncogene studies using one of those pathways - the terminal class signal transduction pathway - to better understand the cellular mechanisms of proto-oncogenes that mediate cellular responses in vertebrates including humans. Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass. 02115, USA. baek@rascal.med.harvard.edu Baek K H KH Lee K Y KY eng Journal Article Review Review, Tutorial

SWITZERLAND J Biomed Sci 9421567 EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Animal Body Patterning genetics Drosophila melanogaster embryology enzymology genetics Genes, Insect genetics physiology Human Phosphorylation Proto-Oncogene Proteins c-raf genetics metabolism Signal Transduction Support, Non-U.S. Gov't 55 FBrf0053362 92005710 1913825 1991 11 21 1991 11 21 2001 11 02

0092-8674 67 2 1991 Oct 18 A role for the Drosophila neurogenic genes in mesoderm differentiation. 311-23 The neurogenic genes of Drosophila have long been known to regulate cell fate decisions in the developing ectoderm. In this paper we show that these genes also control mesoderm development. Embryonic cells that express the muscle-specific gene nautilus are overproduced in each of seven neurogenic mutants (Notch, Delta, Enhancer of split, big brain, mastermind, neuralized, and almondex), at the apparent expense of neighboring, nonexpressing mesodermal cells. The mesodermal defect does not appear to be a simple consequence of associated neural hypertrophy, suggesting that the neurogenic genes may function similarly and independently in establishing cell fates in both ectoderm and mesoderm. Altered patterns of beta 3-tubulin and myosin heavy chain gene expression in the mutants indicate a role for the neurogenic genes in development of most visceral and somatic muscles. We propose that the signal produced by the neurogenic genes is a general one, effective in both ectoderm and mesoderm. Laboratory of Genetics, Rockefeller University, New York, New York. Corbin V V Michelson A M AM Abmayr S M SM Neel V V Alcamo E E Maniatis T T Young M W MW eng 5P01GM29301 GM NIGMS GM5-25103 GM NIGMS Journal Article

UNITED STATES Cell 0413066 0 DNA Probes 0 Tubulin EC 1.11.1.- Horseradish Peroxidase EC 3.6.1.4 Myosins IM E(spl) amx bib mam neu Animal Cell Differentiation physiology DNA Probes metabolism Drosophila melanogaster embryology genetics Gene Expression physiology Genes, Regulator physiology Horseradish Peroxidase Mesoderm cytology metabolism Muscles cytology metabolism Mutation genetics Myosins biosynthesis Neurons cytology physiology Nucleic Acid Hybridization Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic physiology Tubulin biosynthesis FBrf0043047 86088365 3935767 1986 02 18 1986 02 18 2000 12 18

0167-7063 2 5 1985 Nov Genetic interactions in early neurogenesis of Drosophila melanogaster. 291-308 A number of genetic loci, called neurogenic, have been found to be involved in directing the segregation of neural and epidermal lineages within the ectodermal germ layer of Drosophila melanogaster. With the aim of understanding the regulation of this developmental function we have studied interactions of the loci N, Dl and E(spl) among each other and with another locus (H), by means of increasing and decreasing the number of wild-type copies of one of these genes in the presence of mutations in another one. The results reveal functional community which exists among these neurogenic loci. E(spl) overlaps functionally with both N and Dl because genotypes involving only one copy of E(spl)+ and either an N or Dl mutation are lethal. Furthermore the normal H+ allele behaves as if it represses the activity of the 3 neurogenic loci; and, whereas E(spl) seems to be a close target of H repressing action, the influence of H upon the other two seems to be indirect. Vässin H H Vielmetter J J Campos-Ortega J A JA eng Journal Article

NETHERLANDS J Neurogenet 8406473 IM Alleles Animal Cell Differentiation Drosophila melanogaster embryology genetics growth & development Ectoderm innervation physiology Epidermis physiology Gene Expression Regulation Genes, Lethal Genotype Heterozygote Homozygote Mutation Nervous System embryology growth & development Phenotype Support, Non-U.S. Gov't FBrf0049398 89208364 2495849 1989 05 26 1989 05 26 2000 12 18

0922-3371 26 2 1989 Mar Maternal and embryonic transcripts of Drosophila proto-oncogenes are expressed in Schneider 2 culture cells but not in l(2)gl transformed neuroblasts. 79-86 The transcription patterns of Drosophila melanogaster src, abl and two ras homologs were analyzed in normal Drosophila tissue, in neuroblasts derived from tumorous larval brain of the mutant lethal(2)giant larvae [l(2)gl] and in Schneider 2 tissue culture cells. Our results show that, in addition to constitutive transcripts, the src, abl, ras1 and ras3 genes express a set of maternal/embryonic-specific transcripts. By using these transcripts as differentiation markers we show that, in spite of their embryonic-like, undifferentiated phenotype, the l(2)gl transformed neuroblasts are authentic larval cells. Using the same criterion the Schneider 2 tissue culture cells show the characteristics of embryonic cells. Department of Biology, Technion-Israel Institute of Technology, Haifa. Kimchie Z Z Segev O O Lev Z Z eng Journal Article

IRELAND Cell Differ Dev 8811335 9007-49-2 DNA IM Animal Cell Line DNA diagnostic use Drosophila melanogaster cytology genetics Embryo, Nonmammalian Female Gene Expression Regulation Neurons metabolism Nucleic Acid Hybridization Proto-Oncogenes Support, Non-U.S. Gov't Tumor Cells, Cultured metabolism FBrf0059035 93180785 8441386 1993 04 01 1993 04 01 2000 12 18

0270-7306 13 3 1993 Mar Regulated splicing of the Drosophila sex-lethal male exon involves a blockage mechanism. 1408-14 In Drosophila melanogaster, sex determination in somatic cells is controlled by a cascade of genes whose expression is regulated by alternative splicing [B. S. Baker, Nature (London) 340:521-524, 1989; J. Hodgkin, Cell 56:905-906, 1989]. The master switch gene in this hierarchy is Sex-lethal. Sex-lethal is turned on only in females, and an autoregulatory feedback loop which controls alternative splicing maintains this state (L. R. Bell, J. I. Horabin, P. Schedl, and T. W. Cline, Cell 65:229-239, 1991; L. N. Keyes, T. W. Cline, and P. Schedl, Cell 68:933-943, 1992). Sex-lethal also promotes female differentiation by controlling the splicing of RNA from the next gene in the hierarchy, transformer. Sosnowski et al. (B. A. Sosnowski, J. M. Belote, and M. McKeown, Cell 58:449-459, 1989) have shown that the mechanism for generating female transformer transcripts is not through the activation of the alternative splice site but by the blockage of the default splice site. We have tested whether an activation or a blockage mechanism is involved in Sex-lethal autoregulation. The male exon of Sex-lethal with flanking splice sites was placed into the introns of heterologous genes. Our results support the blockage mechanism. The poly(U) run at the male exon 3' splice site is required for sex-specific splicing. However, unlike transformer, default splicing to the male exon is sensitive to the sequence context within which the exon resides. This and the observation that the splice signals at the exon are suboptimal are discussed with regard to alternate splicing. Department of Molecular Biology, Princeton University, New Jersey 08544. Horabin J I JI Schedl P P eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 RNA Precursors 27416-86-0 Poly U IM Sxl tra Alternative Splicing Animal Base Sequence Comparative Study Drosophila melanogaster genetics Exons genetics Female Genes, Insect genetics Genes, Lethal genetics Male Molecular Sequence Data Poly U genetics RNA Precursors metabolism Sequence Analysis Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0086425 96194038 8631257 1996 07 02 1996 07 02 2003 06 16

0950-1991 122 3 1996 Mar Polyembryonic development: insect pattern formation in a cellularized environment. 795-804 THe polyembryonic wasp Copidosoma floridanum produces up to 2000 individuals from a single egg. During the production of individual embryos the original anteroposterior axis of the egg is lost and axial patterning must subsequently be reestablished within each embryo. The mechanism by which this occurs is unknown. In most insects, egg polarity is established during oogenesis and early development takes place in a syncytium. In Drosophila melanogaster, the syncytium is considered essential for establishing the morphogenetic gradients that initiate segmental patterning. However, we found that development of C. floridanum occurs almost exclusively in a cellularized environment. To determine whether the D. melanogaster patterning cascade is conserved in the absence of a syncytium, we analyzed the expression of Even-skipped, Engrailed and Ultrabithorax/Abdominal-A during polyembryonic development. Here we show that in spite of the absence of a syncytium, the elements of the D. melanogaster segmentation hierarchy are conserved. The segment-polarity gene Engrailed and the homeotic genes Ultrabithorax/Abdominal-A are expressed in a conserved pattern relative to D. melanogaster. However, we detect an alteration in the expression of the Even-skipped antigen. Even-skipped is initially expressed in segmentally reiterated stripes and not in the pair-rule pattern as it is in D. melanogaster. We also observe that the expression of these regulatory proteins does not occur during the early proliferative phases of polyembryony. Our results indicate that a syncytium is not required for segmental patterning in this insect. Developmental Biology Program and Department of Entomology, University of Wisconsin, Madison 53076, USA. Grbic M M Nagy L M LM Carroll S B SB Strand M M eng Journal Article

ENGLAND Development 8701744 0 Antibodies, Monoclonal 0 DNA-Binding Proteins 0 ESPD protein, E coli 0 Homeodomain Proteins 0 engrailed 1 protein 108911-13-3 even-skipped protein, Drosophila IM Animal Antibodies, Monoclonal DNA-Binding Proteins metabolism Gene Expression Regulation, Developmental Genes, Homeobox Homeodomain Proteins metabolism Morphogenesis Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Wasps embryology FBrf0100576 98129845 9461626 1998 03 23 1998 03 23 2000 12 18

0021-9258 273 7 1998 Feb 13 In vivo analysis of Argos structure-function. Sequence requirements for inhibition of the Drosophila epidermal growth factor receptor. 4275-81 The Drosophila Argos protein is the only known extracellular inhibitor of the epidermal growth factor receptor (EGFR). It is structurally related to the activating ligands, in that it is a secreted protein with a single epidermal growth factor (EGF) domain. To understand the mechanism of Argos inhibition, we have investigated which regions of the protein are essential. A series of deletions were made and tested in vivo; furthermore, by analyzing chimeric proteins between Argos and the activating ligand, Spitz (a transforming growth factor-alpha-like factor), we have examined what makes one inhibitory and the other activating. Our results reveal that Argos has structural requirements that differ from all known EGFR activating ligands; domains flanking the EGF domain are essential for its function. We have also defined the important regions of the atypical Argos EGF domain. The extended B-loop is necessary, whereas the C-loop can be replaced with the equivalent Spitz region without substantially affecting Argos function. Comparison of the argos genes from Drosophila melanogaster and the housefly, Musca domestica, supports our structure-function analysis. These studies are a prerequisite for understanding how Argos inhibits the Drosophila EGFR and provide a basis for designing mammalian EGFR inhibitors. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. Howes R R Wasserman J D JD Freeman M M eng Journal Article

UNITED STATES J Biol Chem 2985121R 0 Eye Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Recombinant Fusion Proteins 147954-53-8 gil protein 148175-53-5 spitz protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Amino Acid Sequence Animal Conserved Sequence genetics Drosophila melanogaster chemistry embryology Eye growth & development ultrastructure Eye Proteins chemistry genetics pharmacology Gene Expression Regulation, Developmental genetics Houseflies chemistry Membrane Proteins chemistry genetics pharmacology Microscopy, Electron, Scanning Molecular Sequence Data Nerve Tissue Proteins chemistry genetics pharmacology Receptor, Epidermal Growth Factor antagonists & inhibitors metabolism Recombinant Fusion Proteins genetics Sequence Alignment Sequence Deletion genetics Structure-Activity Relationship Support, Non-U.S. Gov't Wing growth & development FBrf0137058 21283224 11389437 2001 06 04 2001 09 20 2003 06 16

1465-7392 3 6 2001 Jun Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. 538-43 The mammalian cis-trans prolyl isomerase Pin1 and its yeast orthologue Ess1/Ptf1 have been implicated in cell cycle control but a correlation between biochemical and physiological functions has not been established conclusively. Pin1 targets the proline residue carboxy-terminal to the phosphorylated threonine or serine residue, which constitutes part of the phosphorylated mitogen-activated protein kinase (MAPK) site PXpT/SP. Here we show that the Drosophila Pin1 homologue, the Dodo protein, is involved in dorsoventral patterning of the follicular epithelium in the egg chamber. Its function is to facilitate the degradation of transcription factor CF2, which requires, a priori, activated epidermal growth factor receptor-MAPK signalling. Laboratory of Cancer Genomics, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, South Carolina 29425, USA. hsut@musc.edu Hsu T T McRackan D D Vincent T S TS Gert de Couet H H eng Journal Article

England Nat Cell Biol 100890575 0 DNA-Binding Proteins 0 Insect Proteins 0 Transcription Factors 0 Ubiquitins 148813-47-2 transcription factor CF2 EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 5.2.1.- Pin1 protein EC 5.2.1.8 Dodo protein, Drosophila EC 5.2.1.8 Peptidylprolyl Isomerase IM Nat Cell Biol. 2001 Jun;3(6):E136-7 11389451 Animal DNA-Binding Proteins metabolism Drosophila melanogaster enzymology metabolism Insect Proteins metabolism Mitogen-Activated Protein Kinases metabolism Oogenesis physiology Peptidylprolyl Isomerase chemistry metabolism Phosphorylation Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Ubiquitins metabolism FBrf0127231 20183617 10716936 2000 04 27 2000 04 27 2003 06 16

0261-4189 19 6 2000 Mar 15 Distinct roles of two conserved Staufen domains in oskar mRNA localization and translation. 1366-77 Drosophila Staufen protein is required for the localization of oskar mRNA to the posterior of the oocyte, the anterior anchoring of bicoid mRNA and the basal localization of prospero mRNA in dividing neuroblasts. The only regions of Staufen that have been conserved throughout animal evolution are five double-stranded (ds)RNA-binding domains (dsRBDs) and a short region within an insertion that splits dsRBD2 into two halves. dsRBDs 1, 3 and 4 bind dsRNA in vitro, but dsRBDs 2 and 5 do not, although dsRBD2 does bind dsRNA when the insertion is removed. Full-length Staufen protein lacking this insertion is able to associate with oskar mRNA and activate its translation, but fails to localize the RNA to the posterior. In contrast, Staufen lacking dsRBD5 localizes oskar mRNA normally, but does not activate its translation. Thus, dsRBD2 is required for the microtubule-dependent localization of osk mRNA, and dsRBD5 for the derepression of oskar mRNA translation, once localized. Since dsRBD5 has been shown to direct the actin-dependent localization of prospero mRNA, distinct domains of Staufen mediate microtubule- and actin-based mRNA transport. Wellcome/CRC Institute, Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. Micklem D R DR Adams J J Grünert S S St Johnston D D eng Journal Article

ENGLAND EMBO J 8208664 0 Actins 0 Homeodomain Proteins 0 Insect Proteins 0 RNA, Double-Stranded 0 RNA, Messenger 0 RNA-Binding Proteins 0 Trans-Activators 0 bicoid protein, Drosophila 0 oskar protein, Drosophila 139568-71-1 staufen protein, Drosophila IM S Actins metabolism Amino Acid Sequence Animal Biological Transport Body Patterning genetics Conserved Sequence genetics Drosophila melanogaster cytology embryology genetics Evolution, Molecular Gene Expression Regulation, Developmental Genetic Complementation Test Homeodomain Proteins genetics Insect Proteins genetics metabolism Microtubules metabolism Models, Molecular Molecular Sequence Data Oocytes growth & development metabolism Protein Structure, Tertiary RNA, Double-Stranded genetics metabolism RNA, Messenger genetics metabolism RNA-Binding Proteins chemistry genetics metabolism Sequence Alignment Sequence Deletion genetics Support, Non-U.S. Gov't Trans-Activators genetics Transgenes genetics physiology Translation, Genetic genetics FBrf0091407 97164376 9011067 1997 03 14 1997 03 14 2002 10 21

0340-7594 180 2 1997 Feb The maxillary palp of Drosophila: ultrastructure and physiology depends on the lozenge gene. 143-50 The ultrastructure and physiology of the maxillary palp of Drosophila melanogaster have been studied in wild-type and lozenge mutants. Olfactory physiology in the maxillary palp is shown to depend upon the lozenge(lz) gene. Reduced response amplitudes were recorded for all odorants tested, and the physiological defect was shown to map to the lz locus. The structure of the maxillary palp sensilla is described by scanning electron microscopy (SEM) at high magnification, initially in the wild-type. A linear arrangement of pores, connected by furrows, was found in one class of sensilla, the basiconic sensilla. In the lz3 mutant, morphological alterations in the basiconic sensilla and duplications of sensilla are documented by SEM. The correlation of structural abnormalities in the lz sensilla and physiological abnormalities in odorant response are consistent with an olfactory role for the basiconic sensilla of the maxillary palp. Department of Biology, Yale University, New Haven, CT 06520-8103, USA. Riesgo-Escovar J R JR Piekos W B WB Carlson J R JR eng RO1 DC02174-10 DC NIDCD Journal Article

GERMANY J Comp Physiol [A] 8413199 0 Transcription Factors 0 lozenge protein, Drosophila IM Animal Drosophila Microscopy, Electron Olfactory Bulb physiology ultrastructure Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors physiology ultrastructure FBrf0092630 97190181 9038336 1997 03 17 1997 03 17 2003 06 16

0092-8674 88 4 1997 Feb 21 roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. 445-57 The Drosophila roX1 gene is X-linked and produces RNAs that are male-specific, somatic, and preferentially expressed in the central nervous system. These RNAs are retained in the nucleus and lack any significant open reading frame. Although all sexually dimorphic characteristics in Drosophila were thought to be controlled by the sex determination pathway through the gene transformer (tra), the expression of roX1 is independent of tra activity. Instead, the dosage compensation system is necessary and sufficient for the expression of roX1. Consistent with a potential function in dosage compensation, roX1 RNAs localize specifically to the male X chromosome. This localization occurs even when roX1 RNAs are expressed from autosomal locations in X-to-autosome translocations. The novel regulation and subnuclear localization of roX1 RNAs makes them candidates for an RNA component of the dosage compensation machinery. Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA. Meller V H VH Wu K H KH Roman G G Kuroda M I MI Davis R L RL eng GENBANK U97114 Journal Article

UNITED STATES Cell 0413066 0 Insect Hormones 0 Nuclear Proteins 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 0 Transcription Factors 0 male-specific lethal-2 protein 0 transformer protein, Drosophila 144515-64-0 maleless protein, Drosophila 63231-63-0 RNA IM Animal Base Sequence Blastoderm physiology Drosophila melanogaster genetics Female Gene Dosage Gene Expression Regulation, Developmental physiology In Situ Hybridization Insect Hormones genetics Linkage (Genetics) Male Molecular Sequence Data Mutation physiology Nuclear Proteins genetics Open Reading Frames genetics RNA analysis RNA-Binding Proteins genetics Sex Characteristics Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics Transcription, Genetic physiology X Chromosome Y Chromosome FBrf0052644 90206053 1690860 1990 05 03 1990 05 03 2000 12 18

0028-0836 344 6265 1990 Mar 29 Binding of the Drosophila sex-lethal gene product to the alternative splice site of transformer primary transcript. 461-3 Somatic sexual differentiation in Drosophila melanogaster is accomplished by a hierarchy of genes of which one, Sex-lethal (Sxl), is required for the functional female-specific splicing of the transcripts of the immediately downstream regulatory gene, transformer (tra). The first exon of the tra primary transcript is spliced to one of two acceptor sites. Splicing to the upstream site yields a messenger RNA which is neither sex-specific nor functional, but that produced after splicing to the downstream acceptor site yields a functional female-specific mRNA. Here we address the question of how the Sxl gene product determines the alternative splicing of tra primary transcripts. One suggestion is that non-sex-specific splicing to the upstream acceptor is blocked in female flies by sex-specific factors, but neither the identity of the female-specific factors nor the mechanism of the blockage has been specified. We have now performed co-transfection experiments in which Sxl complementary DNA and the tra gene are expressed in Drosophila Kc cells. Moreover, we find that female Sxl-encoded protein binds specifically to the tra transcript at or near the non-sex-specific acceptor site, implying that the female Sxl gene product is the trans-acting factor that regulates the alternative splicing. Department of Biophysics, Faculty of Science, Kyoto University, Japan. Inoue K K Hoshijima K K Sakamoto H H Shimura Y Y eng Journal Article

ENGLAND Nature 0410462 0 Plasmids 0 RNA Precursors 0 RNA, Messenger 0 Trans-Activators 63231-63-0 RNA 9007-49-2 DNA IM Animal Base Sequence Binding Sites DNA genetics Drosophila melanogaster genetics Escherichia coli genetics Exons Female Gene Expression Genes, Lethal Genes, Regulator Molecular Sequence Data Mutation Plasmids RNA metabolism RNA Precursors genetics RNA Splicing RNA, Messenger genetics Sex Differentiation Support, Non-U.S. Gov't Trans-Activators genetics metabolism Transcription, Genetic Transfection FBrf0057414 93087158 1454517 1993 01 04 1993 01 04 2002 11 01

0305-1048 20 21 1992 Nov 11 Control of Drosophila Sex-lethal pre-mRNA splicing by its own female-specific product. 5533-40 Drosophila melanogaster somatic sexual differentiation is accomplished by serial function of the products of sex-determination genes. Sex-lethal (Sxl), is one such gene. It is functionally expressed only in female flies. The sex-specific expression of this gene is regulated by alternative mRNA splicing which results in either the inclusion or exclusion of the translation stop codon containing third exon. Although previous genetic and molecular analyses suggest that functional Sxl expression is maintained by a positive feedback loop, where the female-specific Sxl product promotes the synthesis of its own female-specific mRNA, the mechanistic details of such regulation have remained unclear. We have developed a cotransfection system using Drosophila cultured (Kc) cells in which Sxl primary transcripts are expressed with or without the female specific Sxl product. Here we show that the female-specific Sxl product induces the synthesis of its own female-specific mRNA by negative control of male-specific splicing. Deletion, substitution, and binding experiments have demonstrated that multiple uridine-rich sequences in the introns around the male-specific third exon are involved in the splicing regulation of Sxl pre-mRNA. Department of Biophysics, Faculty of Science, Kyoto University, Japan. Sakamoto H H Inoue K K Higuchi I I Ono Y Y Shimura Y Y eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 Insect Hormones 0 Oligodeoxyribonucleotides 0 RNA Precursors 0 Sxl protein, Drosophila 58-96-8 Uridine IM Sxl Animal Base Sequence Drosophila melanogaster Exons Female Insect Hormones genetics metabolism Introns Male Molecular Sequence Data Mutation Oligodeoxyribonucleotides Polymerase Chain Reaction Protein Binding RNA Precursors metabolism RNA Splicing Support, Non-U.S. Gov't Uridine metabolism FBrf0151710 22190659 12202035 2002 08 30 2002 09 24 2002 11 05

0092-8674 110 4 2002 Aug 23 The Drosophila Hox gene deformed sculpts head morphology via direct regulation of the apoptosis activator reaper. 457-66 Hox proteins control morphological diversity along the anterior-posterior body axis of animals, but the cellular processes they directly regulate are poorly understood. We show that during early Drosophila development, the Hox protein Deformed (Dfd) maintains the boundary between the maxillary and mandibular head lobes by activating localized apoptosis. Dfd accomplishes this by directly activating the cell death promoting gene reaper (rpr). One other Hox gene, Abdominal-B (Abd-B), also regulates segment boundaries through the regional activation of apoptosis. Thus, one mechanism used by Drosophila Hox genes to modulate segmental morphology is to regulate programmed cell death, which literally sculpts segments into distinct shapes. This and other emerging evidence suggests that Hox proteins may often regulate the maintenance of segment boundaries. Section of Cell and Developmental Biology, University of California, San Diego, La Jolla 92093, USA. Lohmann Ingrid I McGinnis Nadine N Bodmer Morana M McGinnis William W eng Journal Article

United States Cell 0413066 0 Dfd protein 0 Homeodomain Proteins 0 Peptides 0 reaper peptide, Drosophila IM Animal Apoptosis genetics Body Patterning genetics Cell Differentiation genetics Drosophila melanogaster embryology genetics ultrastructure Gene Expression Regulation, Developmental genetics Genes, Homeobox genetics Head abnormalities physiology Homeodomain Proteins genetics metabolism Lac Operon genetics Microscopy, Electron, Scanning Mutation genetics Peptides genetics metabolism Phenotype Promoter Regions (Genetics) genetics Protein Binding genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics) genetics FBrf0160638 22719038 12835386 2003 07 01 2003 09 30

0950-1991 130 16 2003 Aug Two subunits of the Drosophila mediator complex act together to control cell affinity. 3691-701 The organizing centers for Drosophila imaginal disc development are created at straight boundaries between compartments; these are maintained by differences in cell affinity controlled by selector genes and intercellular signals. skuld and kohtalo encode homologs of TRAP240 and TRAP230, the two largest subunits of the Drosophila mediator complex; mutations in either gene cause identical phenotypes. We show here that both genes are required to establish normal cell affinity differences at the anterior-posterior and dorsal-ventral compartment boundaries of the wing disc. Mutant cells cross from the anterior to the posterior compartment, and can distort the dorsal-ventral boundary in either the dorsal or ventral direction. The Skuld and Kohtalo proteins physically interact in vivo and have synergistic effects when overexpressed, consistent with a skuld kohtalo double-mutant phenotype that is indistinguishable from either single mutant. We suggest that these two subunits do not participate in all of the activities of the mediator complex, but form a submodule that is required to regulate specific target genes, including those that control cell affinity. Skirball Institute of Biomolecular Medicine and Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA. Janody Florence F Martirosyan Zara Z Benlali Aude A Treisman Jessica E JE eng EY 13777 EY NEI GM 56131 GM NIGMS Journal Article

England Development 8701744 0 Drosophila Proteins 0 Eye Proteins 0 Macromolecular Systems 0 PAP protein, Drosophila 0 Protein Subunits 0 kohtalo protein, Drosophila IM Animal Body Patterning Cell Adhesion physiology Drosophila Proteins genetics metabolism Drosophila melanogaster cytology growth & development physiology Eye Proteins genetics metabolism Macromolecular Systems Morphogenesis Phenotype Protein Subunits genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transgenes Wing anatomy & histology growth & development FBrf0051391 90182675 2107028 1990 04 25 1990 04 25 2000 12 18

0092-8674 60 5 1990 Mar 9 Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain. 873-81 The easter gene, required for the development of all lateral and ventral pattern elements in the Drosophila embryo, appears to encode an extracellular serine protease. Dominant easter alleles increase the number of cells that give rise to lateral and ventral structures. We have found that nine dominant and four recessive mutations are caused by single amino acid substitutions at conserved sites in the putative serine protease catalytic domain. The activity of dominant products was assayed by injecting in vitro synthesized transcripts from the dominant alleles into young embryos. The results suggest that the dominant easter products cleave the normal substrate, but fail to respond to a spatially asymmetric regulator. Department of Molecular and Cell Biology, University of California, Berkeley 94720. Jin Y S YS Anderson K V KV eng GM 35437 GM NIGMS Journal Article

UNITED STATES Cell 0413066 0 Oligonucleotide Probes 9007-49-2 DNA EC 3.4.21 Serine Endopeptidases EC 3.4.21.4 Trypsin IM Alleles Amino Acid Sequence Animal Binding Sites Cattle DNA genetics Drosophila melanogaster genetics Female Genes, Dominant Genes, Recessive Genes, Structural Models, Molecular Molecular Sequence Data Mutation Oligonucleotide Probes Polymerase Chain Reaction Protein Conformation Restriction Mapping Sequence Homology, Nucleic Acid Serine Endopeptidases genetics metabolism Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic Trypsin genetics FBrf0040973 84262454 6086453 1984 09 18 1984 09 18 2000 12 18

0016-6731 107 4 1984 Aug Formation of chromosome rearrangements by P factors in Drosophila. 657-78 We studied a collection of 746 chromosome rearrangements all induced by the activity of members of the P family of transposable elements in Drosophila melanogaster. The chromosomes ranged from simple inversions to complex rearrangements. The distribution of complex rearrangement classes was of the kind expected if each rearrangement came about from a single multibreak event followed by random rejoining of chromosome segments, as opposed to a series of two-break events. Most breakpoints occurred at or very near (within a few hundred nucleotide pairs) the sites of preexisting P elements, but these elements were often lost during the rearrangement event. There were also a few cases of apparent gain of P elements. In cases in which both breakpoints of an inversion retained P elements, that inversion was capable of reverting at high frequencies to the original sequence or something close to it. This reversion occurred with sufficient precision to restore the function of a gene, held-up-b, which had been mutated by the breakpoint. However, some of the reversions had acquired irregularities at the former breakpoints that were detectable either by standard cytology or by molecular methods. The revertants themselves retained the ability to undergo further rearrangements depending on the presence of P elements. We interpret these results to rule out the simplest hypotheses of rearrangement formation that involve cointegrate structures or homologous recombination. The data provide a general picture of the rearrangement process and its possible relationship to transposition. Engels W R WR Preston C R CR eng GM 30948 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements IM Animal Chromosomes ultrastructure DNA Transposable Elements Drosophila melanogaster genetics Female Male Models, Genetic Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0055174 92320591 1820687 1992 08 04 1992 08 04 2002 11 01

0168-9525 7 11-12 1991 Nov-Dec Developmental control by the Drosophila EGF receptor homolog DER. 388-92 The identification of receptor tyrosine kinases in Drosophila has provided an opportunity to study the requirement for these proteins during the development of a multicellular organism. Genetic analysis of the function of the Drosophila epidermal growth factor (EGF) receptor homolog (DER) has revealed an extremely diverse set of roles for this protein throughout the life cycle of the organism, for example in eye development and in the establishment of dorsoventral polarity in the oocyte. We discuss the possible basis for the pleiotropic activity of DER, and the similarities and differences in the function of the homologous proteins in other invertebrates and vertebrates. Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel. Shilo B Z BZ Raz E E eng Journal Article Review Review, Tutorial

ENGLAND Trends Genet 8507085 0 Eye Proteins 0 Membrane Glycoproteins 0 epidermal growth factor receptor homolog, Drosophila 0 sevenless protein EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Epidermal Growth Factor IM DER ELp flb let-23 top Animal Cell Polarity Drosophila melanogaster embryology genetics physiology Embryo and Fetal Development Embryo, Nonmammalian enzymology growth & development Eye embryology Eye Proteins physiology Membrane Glycoproteins physiology Oocytes physiology Phenotype Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinase genetics physiology Receptor, Epidermal Growth Factor genetics physiology Sequence Homology, Nucleic Acid Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. 20 FBrf0051384 90150287 2105847 1990 03 28 1990 03 28 2000 12 18

0092-8674 60 4 1990 Feb 23 Functional dissection of Ultrabithorax proteins in D. melanogaster. 597-610 Expression of Ultrabithorax (UBX) proteins via a heat-inducible promoter generated homeotic transformations of segmental identities in the embryonic cuticle and peripheral nervous system (PNS) of Drosophila and transformed antennae into legs in the adult. The embryonic transformations were used to determine the identity functions of members of the UBX family and UBX mutant forms. Whereas UBX forms I and IV each induced the cuticle transformations, only form I induced the PNS transformations. Analysis of the transformations generated by UBX deletions and by a chimeric Ultrabithorax-Antennapedia protein demonstrated that the majority of the UBX identity information is contained within the C-terminal, homeodomain-containing portion of the protein. Implications of these results for how homeotic proteins select particular metameric identities are discussed. Department of Biochemistry, Beckman Center, Stanford University School of Medicine, California 94305. Mann R S RS Hogness D S DS eng Journal Article

UNITED STATES Cell 0413066 0 Heat-Shock Proteins 0 Insect Hormones IM Amino Acid Sequence Animal Drosophila melanogaster anatomy & histology embryology genetics Heat-Shock Proteins genetics Insect Hormones genetics Introns Larva Molecular Sequence Data Phenotype Promoter Regions (Genetics) Protein Conformation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0132340 21100344 11156988 2001 02 22 2001 05 24 2002 11 01

0016-6731 157 2 2001 Feb Molecular identification of virilizer, a gene required for the expression of the sex-determining gene Sex-lethal in Drosophila melanogaster. 679-88 Sex-lethal (Sxl) is a central switch gene in somatic sexual development of Drosophila melanogaster. Female-specific expression of Sxl relies on autoregulatory splicing of Sxl pre-mRNA by SXL protein. This process requires the function of virilizer (vir). Besides its role in Sxl splicing, vir is essential for male and female viability and is also required for the production of eggs capable of embryonic development. We have identified vir molecularly and found that it produces a single transcript of 6 kb that is ubiquitously expressed in male and female embryos throughout development. This transcript encodes a nuclear protein of 210 kD that cannot be assigned to a known protein family. VIR contains a putative transmembrane domain, a coiled-coil region and PEST sequences. We have characterized five different alleles of vir. Those alleles that affect both sexes are associated with large truncations of the protein, while alleles that affect only the female-specific functions are missense mutations that lie relatively close to each other, possibly defining a region important for the regulation of Sxl. Zoological Institute, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Niessen M M Schneiter R R Nothiger R R eng Journal Article

United States Genetics 0374636 0 Membrane Proteins 0 Nuclear Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 Recombinant Fusion Proteins 0 Sxl protein, Drosophila 0 virilizer protein IM Alleles Amino Acid Sequence Animal Blotting, Northern Blotting, Southern Cell Nucleus metabolism Cells, Cultured Drosophila melanogaster genetics Exons Female Gene Library In Situ Hybridization Male Membrane Proteins biosynthesis chemistry genetics Models, Genetic Molecular Sequence Data Mutagenesis Nuclear Proteins biosynthesis chemistry genetics Protein Structure, Tertiary RNA, Messenger metabolism RNA-Binding Proteins chemistry genetics Recombinant Fusion Proteins metabolism Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Sex Determination (Genetics) Support, Non-U.S. Gov't FBrf0051821 90346286 2166702 1990 09 20 1990 09 20 2000 12 18

0890-9369 4 6 1990 Jun Cloning and characterization of the segment polarity gene cubitus interruptus Dominant of Drosophila. 1053-67 The segment polarity mutation, cubitus interruptus Dominant (ciD), of Drosophila melanogaster causes defects in the posterior half of every embryonic segment. We cloned sequences from the ciD region on the proximal fourth chromosome by "tagging" the gene with the transposable element P. Genetic and molecular evidence indicates that the P-element insertions, which all occurred within the same restriction fragment, are in 5'-regulatory regions of the ciD gene within 3 kb of the first exon of its transcript. The putative ciD transcript was identified on the basis of its absence in homozygous ciD embryos. Its spatial pattern of expression during development is unusual in that, unlike most other segmentation genes, it exhibits uniform expression throughout cellular blastoderm and gastrulation and does not resolve into a periodic pattern until the end of the fast phase of germ-band elongation when it is present in 15 broad segmentally repeating stripes along the anterior-posterior axis of the embryo. Registration of the ciD stripes of expression relative to the stripes of other segment polarity genes shows that ciD is expressed in the anterior three-quarters of every segment. This registration does not correlate with the pattern defects observed in ciD mutants. Sequence analysis indicates that the protein encoded by the ciD transcript contains a domain of five tandem amino acid repeats that have sequence similarity to the zinc-finger repeats of the Xenopus transcription factor TFIIIA and that share the highest degree of identity with the human zinc-finger protein GLI, which has been found to be amplified in several human glioblastomas. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208. Orenic T V TV Slusarski D C DC Kroll K L KL Holmgren R A RA eng GENBANK X54360 Journal Article

UNITED STATES Genes Dev 8711660 0 DNA Transposable Elements 0 DNA-Binding Proteins 0 Metalloproteins 7440-66-6 Zinc IM Amino Acid Sequence Animal Base Sequence Blotting, Northern Cloning, Molecular DNA Transposable Elements DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics Gene Expression Genes, Dominant Metalloproteins genetics metabolism Molecular Sequence Data Restriction Mapping Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Zinc metabolism FBrf0128567 20283529 10821764 2000 07 24 2000 07 24 2000 12 18

0950-1991 127 12 2000 Jun The retinal determination gene, dachshund, is required for mushroom body cell differentiation. 2663-72 The dachshund gene of Drosophila encodes a putative transcriptional regulator required for eye and leg development. We show here that dachshund is also required for normal brain development. The mushroom bodies of dachshund mutants exhibit a marked reduction in the number of (&agr;) lobe axons, a disorganization of axons extending into horizontal lobes, and aberrant projections into brain areas normally unoccupied by mushroom body processes. The phenotypes become pronounced during pupariation, suggesting that dachshund function is required during this period. GAL4-mediated expression of dachshund in the mushroom bodies rescues the mushroom body phenotypes. Moreover, dachshund mutant mushroom body clones in an otherwise wild-type brain exhibit the phenotypes, indicating an autonomous role for dachshund. Although eyeless, like dachshund, is preferentially expressed in the mushroom body and is genetically upstream of dachshund for eye development, no interaction of these genes was detected for mushroom body development. Thus, dachshund functions in the developing mushroom body neurons to ensure their proper differentiation. Departments of Molecular and Human Genetics, Molecular and Cellular Biology, Pathology, Psychiatry and Behavioral Sciences and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza 77030, Houston, TX 77030, USA. Martini S R SR Roman G G Meuser S S Mardon G G Davis R L RL eng Journal Article

ENGLAND Development 8701744 0 Nuclear Proteins 0 dachshund protein IM Animal Axons physiology Cell Differentiation Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian cytology physiology Gene Transfer, Horizontal Nerve Fibers physiology Nervous System embryology growth & development Nuclear Proteins genetics metabolism Retina cytology embryology growth & development Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0105474 98447606 9774348 1998 12 10 1998 12 10 2000 12 18

0261-4189 17 20 1998 Oct 15 Analysis of the functional specificity of RS domains in vivo. 6049-60 A number of splicing factors contain extensive regions that are rich in arginine and serine (RS domains). These domains are thought to facilitate protein-protein interactions that are critical in the regulation of alternative splicing. Using a domain swap strategy, we have tested the ability of RS domains from several proteins to substitute in vivo for an essential RS domain in the Drosophila splicing regulator TRA-2. By several criteria, RS domains were found to vary significantly in their ability to support the splicing regulation functions of TRA-2. The RS domain of dU2AF50 functioned efficiently, while that of the dSRp55 protein did not. Moreover, we find similar differences in the ability of RS domains to direct fusion proteins to discrete subnuclear sites at which TRA-2 associates with spermatocyte chromosomes. These results indicate that RS domains are not all functionally equivalent in vivo. Department of Molecular Genetics, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 45, Houston, TX 77030, USA. Dauwalder B B Mattox W W eng CA16672 CA NCI GM50825 GM NIGMS Journal Article

ENGLAND EMBO J 8208664 0 Nerve Tissue Proteins 0 Peptide Fragments 0 Recombinant Fusion Proteins 0 Ribonucleoproteins 0 Transcription Factors 0 fruitless protein 0 transformer-2 protein 56-45-1 Serine 74-79-3 Arginine IM Amino Acid Sequence Amino Acid Substitution genetics Animal Arginine chemistry genetics physiology Drosophila melanogaster Female Male Molecular Sequence Data Nerve Tissue Proteins physiology Peptide Fragments chemistry genetics physiology Recombinant Fusion Proteins genetics physiology Ribonucleoproteins chemistry genetics physiology Serine chemistry genetics physiology Sex Differentiation Spermatocytes chemistry Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors physiology FBrf0108492 99274740 10341239 1999 06 16 1999 06 16 2001 05 18

1529-2401 19 11 1999 Jun 1 Neuroprotection at Drosophila synapses conferred by prior heat shock. 4360-9 Synapses are critical sites of information transfer in the nervous system, and it is important that their functionality be maintained under stressful conditions to prevent communication breakdown. Here we show that synaptic transmission at the Drosophila larval neuromuscular junction is protected by prior exposure to heat shock that strongly induces expression of heat shock proteins, in particular hsp70. Using a macropatch electrode to record synaptic activity at individual, visualized boutons, we found that prior heat shock sustains synaptic performance at high test temperatures through pre- and postsynaptic alterations. After heat shock, nerve impulses release more quantal units at high temperatures and exhibit fewer failures of release (presynaptic modification), whereas the amplitude of quantal currents remains more constant than does that in nonheat-shocked controls (postsynaptic modification). The time course of these physiological changes is similar to that of elevated hsp70. Thus, stress-induced neuroprotective mechanisms maintain function at synapses by modifying their properties. Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. Karunanithi S S Barclay J W JW Robertson R M RM Brown I R IR Atwood H L HL eng Journal Article

UNITED STATES J Neurosci 8102140 0 Heat-Shock Proteins IM Analysis of Variance Animal Drosophila melanogaster physiology Heat Heat-Shock Proteins biosynthesis Larva physiology Nervous System Physiology Quantum Theory Support, Non-U.S. Gov't Synaptic Transmission physiology Time Factors FBrf0064536 94059768 7902124 1994 01 05 1994 01 05 2000 12 18

0925-4773 43 1 1993 Sep A universal target sequence is bound in vitro by diverse homeodomains. 57-70 To determine the number of DNA binding proteins capable of binding a consensus Engrailed binding site, this consensus sequence was used to screen a library of Drosophila cDNA clones in a bacteriophage expression vector. We retrieved clones encoding 20 distinct DNA binding domains, 17 of which are homeodomains. Binding to a variety of oligonucleotides confirms the related sequence specificity of the retrieved binding domains. Nonetheless, the homeodomains have remarkably diverse amino acid sequences. We conclude that during the evolutionary divergence of homeodomains, the specificity of DNA binding has been much more highly conserved than the amino acid sequence. Department of Biochemistry and Biophysics, University of California at San Francisco 94143-0448. Kalionis B B O'Farrell P H PH eng Journal Article

IRELAND Mech Dev 9101218 0 DNA, Complementary 0 DNA, Recombinant 0 DNA-Binding Proteins 0 Insect Hormones 0 Transcription Factors 0 engrail protein, Drosophila IM Antp BarH1 Cfla Dfd Isl-1 Ubx Xlim-1 abd-A abdB ap bk64 ceh-14 cut ems en eve ftz hox2.2 hox2.6 lab lin-11 mec-3 pdm-1 zfh-1 zfh-2 Amino Acid Sequence Animal Base Sequence Binding Sites Comparative Study Consensus Sequence DNA, Complementary genetics metabolism DNA, Recombinant metabolism DNA-Binding Proteins chemistry genetics metabolism Drosophila melanogaster embryology genetics Genes, Homeobox Genes, Structural Genes, Structural, Insect Insect Hormones genetics metabolism Molecular Sequence Data Multigene Family Phylogeny Protein Binding Protein Structure, Tertiary Sequence Alignment Sequence Homology, Amino Acid Species Specificity Substrate Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism FBrf0076455 94364444 8082742 1994 10 12 1994 10 12 2000 12 18

0014-4827 214 1 1994 Sep Transcription of Djun from D. melanogaster is positively regulated by DTF-1, AP-1, and CREB binding sites. 389-99 Djun is the homolog of the mammalian proto-oncogene jun in D. melanogaster, where it encodes a component of an AP-1-like nuclear DNA binding protein, or transcription factor. Djun, unlike its vertebrate counterparts, contains an intron in its 5' noncoding region. The expression of Djun in cultured Schneider line 2 cells is controlled by multiple cis-acting elements in its promoter region and the 5' noncoding region of the transcription unit. A 43-bp 5' upstream promoter region is necessary for the transcription activity of Djun. Deletion of this fragment decreased transcriptional activity by 67-fold. This region includes a TATA box and a sequence similar to the Drosophila transcription factor 1 (DTF-1) consensus sequence (GCAACAT/GC/C). A large DNase I footprint covering both the DTF-1 binding site and the TATA box was detected in this region when incubated with nuclear extract from Drosophila embryos, suggesting interactions with related transcription factors. This 43-bp sequence alone, containing the DTF-1 binding site and TATA box, however, is not sufficient for transcription activity. An 80-bp sequence including the start of transcription has considerable basal activity. An intragenic region containing an AP-1 site and a CRE site modulates or fine tunes activity of the promoter. Its activity as an enhancer is reduced when moved upstream in either orientation. An extragenic region containing two AP-1 sites similarly affects promoter activity. Zoology Department, Arizona State University, Tempe 85287-1501. Wang G L GL Goldstein E S ES eng GENBANK L33044 2 S07 RR07112 RR NCRR Journal Article

UNITED STATES Exp Cell Res 0373226 0 DNA-Binding Protein, Cyclic AMP-Responsive 0 Proto-Oncogene Proteins c-jun 0 Transcription Factors 0 transcription factor 1, Drosophila 9007-49-2 DNA IM Animal Base Sequence DNA metabolism DNA-Binding Protein, Cyclic AMP-Responsive genetics Drosophila melanogaster genetics Gene Expression Regulation Introns genetics Molecular Sequence Data Promoter Regions (Genetics) genetics Protein Binding Proto-Oncogene Proteins c-jun genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics Transcription, Genetic FBrf0050555 90114097 2558282 1990 02 22 1990 02 22 2000 12 18

0026-8925 220 1 1989 Dec Novel genes influencing the expression of the yellow locus and mdg4 (gypsy) in Drosophila melanogaster. 121-6 We used a system with a mobilized Stalker transposable element, sometimes in combination with P-M hybrid dysgenesis, in the search for new mutations interfering with the y2 mutation induced by mdg4 (gypsy) insertion into the yellow locus. A novel gene, modifier of mdg4, was detected in chromosome 3. The mutation mod(mdg4) either enhanced or suppressed phenotypic changes in different mutations induced by mdg4 insertions. Thus, mod(mdg4) seems to be involved in the control of mdg4 expression. Six other loci designated as enhancers of yellow were also detected. The e(y)n (with n from 1-6) mutations enhanced the expression of several y mutations induced by different insertions into the yellow locus. The major change is a damage of bristle and hair pigmentation which is not suppressed by su(Hw) mutations. On the other hand, e(y)n alleles do not interact with mdg4 induced mutations in other loci. All e(y)n genes are located in different regions of the X chromosome. One may speculate that e(y)n genes are involved in trans-regulation of the yellow locus and possibly of some other loci. N.I. Vavilov Institute of General Genetics, USSR Academy of Sciences, Moscow. Georgiev P G PG Gerasimova T I TI eng Journal Article

GERMANY, WEST Mol Gen Genet 0125036 0 DNA Transposable Elements IM Alleles Animal DNA Transposable Elements Drosophila melanogaster genetics Gene Expression Regulation Mutation Phenotype Pigmentation genetics FBrf0132350 21068701 11156616 2001 01 26 2001 03 01 2003 06 16

1088-9051 11 1 2001 Jan Identification of new X-chromosomal genes required for Drosophila oogenesis and novel roles for fs(1)Yb, brainiac and dunce. 67-77 We performed a screen for female sterile mutations on the X chromosome of Drosophila melanogaster and identified new loci required for developmental events in oogenesis as well as new alleles of previously described genes. We present mapping and phenotypic characterization data for many of these genes and discuss their significance in understanding fundamental developmental and cell biological processes. Our screen has identified genes that are involved in cell cycle control, intracellular transport, cell migration, maintenance of cell membranes, epithelial monolayer integrity and cell survival or apoptosis. We also describe new roles for the genes dunce (dnc), brainiac (brn) and fs(1)Yb, and we identify new alleles of Sex lethal (Sxl), ovarian tumor (otu), sans filles (snf), fs(1)K10, singed (sn), and defective chorion-1 (dec-1). Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada. Swan A A Hijal S S Hilfiker A A Suter B B eng Journal Article

United States Genome Res 9518021 0 Genetic Markers 0 Insect Proteins 0 Membrane Proteins 0 brainiac protein 0 fs(1)Yb protein, Drosophila IM Animal Apoptosis genetics Body Patterning genetics Drosophila melanogaster genetics physiology Female Gene Expression Regulation, Developmental Genes, Structural, Insect Genetic Markers Insect Proteins physiology Male Membrane Proteins physiology Mutation Oogenesis genetics Support, Non-U.S. Gov't X Chromosome genetics FBrf0098751 97476316 9335602 1997 12 08 1997 12 08 2003 06 16

0016-6731 147 2 1997 Oct Enhancement of overgrowth by gene interactions in lethal(2)giant discs imaginal discs from Drosophila melanogaster. 657-70 Recessive lethal mutations of the lethal(2)giant discs (l(2)gd) and lethal(2)fat (l(2)ft) loci of Drosophila melanogaster cause imaginal disc hyperplasia during a prolonged larval stage. Imaginal discs from l(2)ft l(2)gd or Gl(2)gd double homozygotes show more extensive overgrowth than in either single homozygote, and double homozygous l(2)ft l(2)gd mitotic clones in adult flies show much more overgrowth than is seen in clones homozygous for either l(2)gd or l(2)ft alone. dachsous (ds) also acts as an enhancer of l(2)gd, producing dramatically overgrown discs and causing failure to pupariate in double homozygotes. The comb gap (cg) mutation, which also interacts with ds, greatly enhances the tendency of imaginal discs from l(2)gd larvae to duplicate as they overgrow. If l(2)gd homozygotes are made heterozygous for l(2)ft, then several discs duplicate, indicating that l(2)ft acts an a dominant enhancer of l(2)gd. l(2)ft also acts as a dominant enhancer of l(2)gd, and conversely l(2)gd acts as a dominant modifier of l(2)ft. The enhancement of overgrowth caused by various mutant combinations is accompanied by changes in expression of Decapentaplegic and Wingless. These results show that tumor suppressor genes act in combination to control cell proliferation, and that tissue hyperplasia can be associated with ectopic expression of genes involved in pattern formation. Developmental Biology Center, University of California, Irvine 92717, USA. m.buratovich@sussex.ac.uk Buratovich M A MA Bryant P J PJ eng HD-27173 HD NICHD Journal Article

UNITED STATES Genetics 0374636 0 Insect Proteins 0 lethal (2) giant larvae protein, Drosophila IM Animal Body Patterning genetics Drosophila melanogaster genetics growth & development Enhancer Elements (Genetics) Homozygote Insect Proteins genetics Phenotype Support, U.S. Gov't, P.H.S. FBrf0138357 21417202 11526072 2001 08 29 2001 10 11 2002 11 08

0950-1991 128 14 2001 Jul The sex determination master switch, Sex-lethal, responds to Hedgehog signaling in the Drosophila germline. 2649-60 Sex-lethal is the Drosophila melanogaster sex determination master switch. It is also required in female germ cells to control mitosis and meiotic recombination. As early germ cells mature, distinct changes in both Sex-lethal protein levels and localization occur. By manipulating the levels of Hedgehog and making germline clones of components in the hedgehog signaling pathway, we demonstrate that Hedgehog affects the nuclear translocation of Sex-lethal and the levels of the protein in early germ cells. This effect is mediated primarily through degradation. Consistent with the Hedgehog pathway regulating Sex-lethal, we find Sex-lethal in a complex with Fused and Costal-2, both downstream components of the pathway. This is the first demonstration that downstream components of the Hedgehog signaling pathway regulate a target other than Cubitus interruptus. Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, Alabama 35294, USA. Vied C C Horabin J I JI eng Journal Article

England Development 8701744 0 Insect Proteins 0 Membrane Proteins 0 RNA-Binding Proteins 0 Receptors, Cell Surface 0 Repressor Proteins 0 Sxl protein, Drosophila 0 Tubulin 0 costal2 protein 0 patched protein, Drosophila 0 smoothened protein 0 suppressor of fused protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 3.6.1.- Kinesin IM Animal Cell Survival Cyclic AMP-Dependent Protein Kinases metabolism Cytoplasm metabolism Drosophila melanogaster genetics metabolism Female Gene Expression Germ Cells Insect Proteins genetics metabolism Kinesin genetics Membrane Proteins genetics Protein-Serine-Threonine Kinases genetics metabolism RNA-Binding Proteins genetics metabolism Receptors, Cell Surface genetics metabolism Repressor Proteins metabolism Sex Determination (Genetics) Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tubulin genetics FBrf0144849 21856316 11867535 2002 02 27 2002 05 14 2002 11 01

0261-4189 21 5 2002 Mar 1 Drosophila Gp150 is required for early ommatidial development through modulation of Notch signaling. 1074-83 Cellular signaling activities must be tightly regulated for proper cell fate control and tissue morphogenesis. Here we report that the Drosophila leucine-rich repeat transmembrane glycoprotein Gp150 is required for viability, fertility and development of the eye, wing and sensory organs. In the eye, Gp150 plays a critical role in regulating early ommatidial formation. Gp150 is highly expressed in cells of the morphogenetic furrow (MF) region, where it accumulates exclusively in intracellular vesicles in an endocytosis-independent manner. Loss of gp150 function causes defects in the refinement of photoreceptor R8 cells and recruitment of other cells, which leads to the formation of aberrant ommatidia. Genetic analyses suggest that Gp150 functions to modulate Notch signaling. Consistent with this notion, Gp150 is co-localized with Delta in intracellular vesicles in cells within the MF region and loss of gp150 function causes accumulation of intracellular Delta protein. Therefore, Gp150 might function in intracellular vesicles to modulate Delta-Notch signaling for cell fate control and tissue morphogenesis. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. Fetchko Michael M Huang Wei W Li Ying Y Lai Zhi-Chun ZC eng Journal Article

England EMBO J 8208664 0 DNA Transposable Elements 0 Drosophila Proteins 0 Eye Proteins 0 Gp150, insect 0 Insect Hormones 0 Membrane Glycoproteins 0 Membrane Proteins 0 Recombinant Fusion Proteins 0 delta protein 0 notch protein EC 3.6.1.- GTP Phosphohydrolases EC 3.6.1.50 Dynamins IM Animal Animal Structures growth & development Cells, Cultured Chromosome Mapping DNA Transposable Elements genetics Drosophila Proteins genetics physiology Drosophila melanogaster cytology genetics growth & development Dynamins Eye growth & development Eye Proteins genetics physiology Fertility genetics GTP Phosphohydrolases physiology Gene Expression Regulation, Developmental Genes, Lethal Genes, Structural, Insect Infertility genetics Insect Hormones genetics physiology Membrane Glycoproteins genetics physiology Membrane Proteins genetics physiology Morphogenesis Photoreceptors, Invertebrate metabolism Recombinant Fusion Proteins physiology Sense Organs growth & development Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection Wing growth & development FBrf0049823 89252821 2542128 1989 07 10 1989 07 10 2000 12 18

0890-9369 3 4 1989 Apr Alteration of hsp82 gene expression by the gypsy transposon and suppressor genes in Drosophila melanogaster. 454-68 Several mutations in Drosophila result from insertion of the gypsy retrotransposon. Gypsy insertion mutagenesis and its modulation by allele-specific modifier genes were investigated by inserting gypsy or fragments of it into the intron of the Drosophila hsp82 heat shock gene. With gypsy in the parallel orientation, nearly all transcripts in transfected cells and transformed pupae were truncated in the 5' long terminal repeat (LTR). Truncation also occurred in or near the 3' LTR. The 5' LTR polyadenylation signal was strongly potentiated by a downstream 326-bp internal gypsy segment in either orientation. Anti-parallel gypsy reduced the amount of normal transcript to a much smaller extent, and a low level of truncation occurred within gypsy. No evidence was found for effects of the gypsy insertions on the hsp82 promoter. Mutations in the allelespecific modifier genes su(f) and su(w alpha) had effects on the amounts of readthrough transcripts consistent with their genetic behavior, whereas the effects of mutations in su(Hw) were only partly in accord with genetic expectations. Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138. Dorsett D D Viglianti G A GA Rutledge B J BJ Meselson M M eng Journal Article

UNITED STATES Genes Dev 8711660 0 DNA Transposable Elements 0 Heat-Shock Proteins 0 Plasmids EC 3.1.- Endonucleases EC 3.1.30.1 Aspergillus Nuclease S1 IM Animal Aspergillus Nuclease S1 Blotting, Northern Chromosome Mapping DNA Transposable Elements Drosophila melanogaster genetics Endonucleases analysis Gene Expression Regulation Heat-Shock Proteins genetics Introns Mutation Plasmids Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Transcription, Genetic Transfection Transformation, Genetic FBrf0123218 20096717 10629220 2000 03 09 2000 03 09 2003 06 16

0021-9525 148 1 2000 Jan 10 Regulation of actin filament cross-linking and bundle shape in Drosophila bristles. 87-100 Previous studies demonstrate that in developing Drosophila bristles, two cross-linking proteins are required sequentially to bundle the actin filaments that support elongating bristle cells. The forked protein initiates the process and facilitates subsequent cross-linking by fascin. Using cross-linker-specific antibodies, mutants, and drugs we show that fascin and actin are present in excessive amounts throughout bundle elongation. In contrast, the forked cross-linker is limited throughout bundle formation, and accordingly, regulates bundle size and shape. We also show that regulation of cross-linking by phosphorylation can affect bundle size. Specifically, inhibition of phosphorylation by staurosporine results in a failure to form large bundles if added during bundle formation, and leads to a loss of cross-linking by fascin if added after the bundles form. Interestingly, inhibition of dephosphorylation by okadaic acid results in the separation of the actin bundles from the plasma membrane. We further show by thin section electron microscopy analysis of mutant and wild-type bristles that the amount of material that connects the actin bundles to the plasma membrane is also limited throughout bristle elongation. Therefore, overall bundle shape is determined by the number of actin filaments assembled onto the limited area provided by the connector material. We conclude that assembly of actin bundles in Drosophila bristles is controlled in part by the controlled availability of a single cross-linking protein, forked, and in part by controlled phosphorylation of cross-links and membrane actin connector proteins. Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. Tilney L G LG Connelly P S PS Vranich K A KA Shaw M K MK Guild G M GM eng GM-52857 GM NIGMS Journal Article

UNITED STATES J Cell Biol 0375356 0 Actins 0 Carrier Proteins 0 Cross-Linking Reagents 0 Enzyme Inhibitors 0 Insect Proteins 0 Microfilament Proteins 0 forked protein, Drosophila 146808-54-0 fascin 62996-74-1 Staurosporine 78111-17-8 Okadaic Acid IM Actins metabolism Animal Carrier Proteins metabolism Cell Membrane metabolism ultrastructure Cross-Linking Reagents Drosophila melanogaster metabolism ultrastructure Enzyme Inhibitors pharmacology Insect Proteins metabolism Microfilament Proteins metabolism Microfilaments metabolism Okadaic Acid pharmacology Phosphorylation Staurosporine pharmacology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Time Factors FBrf0137253 21347569 11454766 2001 07 16 2001 11 01 2003 06 16

0016-6731 158 3 2001 Jul An interaction type of genetic screen reveals a role of the Rab11 gene in oskar mRNA localization in the developing Drosophila melanogaster oocyte. 1177-88 Abdomen and germ cell development of Drosophila melanogaster embryo requires proper localization of oskar mRNA to the posterior pole of the developing oocyte. oskar mRNA localization depends on complex cell biological events like cell-cell communication, dynamic rearrangement of the microtubule network, and function of the actin cytoskeleton of the oocyte. To investigate the cellular mechanisms involved, we developed a novel interaction type of genetic screen by which we isolated 14 dominant enhancers of a sensitized genetic background composed of mutations in oskar and in TropomyosinII, an actin binding protein. Here we describe the detailed analysis of two allelic modifiers that identify Drosophila Rab11, a gene encoding small monomeric GTPase. We demonstrate that mutation of the Rab11 gene, involved in various vesicle transport processes, results in ectopic localization of oskar mRNA, whereas localization of gurken and bicoid mRNAs and signaling between the oocyte and the somatic follicle cells are unaffected. We show that the ectopic oskar mRNA localization in the Rab11 mutants is a consequence of an abnormally polarized oocyte microtubule cytoskeleton. Our results indicate that the internal membranous structures play an important role in the microtubule organization in the Drosophila oocyte and, thus, in oskar RNA localization. Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, H-6701 POB 521 Szeged, Hungary. Jankovics F F Sinka R R Erdélyi M M eng Journal Article

United States Genetics 0374636 0 Insect Proteins 0 RNA, Messenger 0 oskar protein, Drosophila 0 rab11 protein EC 3.6.1.- rab GTP-Binding Proteins IM Animal Drosophila melanogaster genetics Female Genetic Complementation Test Genetic Screening In Situ Hybridization Insect Proteins genetics Male Mutation Oocytes metabolism Phenotype RNA, Messenger genetics metabolism Support, Non-U.S. Gov't rab GTP-Binding Proteins genetics FBrf0132450 20581355 11141565 2001 01 09 2001 01 25 2003 06 16

0036-8075 291 5501 2001 Jan 5 Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. 131-3 Directed cell migration is important for many aspects of normal animal development, but little is known about how cell migrations are guided or the mechanisms by which guidance cues are translated into directed cell movement. Here we present evidence that signaling mediated by the epidermal growth factor receptor (EGFR) guides dorsal migration of border cells during Drosophila oogenesis. The transforming growth factor-alpha (TGF-alpha)-like ligand Gurken appears to serve as the guidance cue. To mediate this guidance function, EGFR signals via a pathway that is independent of Raf-MAP kinase and receptor-specific. Developmental Biology Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany. Duchek P P Rørth P P eng Journal Article

UNITED STATES Science 0404511 0 Insect Proteins 0 Ligands 0 MAP Kinase Signaling System 0 gurken protein, Drosophila 182299-68-9 vein protein, Drosophila 76057-06-2 Transforming Growth Factors EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Animal Cell Movement Drosophila melanogaster cytology genetics physiology Female Insect Proteins genetics physiology Ligands MAP Kinase Signaling System Mitogen-Activated Protein Kinases metabolism Mutation Oocytes cytology physiology Oogenesis Ovarian Follicle cytology physiology Proto-Oncogene Proteins c-raf metabolism Receptor, Epidermal Growth Factor genetics physiology Signal Transduction Transforming Growth Factors genetics physiology FBrf0111771 20042290 10572045 2000 01 21 2000 01 21 2003 03 28

0950-1991 126 24 1999 Dec Wingless and Hedgehog pattern Drosophila denticle belts by regulating the production of short-range signals. 5689-98 The secreted proteins Wingless and Hedgehog are essential to the elaboration of the denticle pattern in the epidermis of Drosophila embryos. We show that signaling by Wingless and Hedgehog regulates the expression of veinlet (rhomboid) and Serrate, two genes expressed in prospective denticle belts. Thus, Serrate and veinlet (rhom) partake in the last layer of the segmentation cascade. Ultimately, Wingless, Hedgehog, Veinlet (an indirect activator of the Egfr) and Serrate (an activator of Notch) are expressed in non-overlapping narrow stripes. The interface between any two stripes allows a reliable prediction of individual denticle types and polarity suggesting that contact-dependent signaling modulates individual cell fates. Attributes of a morphogen can be ascribed to Hedgehog in this system. However, no single morphogen organises the whole denticle pattern. National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Alexandre C C Lecourtois M M Vincent J J eng Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 Rho protein, Drosophila 0 rho-2 protein, Drosophila 117758-26-6 wingless protein, Drosophila 134324-36-0 Serrate protein 149291-21-4 hedgehog protein, Drosophila IM Animal Body Patterning Drosophila melanogaster embryology Gene Expression Regulation, Developmental Insect Proteins genetics Membrane Proteins genetics Proto-Oncogene Proteins genetics Signal Transduction Support, Non-U.S. Gov't FBrf0155683 22474014 12586061 2003 02 14 2003 03 14 2003 06 16

1534-5807 4 2 2003 Feb A gradient of JAK pathway activity patterns the anterior-posterior axis of the follicular epithelium. 167-77 The Drosophila egg develops through closely coordinated activities of associated germline and somatic cells. An essential aspect of egg development is the differentiation of the somatic follicle cells into several distinct subpopulations with specific functions. Here we demonstrate that the graded activity of the Janus kinase (JAK) pathway, stimulated by the Unpaired ligand, patterns the anterior-posterior axis of the follicular epithelium. Different levels of JAK activity instruct adoption of distinct anterior cell fates. Further, the coordinated activities of the JAK/STAT and epidermal growth factor receptor (EGFR) pathways are required to specify the posterior terminal cell fate. We propose that Upd secreted from the polar cells may act as a morphogen to stimulate A/P-derived follicular fates through JAK pathway activation. University of Kentucky, Department of Biology, 101 Morgan Building, Lexington, KY 40506, USA. Xi Rongwen R McGregor Jennifer R JR Harrison Douglas A DA eng Journal Article

United States Dev Cell 101120028 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Glycoproteins 0 Stat3 protein 0 Trans-Activators 0 outstretched protein, Drosophila EC 2.7.1.- Janus kinase 1 EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Animals, Genetically Modified Cell Differentiation Cell Polarity DNA-Binding Proteins metabolism Drosophila Proteins metabolism Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Enzyme Activation Epithelial Cells cytology Female Gene Expression Regulation, Developmental Glycoproteins metabolism Mutation Oogenesis physiology Ovarian Follicle cytology physiology Phenotype Protein-Tyrosine Kinase metabolism Receptor, Epidermal Growth Factor metabolism Signal Transduction physiology Support, U.S. Gov't, Non-P.H.S. Trans-Activators metabolism FBrf0151440 22144534 12134162 2002 07 31 2002 09 11 2002 11 01

1465-7392 4 8 2002 Aug Myosin VI is required for E-cadherin-mediated border cell migration. 616-20 Myosin VI (MyoVI) is a pointed-end-directed, actin-based motor protein, and mutations in the gene result in disorganization of hair cell stereocilia and cause deafness in mice. MyoVI also localizes to the leading edges of growth-factor-stimulated fibroblast cells and has been suggested to be involved in cell motility. There has been no direct test of this hypothesis, however. Drosophila melanogaster MyoVI is expressed in a small group of migratory follicle cells, known as border cells. Here we show that depletion of MyoVI specifically from border cells severely inhibited their migration. Similar to MyoVI, E-cadherin is required for border cell migration. We found that E-cadherin and Armadillo (Arm, Drosophila beta-catenin) protein levels were specifically reduced in cells lacking MyoVI, whereas other proteins were not. In addition, MyoVI protein levels were reduced in cells lacking DE-cadherin or Arm. MyoVI and Arm co-immunoprecipitated from ovarian protein extracts. These data suggest that MyoVI is required for border cell migration where it stabilizes E-cadherin and Arm. Mutations in MyoVIIA, another unconventional myosin protein, also lead to deafness, and MyoVIIA interacts with E-cadherin through a membrane protein called vezatin. Multiple biochemical mechanisms may exist, therefore, for cadherins to associate with diverse unconventional myosins that are required for normal stereocilium formation or maintenance. Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA. Geisbrecht Erika R ER Montell Denise J DJ eng GM46425 GM NIGMS Journal Article

England Nat Cell Biol 100890575 0 Cadherins 0 Cytoskeletal Proteins 0 Drosophila Proteins 0 Insect Proteins 0 Molecular Motors 0 Myosin Heavy Chains 0 Trans-Activators 0 armadillo protein, Drosophila 0 myosin VI 146409-33-8 beta catenin IM Nat Cell Biol. 2002 Sep;4(9):E211-2 12205482 Animal Animals, Genetically Modified Cadherins metabolism Cell Movement physiology Cytoskeletal Proteins metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster cytology genetics metabolism Female Insect Proteins metabolism Molecular Motors genetics metabolism Mutation Myosin Heavy Chains genetics metabolism Ovary cytology metabolism Support, U.S. Gov't, P.H.S. Trans-Activators metabolism FBrf0128151 20337990 10882142 2000 07 17 2000 07 17 2003 06 16

1097-2765 5 3 2000 Mar The JAK/STAT signaling pathway is required for the initial choice of sexual identity in Drosophila melanogaster. 581-7 The choice of sexual identity in Drosophila is determined by a system that measures the X chromosome to autosome ratio (X/A). This system depends upon unequal expression of X-linked numerator genes in 1X and 2X nuclei. The numerators activate a special Sxl promoter, Sxl-Pe, in 2X/2A nuclei, but not 1X/2A nuclei. By multimerizing a conserved Sxl-Pe sequence block, we generated a gain-of-function promoter, Sxl-PeGOF, that is inappropriately active in 1X/2A nuclei. GOF activity requires the X-linked unpaired (upd) gene, which encodes a ligand for the Drosophila JAK/STAT signaling pathway. upd also functions as a numerator element in regulating wild-type Sxl-Pe reporters. We demonstrate that the JAK kinase, Hopscotch, and the STAT DNA-binding protein, Marelle, are also required for Sxl-Pe activation. Department of Molecular Biology, Princeton University, New Jersey 08544, USA. Jinks T M TM Polydorides A D AD Calhoun G G Schedl P P eng Journal Article

UNITED STATES Mol Cell 9802571 0 DNA-Binding Proteins 0 Glycoproteins 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 0 Trans-Activators 0 outstretched protein, Drosophila EC 2.7.1.- Hop protein EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.1.37 Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Amino Acid Sequence Animal Conserved Sequence DNA-Binding Proteins metabolism Drosophila melanogaster embryology genetics Female Glycoproteins metabolism Mitogen-Activated Protein Kinases metabolism Promoter Regions (Genetics) Protein Kinases metabolism Protein-Tyrosine Kinase metabolism RNA-Binding Proteins metabolism Repetitive Sequences, Amino Acid Sex Determination (Genetics) Signal Transduction Support, U.S. Gov't, P.H.S. Trans-Activators metabolism FBrf0105854 98453411 9778511 1999 01 19 1999 01 19 2002 04 19

0950-1991 125 22 1998 Nov Cis-interactions between Delta and Notch modulate neurogenic signalling in Drosophila. 4531-40 We find that ectopic expression of Delta or Serrate in neurons within developing bristle organs is capable of non-autonomously inducing the transformation of the pre-trichogen cell into a tormogen cell in a wide variety of developmental contexts. The frequencies at which Delta can induce these transformations are dependent on the level of ectopic Delta expression and the levels of endogenous Notch signalling pathway components. The pre-trichogen cell becomes more responsive to Delta- or Serrate-mediated transformation when the level of endogenous Delta is reduced and less responsive when the dosage of endogenous Delta is increased, supporting the hypothesis that Delta interferes autonomously with the ability of a cell to receive either signal. We also find that a dominant-negative form of Notch, ECN, is capable of autonomously interfering with the ability of a cell to generate the Delta signal. When the region of Notch that mediates trans-interactions between Delta and the Notch extracellular domain is removed from ECN, the ability of Delta to signal is restored. Our findings imply that cell-autonomous interactions between Delta and Notch can affect the ability of a cell to generate and to transduce a Delta-mediated signal. Finally, we present evidence that the Fringe protein can interfere with Delta- and Serrate-mediated signalling within developing bristle organs, in contrast to previous reports of the converse effects of Fringe on Delta signalling in the developing wing. Program in Genetics, Cell and Developmental Biology, Department of Biology, Indiana University, Bloomington, Indiana, USA. Jacobsen T L TL Brennan K K Arias A M AM Muskavitch M A MA eng GM33291 GM NIGMS NO1-HD-7-3263 HD NICHD Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Membrane Proteins 0 delta protein 0 notch protein 134324-36-0 Serrate protein EC 2.4.- fringe protein IM Animal Cell Differentiation Drosophila melanogaster cytology Insect Proteins metabolism Membrane Proteins metabolism Nervous System cytology Neurons Sense Organs cytology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Thorax embryology FBrf0051953 90337297 2116356 1990 09 12 1990 09 12 2000 12 18

0016-6731 125 3 1990 Jul Genetic evidence that the ovo locus is involved in Drosophila germ line sex determination. 535-50 Zygotically contributed ovo gene product is required for the survival of female germ cells in Drosophila melanogaster. Trans-allelic combinations of weak and dominant ovo mutations (ovoD) result in viable germ cells that appear to be partially transformed from female to male sexual identity. The ovoD2 mutation is partially suppressed by many Sex-lethal alleles that affect the soma, while those that affect only the germ line fail to interact with ovoD2. One of two loss-of-function ovo alleles is suppressed by a loss-of-function Sex-lethal allele. Because ovo mutations are germ line dependent, it is likely that ovo is suppressed by way of communication between the somatic and germ lines. A loss-of-function allele of ovo is epistatic to germ line dependent mutations in Sex-lethal. The germ line dependent sex determination mutation, sans fille, and ovoD mutations show a dominant synergistic interaction resulting in partial transformation of germ line sexual identity. The ovo locus appears to be involved in germ line sex determination and is linked in some manner to sex determination in the soma. Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. Oliver B B Pauli D D Mahowald A P AP eng HD-17608 HD NICHD T32-HD07104 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Genetics 1990 Oct;126(2):477 Alleles Animal Drosophila melanogaster genetics Female Genes Germ Cells physiology Male Mutation Phenotype Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0068431 94170388 8124723 1994 04 12 1994 04 12 2001 03 23

0092-8674 76 5 1994 Mar 11 A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways. 875-88 In the Drosophila eye, activation of the sevenless (sev) receptor tyrosine kinase is required for the specification of the R7 photoreceptor cell fate. In a genetic screen for mutations that result in the activation of the sev signaling pathway in the absence of the inducing signal, we identified a gain-of-function mutation in rolled (rlSevenmaker [rlSem]), which encodes a homolog of mitogen-activated protein (MAP) kinase. In addition to the sev pathway, this mutation activates the pathways controlled by torso and the epidermal growth factor receptor homology. The rlSem mutation results in the substitution of a single conserved amino acid in the kinase domain. Activation of MAP kinase by the rlSem mutation is both necessary and sufficient to activate multiple signaling pathways controlled by receptor tyrosine kinases. Zoologisches Institut, Universität Zürich, Switzerland. Brunner D D Oellers N N Szabad J J Biggs W H WH 3rd Zipursky S L SL Hafen E E eng GENBANK M95124 Journal Article

UNITED STATES Cell 0413066 0 DNA Primers 0 Proto-Oncogene Proteins EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Drk ERK-1 ERK-2 FUS3 KSS1 MPK1 Raf Ras1 Sos Alleles Amino Acid Sequence Animal Base Sequence Ca(2+)-Calmodulin Dependent Protein Kinase genetics metabolism Comparative Study DNA Primers chemistry Drosophila melanogaster embryology enzymology Enzyme Activation Genes, Dominant Genes, ras Molecular Sequence Data Mutation Proto-Oncogene Proteins physiology Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases metabolism Sequence Alignment Sequence Homology, Amino Acid Signal Transduction Structure-Activity Relationship Support, Non-U.S. Gov't FBrf0151948 22328942 12441298 2002 11 20 2003 02 04 2003 06 16

0950-1991 130 1 2003 Jan Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium. 135-45 Rearrangement of cells constrained within an epithelium is a key process that contributes to tubular morphogenesis. We show that activation in a gradient of the highly conserved JAK/STAT pathway is essential for orienting the cell rearrangement that drives elongation of a genetically tractable model. Using loss-of-function and gain-of-function experiments, we show that the components of the pathway from ligand to the activated transcriptional regulator STAT are required for cell rearrangement in the Drosophila embryonic hindgut. The difference in effect between localized expression of ligand (Unpaired) and dominant active JAK (Hopscotch) demonstrates that the ligand plays a cell non-autonomous role in hindgut cell rearrangement. Taken together with the appearance of STAT92E in a gradient in the hindgut epithelium, these results support a model in which an anteroposterior gradient of ligand results in a gradient of activated STAT. These results provide the first example in which JAK/STAT signaling plays a required role in orienting cell rearrangement that elongates an epithelium. Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095-1606, USA. Johansen Katherine A KA Iwaki D David DD Lengyel Judith A JA eng GM07104 GM NIGMS GM07185 GM NIGMS HD09948 HD NICHD Journal Article

England Development 8701744 0 Carrier Proteins 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Glycoproteins 0 Receptors, Interleukin 0 STAT92E protein 0 Trans-Activators 0 domeless protein, Drosophila 0 drumstick protein, Drosophila 0 outstretched protein, Drosophila EC 2.7.1.- Hop protein EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal Body Patterning genetics Carrier Proteins genetics metabolism DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics Embryo, Nonmammalian Embryonic Induction physiology Epithelial Cells metabolism Epithelium embryology metabolism Gastrointestinal System cytology embryology Gene Expression Regulation, Developmental Glycoproteins genetics metabolism Intestine, Large cytology embryology metabolism Mutation Protein-Tyrosine Kinase genetics metabolism Receptors, Interleukin genetics metabolism Signal Transduction Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism FBrf0151843 22213268 12225672 2002 09 12 2003 06 16

0960-9822 12 17 2002 Sep 3 Posterior localization of dynein and dorsal-ventral axis formation depend on kinesin in Drosophila oocytes. 1541-5 To establish the major body axes, late Drosophila oocytes localize determinants to discrete cortical positions: bicoid mRNA to the anterior cortex, oskar mRNA to the posterior cortex, and gurken mRNA to the margin of the anterior cortex adjacent to the oocyte nucleus (the "anterodorsal corner"). These localizations depend on microtubules that are thought to be organized such that plus end-directed motors can move cargoes, like oskar, away from the anterior/lateral surfaces and hence toward the posterior pole. Likewise, minus end-directed motors may move cargoes toward anterior destinations. Contradicting this, cytoplasmic dynein, a minus-end motor, accumulates at the posterior. Here, we report that disruption of the plus-end motor kinesin I causes a shift of dynein from posterior to anterior. This provides an explanation for the dynein paradox, suggesting that dynein is moved as a cargo toward the posterior pole by kinesin-generated forces. However, other results present a new transport polarity puzzle. Disruption of kinesin I causes partial defects in anterior positioning of the nucleus and severe defects in anterodorsal localization of gurken mRNA. Kinesin may generate anterodorsal forces directly, despite the apparent preponderance of minus ends at the anterior cortex. Alternatively, kinesin I may facilitate cytoplasmic dynein-based anterodorsal forces by repositioning dynein toward microtubule plus ends. Department of Biology, Indiana University, Bloomington 47405, USA. Brendza Robert P RP Serbus Laura R LR Saxton William M WM Duffy Joseph B JB eng GM46295 GM NIGMS Journal Article

England Curr Biol 9107782 0 Drosophila Proteins 0 Egg Proteins 0 Homeodomain Proteins 0 Molecular Motors 0 RNA, Messenger 0 Trans-Activators 0 Transforming Growth Factor alpha 0 bicoid protein, Drosophila 0 gurken protein, Drosophila 0 oskar protein, Drosophila 76057-06-2 Transforming Growth Factors EC 3.6.1.- Kinesin EC 3.6.1.33 Dynein ATPase IM Animal Cell Polarity Drosophila Proteins metabolism physiology Drosophila melanogaster metabolism ultrastructure Dynein ATPase metabolism Egg Proteins physiology Homeodomain Proteins metabolism Kinesin physiology Microscopy, Electron Microtubules physiology Molecular Motors Morphogenesis genetics Oocytes metabolism ultrastructure Protein Transport RNA, Messenger metabolism Support, U.S. Gov't, P.H.S. Trans-Activators metabolism Transforming Growth Factor alpha metabolism Transforming Growth Factors metabolism FBrf0091115 97132587 8978039 1997 03 31 1997 03 31 2000 12 18

0016-6731 144 4 1996 Dec Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. 1497-510 Previously, we mapped quantitative trait loci (QTL) affecting response to short-term selection for abdominal bristle number to seven suggestive regions that contain loci involved in bristle development and/or that have adult bristle number mutant phenotypes, and are thus candidates for bristle number QTL in natural populations. To test the hypothesis that the factors contributing to selection response genetically interact with these candidate loci, high and low chromosomes from selection lines were crossed to chromosomes containing wild-type or mutant alleles at the candidate loci, and the numbers of bristles were recorded in trans heterozygotes. Quantitative failure to complement, detected as a significant selection line*cross effect by analysis of variance, can be interpreted as evidence for allelism or epistasis between the factors on selected chromosomes and the candidate loci. Mutations at some candidate loci (bb, emc, h, Dl, Hairless) showed strong interactions with selected chromosomes, whereas others interacted weakly (ASC, abd, Scr) or not at all (N, mab, E(spl)). These results support the hypothesis that some candidate loci, initially identified through mutations of large effect on bristle number, either harbor or are close members in the same genetic pathway as variants that contribute to standing variation in bristle number. Center for Population Biology, University of California, Davis 95616, USA. tdlong@ucdavis.edu Long A D AD Mullaney S L SL Mackay T F TF Langley C H CH eng GM-45146 GM NIGMS GM-45344 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Chromosome Mapping Drosophila melanogaster genetics Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0104744 98441472 9768358 1999 02 01 1999 02 01 2000 12 18

0960-9822 8 19 1998 Sep 24 Multiple functions of the EGF receptor in Drosophila eye development. 1039-48 BACKGROUND: During animal development, cells need to make spatially and temporally regulated fate decisions. These decisions are largely controlled by intercellular signalling, often through receptor tyrosine kinases. One of these, the epidermal growth factor receptor (EGFR), regulates multiple cell fate decisions. Its importance in the recruitment of photoreceptors in the developing fly eye, a useful model for neural development, has already been reported. Other EGFR functions in the eye have not been characterised. RESULTS: We have examined the consequences of removing or activating the EGFR at different stages of eye development. The earliest stages of assembly occurred normally within EGFR- clones--the morphogenetic furrow was unimpeded and the R8 photoreceptor was specified. All subsequent photoreceptor recruitment was blocked. EGFR- clones had a characteristic shape indicating that they had undergone substantial cell death posterior to the furrow, where the differentiation program is normally activated; consistent with this, excess apoptosis was detected. We found that the receptor also regulates cell proliferation in the disc, has an early function at the disc margin (where the morphogenetic furrow initiates) and contributes to the regulation of spacing of the R8 precursors. Finally, we found that activation of the receptor is sufficient to trigger non-R8 photoreceptor development, even in cells in front of the furrow or in the absence of the proneural gene atonal. CONCLUSION: At least five distinct functions of EGFR signalling need to be integrated during fly eye development. These include roles in cell proliferation, survival and differentiation. MRC Laboratory of Molecular Biology, Cambridge, UK. Domínguez M M Wasserman J D JD Freeman M M eng Journal Article Review Review, Tutorial

ENGLAND Curr Biol 9107782 0 DNA-Binding Proteins 0 Eye Proteins 0 Insect Proteins 0 Recombinant Fusion Proteins 0 Ribonucleoproteins 0 ato protein 138391-28-3 ELAV protein EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Cell Differentiation Cell Division Cell Lineage Cell Survival Clone Cells DNA-Binding Proteins physiology Drosophila melanogaster genetics growth & development Eye growth & development Eye Proteins physiology Insect Proteins physiology Larva Morphogenesis Neurons cytology Receptor, Epidermal Growth Factor physiology Recombinant Fusion Proteins physiology Ribonucleoproteins physiology 46 FBrf0155993 22350138 12447392 2002 12 03 2003 01 09

1465-7392 4 12 2002 Dec Planar polarity and actin dynamics in the epidermis of Drosophila. 937-44 Dorsal closure is a morphogenetic process involving the coordinated convergence of two epithelial sheets to enclose the Drosophila melanogaster embryo. Specialized populations of cells at the edges of each epithelial sheet, the dorsal-most epidermal cells, emit actin-based processes that are essential for the proper enclosure of the embryo. Here we show that actin dynamics at the leading edge is preceded by a planar polarization of the dorsal-most epidermal cells associated with a reorganization of the cytoskeleton. An important consequence of this planar polarization is the formation of actin-nucleating centres at the leading edge, which are important in the dynamics of actin. We show that Wingless (Wg) signalling and Jun amino-terminal kinase (JNK) signalling have overlapping but different roles in these events. Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. Kaltschmidt Julia A JA Lawrence Nicola N Morel Véronique V Balayo Tina T Fernández Beatriz García BG Pelissier Anne A Jacinto Antonio A Martinez Arias Alfonso A eng Journal Article

England Nat Cell Biol 100890575 0 Actins 0 Drosophila Proteins 0 Proto-Oncogene Proteins 117758-26-6 wingless protein, Drosophila EC 2.7.1.- JNK-activating protein kinase EC 2.7.1.37 Mitogen-Activated Protein Kinase Kinases IM Actins genetics physiology Animal Cell Polarity genetics physiology Drosophila Proteins genetics physiology Drosophila melanogaster cytology embryology physiology Embryo, Nonmammalian cytology physiology Epidermis cytology physiology Mitogen-Activated Protein Kinase Kinases genetics physiology Morphogenesis genetics Mutation Proto-Oncogene Proteins genetics physiology Signal Transduction genetics physiology Support, Non-U.S. Gov't FBrf0100110 98104252 9441685 1998 02 13 1998 02 13 2000 12 18

0012-1606 192 2 1997 Dec 15 Imaginal tissues of Drosophila melanogaster exhibit different modes of cell proliferation control. 509-22 The highly conserved regulatory mechanisms that control progression of a cell through the cell cycle do not, alone, explain the programmed control of cell proliferation during animal development. Additional controls must coordinate the cell cycle regulators with developmental regulatory events. Here we report studies of cell cycle control in the imaginal tissues of Drosophila melanogaster, specifically in situations where cell cycle progression is regulated by varying the length of the G2 phase. We show that G2-phase arrest in late larval wing imaginal disks requires transcriptional control of stg, a mitotic inducer that encodes a D. melanogaster homologue of the Schizosaccharomyces pombe p80cdc25 phosphatase. In a second study, string transcriptional regulation was also shown to be important for G2-phase regulation in eye disk cells posterior to the morphogenetic furrow. Finally, unlike all other situations described to date, string transcriptional regulation was found not to be the cause of G2 arrest in abdominal histoblasts, these cells being refractory to ectopic expression of stg. This study further establishes string as an important regulator of G2 phase during D. melanogaster development, but also reveals that at least one additional mechanism is utilized to control G2-phase length and thus cell proliferation in different developmental contexts. Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, Sweden. per.kylsten@wgi.su.se Kylsten P P Saint R R eng Journal Article

UNITED STATES Dev Biol 0372762 0 string protein, Drosophila EC 3.1.3.16 Phosphoprotein Phosphatase IM Abdomen growth & development Animal Cell Cycle Cell Division physiology Drosophila melanogaster genetics growth & development radiation effects Eye cytology growth & development G2 Phase Gene Expression Regulation, Developmental Larva Metamorphosis, Biological Mitosis Organ Specificity Phosphoprotein Phosphatase genetics physiology Radiation Tolerance Sense Organs cytology growth & development Support, Non-U.S. Gov't Thorax cytology growth & development Wing cytology growth & development FBrf0064746 94043436 8227123 1993 12 07 1993 12 07 2000 12 18

0021-9525 123 3 1993 Nov Dissociation of the dorsal-cactus complex and phosphorylation of the dorsal protein correlate with the nuclear localization of dorsal. 523-34 The formation of dorsal-ventral polarity in Drosophila requires the asymmetric nuclear localization of the dorsal protein along the D/V axis. This process is regulated by the action of the dorsal group genes and cactus. We show that dorsal and cactus are both phosphoproteins that form a stable cytoplasmic complex, and that the cactus protein is stabilized by its interaction with dorsal. The dorsal-cactus complex dissociates when dorsal is targeted to the nucleus. While the phosphorylation of cactus remains apparently unchanged during early embryogenesis, the phosphorylation state of dorsal correlates with its release from cactus and with its nuclear localization. This differential phosphorylation event is regulated by the dorsal group pathway. Department of Molecular Biology, Princeton University, New Jersey 08544. Whalen A M AM Steward R R eng Journal Article

UNITED STATES J Cell Biol 0375356 0 Antibodies, Monoclonal 0 DNA-Binding Proteins 0 Nuclear Proteins 0 Phosphoproteins 0 dorsal protein, Drosophila 149059-01-8 cactus protein, Drosophila IM Animal Antibodies, Monoclonal Blotting, Western Cell Nucleus metabolism DNA-Binding Proteins isolation & purification metabolism Drosophila melanogaster genetics metabolism Electrophoresis, Polyacrylamide Gel Embryo, Nonmammalian metabolism Nuclear Proteins isolation & purification metabolism Phosphoproteins isolation & purification metabolism Phosphorylation Protein Binding Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0090754 97105850 8948598 1997 01 21 1997 01 21 2002 04 19

0012-1606 180 1 1996 Nov 25 A gradient of cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. 353-64 Dorsoventral polarity in the Drosophila embryo is established by a signaling pathway active on the ventral and ventrolateral surfaces of the embryo. Signal transduction via the protein kinase Pelle frees the Rel-related protein Dorsal from its cytoplasmic inhibitor Cactus, allowing Dorsal to translocate into ventral and ventrolateral nuclei and direct gene expression. Here, we show by immunochemical analyses that Pelle-mediated signaling induces the spatially graded degradation of Cactus. Using a tissue culture system which reconstitutes Pelle-dependent Cactus degradation, we show that a motif in Cactus resembling the sites of signal-dependent phosphorylation in the vertebrate homologs IkappaB-alpha and IkappaB-beta is essential for Pelle-induced Cactus degradation. Substitution of four serines within this motif with nonphosphorylatable alanine residues generated a mutant Cactus that still functions as a Dorsal inhibitor but is resistant to induced degradation. Injection of RNA encoding this altered form of Cactus has a dominant negative effect on establishment of dorsoventral polarity in the embryo. We conclude that dorsoventral signaling results in a Cactus concentration gradient and propose that signal-dependent phosphorylation directs the spatially regulated proteolysis of Cactus protein. Department of Pharmacology, School of Medicine, The University of California at San Diego, La Jolla 92093-0636, USA. Reach M M Galindo R L RL Towb P P Allen J L JL Karin M M Wasserman S A SA eng Journal Article

UNITED STATES Dev Biol 0372762 0 DNA-Binding Proteins 0 Phosphoproteins 0 Recombinant Proteins 149059-01-8 cactus protein, Drosophila EC 2.7.1.- pelle protein EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Amino Acid Sequence Animal Cells, Cultured Comparative Study DNA-Binding Proteins chemistry metabolism Drosophila melanogaster embryology Embryo, Nonmammalian cytology physiology Immunohistochemistry Molecular Sequence Data Phosphoproteins chemistry metabolism Phosphorylation Protein-Serine-Threonine Kinases metabolism Recombinant Proteins metabolism Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0053387 91347366 1908748 1991 09 27 1991 09 27 2003 06 16

0092-8674 66 4 1991 Aug 23 Nanos is the localized posterior determinant in Drosophila. 637-47 Segmental pattern in the Drosophila embryo is established by two maternal factors localized to the anterior and posterior poles of the egg cell. Here we provide molecular evidence that the localized posterior factor is the RNA of the nanos (nos) gene. nos RNA is localized to the posterior pole of early embryos, and nos protein acts at a distance to direct abdomen formation. Synthetic nos RNA has biological activity identical to that of the posterior pole plasm. Injection of nos RNA rescues the segmentation defect of embryos derived from females mutant for all nine known posterior group genes. Injection of nos RNA into the anterior is able to direct formation of ectopic posterior structures. Our results demonstrate that a localized source of nos RNA is sufficient to specify abdominal segmentation and imply that other posterior group genes are required for localization, stabilization, or distribution of the nos gene product. Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Cambridge, Massachusetts. Wang C C Lehmann R R eng GENBANK M60962 M64383 M64384 M72421 M73548 S44812 S44816 S44821 S56137 S56139 Journal Article

UNITED STATES Cell 0413066 0 Insect Hormones 0 RNA, Messenger 142661-95-8 nanos protein, Drosophila IM Cell 1992 Mar 20;68(6):1177 Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Molecular Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Structural Insect Hormones genetics Molecular Sequence Data Morphogenesis RNA, Messenger genetics Restriction Mapping Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0079420 95220663 7705626 1995 05 11 1995 05 11 2002 04 19

0016-6731 139 1 1995 Jan Mutations that alter the timing and pattern of cubitus interruptus gene expression in Drosophila melanogaster. 229-40 The cubitus interruptus (ci) gene is a member of the Drosophila segment polarity gene family and encodes a protein with a zinc finger domain homologous to the vertebrate Gli genes and the nematode tra-1 gene. Three classes of existing mutations in the ci locus alter the regulation of ci expression and can be used to examine ci function during development. The first class of ci mutations causes interruptions in wing veins four and five due to inappropriate expression of the ci product in the posterior compartment of imaginal discs. The second class of mutations eliminates ci protein early in embryogenesis and causes the deletion of structures that are derived from the region including and adjacent to the engrailed expressing cells. The third class of mutations eliminates ci protein later in embryogenesis and blocks the formation of the ventral naked cuticle. The loss of ci expression at these two different stages in embryonic development correlates with the subsequent elimination of wingless expression. Adults heterozygous for the unique ciCe mutation have deletions between wing veins three and four. A similar wing defect is present in animals mutant for the segment polarity gene fused that encodes a putative serine/threonine kinase. In ciCe/+ and fused mutants, the deletions between wing veins three and four correlate with increased ci protein levels in the anterior compartment. Thus, proper regulation of both the ci mRNA and protein appears to be critical for normal Drosophila development. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500. Slusarski D C DC Motzny C K CK Holmgren R R eng NS-28472 NS NINDS Journal Article

UNITED STATES Genetics 0374636 0 DNA-Binding Proteins 0 Insect Hormones 0 Proto-Oncogene Proteins 0 Transcription Factors 0 cubitus interruptus protein 0 engrail protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 2.7.1.- fused protein, Drosophila EC 2.7.1.37 Protein-Serine-Threonine Kinases IM ci Animal DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Female Gene Expression Regulation Genes, Insect genetics Insect Hormones genetics Larva anatomy & histology Male Models, Genetic Mutation Promoter Regions (Genetics) genetics Protein-Serine-Threonine Kinases genetics Proto-Oncogene Proteins genetics Sequence Deletion Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Time Factors Tissue Distribution Transcription Factors genetics Wing anatomy & histology embryology FBrf0108829 99322666 10394362 1999 07 16 1999 07 16 2003 05 05

1097-2765 3 6 1999 Jun PTP-ER, a novel tyrosine phosphatase, functions downstream of Ras1 to downregulate MAP kinase during Drosophila eye development. 741-50 Activation of ERK/MAPK is a key event downstream of RAS. The duration, extent, and timing of MAPK activity is integral to signal specificity. Consequently, inactivation of MAPK by phosphatases has emerged as a critical element in the precise control of signal output. We have cloned and characterized a novel cytoplasmic protein tyrosine phosphatase, PTP-ER, which is related to mammalian PCPTP1, LC-PTP/HePTP, and STEP tyrosine phosphatases. PTP-ER mutants produce extra R7 cells and enhance activated Ras1 signaling. Ectopic expression of PTP-ER dramatically inhibits RAS1/MAPK signaling. PTP-ER binds to and inactivates Drosophila ERK/MAPK; however, it is unable to dephosphorylate and downregulate Drosophila MAPKSevenmaker. Resistance to PTP-ER activity partially accounts for the Sevenmaker mutant phenotype. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA. Karim F D FD Rubin G M GM eng GENBANK AF146594 Journal Article

UNITED STATES Mol Cell 9802571 EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 3.1.3.- ERK phosphatase EC 3.1.3.48 Protein-Tyrosine-Phosphatase EC 3.6.1.- Proto-Oncogene Protein p21(ras) IM Amino Acid Sequence Animal Ca(2+)-Calmodulin Dependent Protein Kinase antagonists & inhibitors genetics metabolism Cell Differentiation Cloning, Molecular Cytoplasm enzymology metabolism Down-Regulation Drosophila melanogaster cytology enzymology genetics growth & development Enzyme Activation Eye enzymology growth & development metabolism Gene Expression Genes, Insect genetics Molecular Sequence Data Mutation Phenotype Phosphorylation Photoreceptors, Invertebrate cytology Protein-Tyrosine-Phosphatase chemistry genetics metabolism Proto-Oncogene Protein p21(ras) genetics metabolism Signal Transduction Suppression, Genetic FBrf0129924 20390091 10801889 2000 08 31 2000 08 31 2000 12 18

0021-9258 275 30 2000 Jul 28 Histone H2A.Z is widely but nonrandomly distributed in chromosomes of Drosophila melanogaster. 23267-72 Variant histones that differ in amino acid sequence from S-phase histones are widespread in eukaryotes, yet the structural changes they cause to nucleosomes and how those changes affect relevant cellular processes have not been determined. H2A.F/Z is a highly conserved family of H2A variants. H2Av, the H2A.F/Z variant of Drosophila melanogaster, was localized in polytene chromosomes by indirect immunofluorescence and in diploid chromosomes by chromatin immunoprecipitation. H2Av was widely distributed in the genome and not limited to sites of active transcription. H2Av was present in thousands of euchromatic bands and the heterochromatic chromocenter of polytene chromosomes, and the H2Av antibody precipitated both transcribed and nontranscribed genes as well as noncoding euchromatic and heterochromatic sequences. The distribution of H2Av was not uniform. The complex banding pattern of H2Av in polytene chromosomes did not parallel the concentration of DNA, as did the pattern of immunofluorescence using H2A antibodies, and the density of H2Av measured by immunoprecipitation varied between different sequences. Of the sequences assayed, H2Av was least abundant on 1. 688 satellite sequences and most abundant on the hsp70 genes. Finally, transcription caused, to an equivalent extent, both H2Av and H2A to be less tightly associated with DNA. Wadsworth Center, New York State Department of Health and Department of Biomedical Sciences, State University of New York, Albany, New York 12201-2002, USA. Leach T J TJ Mazzeo M M Chotkowski H L HL Madigan J P JP Wotring M G MG Glaser R L RL eng GM53476 GM NIGMS Journal Article

UNITED STATES J Biol Chem 2985121R 0 Histones IM Animal Diploidy Drosophila melanogaster genetics metabolism Fluorescent Antibody Technique Histones metabolism Precipitin Tests S Phase Support, U.S. Gov't, P.H.S. FBrf0079893 95286060 7768442 1995 07 06 1995 07 06 2000 12 18

0016-6731 139 3 1995 Mar Regulatory autonomy and molecular characterization of the Drosophila out at first gene. 1331-46 Our previous work has shown that the expression of the Drosophila decapentaplegic (dpp) gene in imaginal disks is controlled by a 30 kb array of enhancers located 3' of the dpp coding region. Here, we describe the cloning and characterization of out at first (oaf), a gene located near this enhancer region. Transcription of oaf results in three classes of alternatively polyadenylated RNAs whose expression is developmentally regulated. All oaf transcripts contain two adjacent open reading frames separated by a single UGA stop codon. Suppression of the UGA codon during translation, as seen previously in Drosophila, could lead to the production of different proteins from the same RNA. During oogenesis, oaf RNA is expressed in nurse cells of all ages and maternally contributed to the egg. During embryonic development, zygotic transcription of the gene occurs in small clusters of cells in most or all segments at the time of germband extension and subsequently in a segmentally repeated pattern in the developing central nervous system. The gene is also expressed in the embryonic, larval and adult gonads of both sexes. We also characterize an enhancer trap line with its transposon inserted within the oaf gene and use it to generate six recessive oaf mutations. All six cause death near the beginning of the first larval instar, with two characterized lines showing nervous system defects. Last, we discuss our data in light of the observation that the enhancers controlling dpp expression in the imaginal disks have no effect on the relatively nearby oaf gene. Department of Cell and Structural Biology, University of Illinois, Urbana 61801, USA. Bergstrom D E DE Merli C A CA Cygan J A JA Shelby R R Blackman R K RK eng GENBANK L31349 L36089 Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 Insect Hormones 0 RNA, Messenger 0 dpp protein, Drosophila IM dpp oaf Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA Transposable Elements genetics Drosophila melanogaster cytology genetics growth & development Enhancer Elements (Genetics) Exons genetics Female Gene Expression Regulation genetics Genes, Insect Genes, Lethal genetics Insect Hormones genetics Introns genetics Male Molecular Sequence Data Oocytes cytology Open Reading Frames genetics Phenotype Promoter Regions (Genetics) RNA, Messenger genetics metabolism Sequence Analysis, DNA Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription, Genetic genetics FBrf0049539 90183788 2516795 1990 04 24 1990 04 24 2000 12 18

0950-1991 106 1 1989 May l(1)pole hole is required maternally for pattern formation in the terminal regions of the embryo. 145-58 Maternal expression of the l(1)pole hole (l(1)ph) gene product is required for the development of the Drosophila embryo. When maternal l(1)ph+ activity is absent, alterations in the embryonic fate map occur as visualized by the expression of segmentation genes fushitarazu and engrailed. If both maternal and zygotic activity is absent, embryos degenerate around 7 h of development. If only maternal activity is missing, embryos complete embryogenesis and show deletions of both anterior and posterior structures. Anteriorly, structures originating from labral and acron head regions are missing. Posteriorly, abdominal segments A8, 9 and 10, the telson and the proctodeum are missing. Similar pattern deletions are observed in embryos derived from the terminal class of female sterile mutations. Thus, the maternal l(1)ph+ gene product is required for the establishment of cell identities at the anterior and posterior poles of the Drosophila embryo. Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115. Ambrosio L L Mahowald A P AP Perrimon N N eng HD17608 HD NICHD HD23684 HD NICHD T32HD07104-09 HD NICHD Journal Article

ENGLAND Development 8701744 IM Animal Blastoderm physiology Cell Differentiation Drosophila melanogaster anatomy & histology embryology genetics Gastrula physiology Gene Expression Microscopy, Electron, Scanning Mitosis Morphogenesis Mutation Nervous System embryology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zygote physiology FBrf0041542 85012656 6434990 1984 11 14 1984 11 14 2000 12 18

0028-0836 311 5983 1984 Sep 20-26 Isolation of the dorsal locus of Drosophila. 262-5 The establishment of embryonic polarity is a crucial step in pattern formation and morphogenesis. In the fruitfly Drosophila melanogaster, embryonic polarity depends primarily on genes expressed in the female during oogenesis. Mutations in these 'maternal effect' genes can lead to major disruptions in normal pattern formation. Two classes of maternal genes essential for the establishment of polarity in the embryo have been identified. Lesions in one class, the 'bicaudal' genes, disrupt the anterior-posterior axis; lesions in the other class disrupt dorsal-ventral polarity, and in the most extreme cases embryos fail to form any ventral or lateral structures. Genetic studies suggest that the anterior-posterior and dorsal-ventral axes may be independent as the defects observed in mutants from each class seem to be restricted to one axis only. The dorsal (dl) locus is one of the maternal effect genes involved in the establishment of dorsal-ventral polarity. Homozygous dl females produce embryos exhibiting the mutant phenotype--complete lack of dorsal-ventral polarity in the strongest alleles--irrespective of the genotype of the father. Although dl is a maternal effect locus and must be expressed during oogenesis, the gene product, or a substance depending on the normal function of the dl gene, seems to be active early in embryogenesis, as the dl phenotype can be partially rescued by injection of cytoplasm from wild-type cleavage-stage embryos. Here we report the molecular cloning of the dorsal locus and a study of its expression. Steward R R McNally F J FJ Schedl P P eng Journal Article

ENGLAND Nature 0410462 0 Actins 0 RNA, Messenger IM Actins genetics Animal Chromosome Mapping Drosophila melanogaster embryology genetics Female Gene Expression Regulation Genes, Structural Oogenesis Ovary physiology RNA, Messenger genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0090823 97108752 8951073 1997 01 23 1997 01 23 2003 06 16

0950-1991 122 11 1996 Nov Role of Bicaudal-D in patterning the Drosophila egg chamber in mid-oogenesis. 3577-86 The Bicaudal-D (Bic-D) gene is required early in Drosophila oogenesis for the differentiation of an oocyte from one of a cluster of 16 interconnected germarial cells. To analyze the role of Bic-D later in oogenesis, we have constructed Drosophila lines in which Bic-D expression is under the control of the hsp70 promoter. In these flies, Bic-D activity can be induced early in oogenesis, allowing an oocyte to be made. Then, by shifting females to non-inducing conditions, Bic-D levels are depleted for the remainder of oogenesis. Using this system, we find that Bic-D is indeed required in the later stages of oogenesis. In ovaries from mutant females, oocyte growth is reduced, apparently due to defects in nurse-cell-to-oocyte transport. Smaller oocyte size results in the misalignment of follicle cells and the underlying germ line, leading to ventralization of dorsal follicle cells and to defects in centripetal cell migration. In addition, we show that Bic-D is required for the localization of specific mRNAs at both the anterior and posterior of the oocyte. Department of Biology, McGill University, Montreal, Canada. Swan A A Suter B B eng Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 Proteins 0 RNA, Messenger 0 gurken protein, Drosophila 0 oskar protein, Drosophila 0 sycaudalD protein, Drosophila 76057-06-2 Transforming Growth Factors IM Animal Animals, Genetically Modified Chorion ultrastructure Drosophila melanogaster genetics Female Gene Expression Regulation, Developmental In Situ Hybridization Insect Hormones genetics physiology Oocytes cytology Oogenesis Ovary cytology Proteins genetics RNA, Messenger metabolism Support, Non-U.S. Gov't Transforming Growth Factors genetics FBrf0108523 99244705 10226011 1999 07 07 1999 07 07 2003 06 16

0950-1991 126 11 1999 Jun Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients. 2527-38 The entire functional even-skipped locus of Drosophila melanogaster is contained within a 16 kilobase region. As a transgene, this region is capable of rescuing even-skipped mutant flies to fertile adulthood. Detailed analysis of the 7.7 kb of regulatory DNA 3' of the transcription unit revealed ten novel, independently regulated patterns. Most of these patterns are driven by non-overlapping regulatory elements, including ones for syncytial blastoderm stage stripes 1 and 5, while a single element specifies both stripes 4 and 6. Expression analysis in gap gene mutants showed that stripe 5 is restricted anteriorly by Krüppel and posteriorly by giant, the same repressors that regulate stripe 2. Consistent with the coregulation of stripes 4 and 6 by a single cis-element, both the anterior border of stripe 4 and the posterior border of stripe 6 are set by zygotic hunchback, and the region between the two stripes is 'carved out' by knirps. Thus the boundaries of stripes 4 and 6 are set through negative regulation by the same gap gene domains that regulate stripes 3 and 7 (Small, S., Blair, A. and Levine, M. (1996) Dev. Biol. 175, 314-24), but at different concentrations. The 3' region also contains a single element for neurogenic expression in ganglion mother cells 4-2a and 1-1a, and neurons derived from them (RP2, a/pCC), suggesting common regulators in these lineages. In contrast, separable elements were found for expression in EL neurons, U/CQ neurons and the mesoderm. The even-skipped 3' untranslated region is required to maintain late stage protein expression in RP2 and a/pCC neurons, and appears to affect protein levels rather than mRNA levels. Additionally, a strong pairing-sensitive repression element was localized to the 3' end of the locus, but was not found to contribute to efficient functional rescue. Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA. Fujioka M M Emi-Sarker Y Y Yusibova G L GL Goto T T Jaynes J B JB eng Journal Article

ENGLAND Development 8701744 0 3' Untranslated Regions 0 DNA-Binding Proteins 0 ESPD protein, E coli 0 Homeodomain Proteins 0 KNI protein 0 Kruppel protein 0 Repressor Proteins 0 Transcription Factors 0 giant protein 108911-13-3 even-skipped protein, Drosophila IM 3' Untranslated Regions genetics Animal Blastoderm metabolism Body Patterning genetics DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Gene Expression Regulation, Developmental genetics Homeodomain Proteins genetics Mesoderm metabolism Nervous System embryology Phenotype Repressor Proteins genetics Support, U.S. Gov't, Non-P.H.S. Transcription Factors genetics Transgenes genetics FBrf0039452 84029843 6414883 1983 12 20 1983 12 20 2000 12 18

0016-6731 105 2 1983 Oct A cytogenetic analysis of the chromosomal region surrounding the alpha-glycerophosphate dehydrogenase locus of Drosophila melanogaster. 371-86 The chromosomal region surrounding the structural gene for alpha-glycerophosphate dehydrogenase (alpha Gpdh, 2-20.5) of Drosophila melanogaster has been studied in detail. Forty-three EMS-induced recessive lethal mutations and five previously identified visible mutations have been localized within the 25A-27D region of chromosome 2 by deficiency mapping and in some cases by a recombination analysis. The 43 lethal mutations specify 17 lethal loci. alpha Gpdh has been localized to a single polytene chromosome band, 25F5, and there apparently are no lethals that map to the alpha Gpdh locus. Kotarski M A MA Pickert S S MacIntyre R J RJ eng AG01811 AG NIA GM07617 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 1.1.- Glycerolphosphate Dehydrogenase IM Animal Chromosome Mapping Comparative Study Drosophila melanogaster genetics Genes, Lethal Genes, Recessive Genes, Structural Glycerolphosphate Dehydrogenase genetics Mutation Support, U.S. Gov't, P.H.S. FBrf0141645 21612227 11744370 2001 12 17 2002 05 10

0925-4773 110 1-2 2002 Jan A P-insertion screen identifying novel X-linked essential genes in Drosophila. 71-83 The recent determination and annotation of the entire euchromatic sequence of the Drosophila melanogaster genome predicted the existence of about 13600 different genes (Science 287 (2000) 2185; http://www.fruitfly.org/annot/index.html). In parallel, the Berkeley Drosophila Genome Project (BDGP) has undertaken systematic P-insertion screens, to isolate new lethals and misexpressing lines. To date, however, the genes of the X chromosome have been under-represented in the screens performed. In order both to characterize several X-linked genes of prime interest to our laboratories and contribute to the collection of lethal P-insertions available to the community, we performed a P-insertion mutagenesis of the X chromosome. Using the PlacW and PGawB P-elements as mutagens, we generated two complementary sets of enhancer-trap lines, l(1)(T)PL and l(1)(T)PG, respectively, which both contain a reporter gene whose developmental expression can be monitored when driven by nearby enhancer sequences. We report here the characterization of 260 new insertions, mapping to 133 different genes or predicted CGs. Of these, 83 correspond to genes for which no lethal mutation had yet been reported. For 64 of those, we could confirm that lethality was solely due to the P-element insertion. The primary molecular data, reporter gene expression patterns (observed in embryos, third instar larvae and adult ovaries) and proposed CG assignment for each strain can be accessed and updated on our website at the following address: http://www-cbd.ups-tlse.fr:8080/screen. Centre de Biologie du Développement, UMR 5547 CNRS/UPS, 118 Route de Narbonne, 31062 Toulouse Cedex, France. Bourbon Henri-Marc HM Gonzy-Treboul Geneviève G Peronnet Frédérique F Alin Marie-Francoise MF Ardourel Claude C Benassayag Corinne C Cribbs David D Deutsch Jean J Ferrer Pierre P Haenlin Marc M Lepesant Jean-Antoine JA Noselli Stéphane S Vincent Alain A eng Journal Article

Ireland Mech Dev 9101218 IM Animal Animals, Genetically Modified Crosses, Genetic Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Female Gene Expression Regulation, Developmental Genes, Insect Genes, Lethal Genes, Reporter Lac Operon Linkage (Genetics) Male Mutagenesis, Insertional Support, Non-U.S. Gov't X Chromosome genetics FBrf0051592 91209246 2128477 1991 05 28 1991 05 28 2000 12 18

0950-1991 110 3 1990 Nov The pattern of transcription of the neurogenic gene Delta of Drosophila melanogaster. 905-14 The function of the Delta locus of Drosophila melanogaster is required for the correct separation of neural and epidermal cell lineages. We describe here the transcriptional organization of this locus and the spatial pattern of mRNA accumulation during embryogenesis. Delta produces three mRNAs with protein-coding capacity, which differ only at their untranslated 3' ends and thus encode the same protein; other minor RNAs from the locus are shown not to have any protein-coding capacity and to correspond to introns. No indications were obtained for multiple translational products of the locus. In situ hybridization using digoxigenin-labelled probes confirms that Delta RNA is present at high concentration in all presumptive neurogenic territories of the embryo. Since all the constituent cells of these territories contain Delta RNA, a differential distribution of the protein among the derivatives of the neuroectodermal cells is improbable. Some time after segregation of lineages, Delta RNA reappears in neuroblasts. The possible significance of these observations with respect to the function of the Delta product during lineage segregation is discussed. Institut für Entwicklungsphysiologie, Universität zu Köln, Federal Republic of Germany. Haenlin M M Kramatschek B B Campos-Ortega J A JA eng Journal Article

ENGLAND Development 8701744 0 RNA, Messenger IM Delta Animal Drosophila melanogaster genetics Genes physiology Nervous System embryology RNA, Messenger analysis Support, Non-U.S. Gov't Transcription, Genetic genetics FBrf0068701 94125277 8295076 1994 03 03 1994 03 03 2000 12 18

0167-7063 9 1 1993 Aug Analysis of the antennal phenotype in the Drosophila mutant lozenge. 29-53 Previous work on the lozenge (lz) gene complex of D. melanogaster has focused on the compound eye. Here we study the effects of 22 lz mutations on the antennal sensilla. The antenna of strong lz alleles is characterized by a lack of basiconic sensilla and by a significantly increased density of coeloconic sensilla. Intermediate alleles have few basiconic sensilla, they exhibit a highly increased density of trichoid sensilla, but a normal coeloconic density. Basiconic sensilla on the maxillary palps are weakly affected even by strong lz alleles. The antennal phenotype for most of the strong and intermediate mutants is partially dominant over wild type. Although this complicates the interpretation of complementation data, 12 selected mutants that were studied in heteroallelic combinations seem to define a single cistron. Temperature shifts of the lztsl allele showed that gene activity is crucial from about 87% of the third larval instar up to 7% of pupal life. Applying restrictive temperature early during this period results in a 'novel' phenotype that is characterized by a dramatic decrease in the density of trichoid sensilla, whereas a late pulse of restrictive temperature leads to a 'normal' intermediate phenotype. Our data suggest that the lz gene controls at least five different functions in the antenna: the size of the third antennal segment, the overall number and density of sensilla, the proportions of the 3 types of sensilla, and the generation of basiconic sensilla. Institute of Zoology, University of Fribourg, Switzerland. Stocker R F RF Gendre N N Batterham P P eng Journal Article

ENGLAND J Neurogenet 8406473 IM lz Alleles Animal Drosophila melanogaster genetics Genetic Complementation Test Mutation Phenotype Sense Organs physiology Support, Non-U.S. Gov't Temperature FBrf0102958 98315100 9649526 1998 08 24 1998 08 24 2000 12 18

0016-6731 149 3 1998 Jul The Y chromosomal fertility factor Threads in Drosophila hydei harbors a functional gene encoding an axonemal dynein beta heavy chain protein. 1363-76 To understand the contradiction between megabase-sized lampbrush loops and putative protein encoding genes both associated with the loci of Y chromosomal fertility genes of Drosophila on the molecular level, we used PCR-mediated cloning to identify and isolate the cDNA sequence of the Y chromosomal Drosophila hydei gene DhDhc7(Y). Alignment of the sequences of the putative protein DhDhc7(Y) and the outer arm dynein beta heavy chain protein DYH2 of Tripneustes gratilla shows homology over the entire length of the protein chains. Therefore the proteins can be assumed to fulfill orthologous functions within the sperm tail axonemes of both species. Functional dynein beta heavy chain molecules, however, are necessary for the assembly and attachment of outer dynein arms within the sperm tail axoneme. Localization of DhDhc7(Y) to the fertility factor Threads, comprising at least 5.1 Mb of transcriptionally active repetitive DNA, results from an infertile Threads- mutant where large clusters of Threads specifically transcribed satellites and parts of DhDhc7(Y) encoding sequences are missing simultaneously. Consequently, the complete lack of the outer dynein arms in Threads- males most probably causes sperm immotility and hence infertility of the fly. Moreover, preliminary sequence analysis and several other features support the hypothesis that DhDhc7(Y) on the lampbrush loops Threads in D. hydei and Dhc-Yh3 on the lampbrush loops kl-5 in Drosophila melanogaster on the heterochromatic Y chromosome of both species might indeed code for orthologous dynein beta heavy chain proteins. Dipartimento di Genetica e Biologia Molecolare, Universita di Roma 'La Sapienza,' I-00185 Roma, Italia. Kurek R R Reugels A M AM Glätzer K H KH Bünemann H H eng GENBANK AF031494 Journal Article

UNITED STATES Genetics 0374636 0 DNA Primers 0 Macromolecular Systems EC 3.6.1.33 Dynein ATPase IM Amino Acid Sequence Animal Base Sequence Chromosome Mapping Cloning, Organism Crosses, Genetic DNA Primers Drosophila genetics metabolism Drosophila melanogaster genetics Dynein ATPase biosynthesis chemistry genetics Female Fertility genetics Genes, Insect Macromolecular Systems Male Molecular Sequence Data Polymerase Chain Reaction Support, Non-U.S. Gov't Testis ultrastructure Y Chromosome FBrf0108951 99307069 10375496 1999 08 19 1999 08 19 2003 07 30

0950-1991 126 14 1999 Jun The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. 3035-46 Cell migrations are found throughout the animal kingdom and are among the most dramatic and complex of cellular behaviors. Historically, the mechanics of cell migration have been studied primarily in vitro, where cells can be readily viewed and manipulated. However, genetic approaches in relatively simple model organisms are yielding additional insights into the molecular mechanisms underlying cell movements and their regulation during development. This review will focus on these simple model systems where we understand some of the signaling and receptor molecules that stimulate and guide cell movements. The chemotactic guidance factor encoded by the Caenorhabditis elegans unc-6 locus, whose mammalian homolog is Netrin, is perhaps the best known of the cell migration guidance factors. In addition, receptor tyrosine kinases (RTKs), and FGF receptors in particular, have emerged as key mediators of cell migration in vivo, confirming the importance of molecules that were initially identified and studied in cell culture. Somewhat surprisingly, screens for mutations that affect primordial germ cell migration in Drosophila have revealed that enzymes involved in lipid metabolism play a role in guiding cell migration in vivo, possibly by producing and/or degrading lipid chemoattractants or chemorepellents. Cell adhesion molecules, such as integrins, have been extensively characterized with respect to their contribution to cell migration in vitro and genetic evidence now supports a role for these receptors in certain instances in vivo as well. The role for non-muscle myosin in cell motility was controversial, but has now been demonstrated genetically, at least in some cell types. Currently the best characterized link between membrane receptor signaling and regulation of the actin cytoskeleton is that provided by the Rho family of small GTPases. Members of this family are clearly essential for the migrations of some cells; however, key questions remain concerning how chemoattractant and chemorepellent signals are integrated within the cell and transduced to the cytoskeleton to produce directed cell migration. New types of genetic screens promise to fill in some of these gaps in the near future. Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA. dmontell@jhmi.edu Montell D J DJ eng Journal Article Review Review, Tutorial

ENGLAND Development 8701744 0 Cell Adhesion Molecules 0 Helminth Proteins 0 Lipids 0 Receptors, Cell Surface 0 Receptors, Fibroblast Growth Factor 0 Transcription Factors 0 UNC-6 protein, C elegans 0 VAB-8 protein, C elegans 0 netrin receptors EC 3.6.1.- GTP Phosphohydrolases EC 3.6.1.4 Myosins IM Animal Axons metabolism Caenorhabditis elegans embryology genetics growth & development Cell Adhesion Molecules metabolism Cell Movement genetics Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian cytology GTP Phosphohydrolases metabolism Helminth Proteins genetics metabolism Lipids metabolism Myosins metabolism Receptors, Cell Surface genetics metabolism Receptors, Fibroblast Growth Factor metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors metabolism 92 FBrf0155713 22378565 12490551 2002 12 19 2003 03 14 2003 06 16

0950-1991 130 3 2003 Feb Functional subdivision of trunk visceral mesoderm parasegments in Drosophila is required for gut and trachea development. 439-49 In Drosophila, trunk visceral mesoderm, a derivative of dorsal mesoderm, gives rise to circular visceral muscles. It has been demonstrated that the trunk visceral mesoderm parasegment is subdivided into at least two domains by connectin expression, which is regulated by Hedgehog and Wingless emanating from the ectoderm. We now extend these findings by examining a greater number of visceral mesodermal genes, including hedgehog and branchless. Each visceral mesodermal parasegment appears to be divided into five or six regions, based on differences in expression patterns of these genes. Ectodermal Hedgehog and Wingless differentially regulate the expression of these metameric targets in trunk visceral mesoderm. hedgehog expression in trunk visceral mesoderm is responsible for maintaining its own expression and con expression. hedgehog expressed in visceral mesoderm parasegment 3 may also be required for normal decapentaplegic expression in this region and normal gastric caecum development. branchless expressed in each trunk visceral mesodermal parasegment serves as a guide for the initial budding of tracheal visceral branches. The metameric pattern of trunk visceral mesoderm, organized in response to ectodermal instructive signals, is thus maintained at a later time via autoregulation, is required for midgut morphogenesis and exerts feedback effect on trachea, ectodermal derivatives. Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Hosono Chie C Takaira Katsumi K Matsuda Ryo R Saigo Kaoru K eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Insect Proteins 0 Muscle Proteins 0 Proto-Oncogene Proteins 0 branchless protein, Drosophila 0 connectin 0 dpp protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.37 Protein Kinases IM Animal Animals, Genetically Modified Body Patterning genetics Digestive System embryology Drosophila Proteins genetics Drosophila melanogaster embryology genetics Feedback Gene Expression Regulation, Developmental Genes, Insect In Situ Hybridization Insect Proteins genetics Mesoderm cytology Models, Biological Muscle Proteins genetics Protein Kinases genetics Proto-Oncogene Proteins genetics Signal Transduction Support, Non-U.S. Gov't Trachea embryology FBrf0056125 93093465 1459454 1993 01 13 1993 01 13 2000 12 18

0890-9369 6 12A 1992 Dec Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development. 2299-311 Recently, we reported the cloning of the Drosophila melanogaster homolog of the vertebrate CCAAT/enhancer-binding protein (C/EBP). Here, we describe studies of the DNA-binding and dimerization properties of Drosophila C/EBP (DmC/EBP), as well as its tissue distribution, developmental regulation, and essential role in embryonic development and conclude that it bears functional as well as structural similarity to mammalian C/EBP. DmC/EBP contains a basic region/leucine zipper (bZIP) DNA-binding domain very similar to that of mammalian C/EBP and the purified C/EBPs bound to DNA with the same sequence specificity. Among the DNA sequences that DmC/EBP bound with high affinity was a conserved site within the promoter of the DmC/EBP gene itself. In vitro, DmC/EBP and mammalian C/EBP specifically formed functional heterodimers; however, as we found no evidence for a family of DmC/EBPs, DmC/EBP may function as a homodimer in vivo. The DmC/EBP protein was expressed predominantly during late embryogenesis in the nuclei of a restricted set of differentiating cell types, such as the lining of the gut and epidermis, similar to the mammalian tissues that express C/EBP. We have characterized mutations in the DmC/EBP gene and found that deleting the gene caused late embryonic lethality. Embryos that lack C/EBP die just before or just upon hatching. The lethal phenotype of C/EBP mutants can be rescued with the cloned C/EBP gene introduced by P-element-mediated germ-line transformation. The strict requirement for C/EBP during Drosophila embryogenesis, coupled with its structural and functional similarities to mammalian C/EBP, provides a useful genetic system in which to study the role of C/EBP in development. Howard Hughes Research Laboratory, Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210. Rørth P P Montell D J DJ eng R29GM46425 GM NIGMS Journal Article

UNITED STATES Genes Dev 8711660 0 CCAAT-Enhancer-Binding Proteins 0 DNA-Binding Proteins 0 Nuclear Proteins 0 Transcription Factors 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Blotting, Northern CCAAT-Enhancer-Binding Proteins Cloning, Molecular DNA metabolism DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics Escherichia coli Germ Cells Molecular Sequence Data Nuclear Proteins genetics metabolism Organ Specificity genetics Promoter Regions (Genetics) Protein Binding Restriction Mapping Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism Transformation, Genetic FBrf0088550 96217926 8675012 1996 08 12 1996 08 12 2002 12 26

0890-9369 10 10 1996 May 15 Promoter specificity mediates the independent regulation of neighboring genes. 1260-70 Although enhancers can exert their influence over great distances, their effect is generally limited to a single gene. To discern the mechanism by which this constraint can he mediated, we have studied three neighboring Drosophila genes: decapentaplegic (dpp), SLY1 homologous (Slh) and out at first (oaf). Several dpp enhancers are positioned close to Slh and oaf, and yet these genes are unaffected by the dpp elements. However, when a transposon is located within the oaf gene, the dpp enhancers activate the more distant transposon promoters while still ignoring the closer Slh and oaf start sites. To test whether this promoter specificity accounts for the regulatory autonomy normally found for the three genes, we used in vivo gene targeting to replace the oaf promoter with a dpp-compatible one in an otherwise normal chromosome. Strikingly, this chimeric gene is now activated by the dpp enhancers. Thus, the properties of the promoters themselves are sufficient to mediate the autonomous regulation of genes in this region. Department of Cell and Structural Biology, University of Illinois, Urbana 61801, USA. Merli C C Bergstrom D E DE Cygan J A JA Blackman R K RK eng GENBANK U63852 U95037 Journal Article

UNITED STATES Genes Dev 8711660 0 Carrier Proteins 0 Fungal Proteins 0 Insect Hormones 0 Sly1 protein, S cerevisiae 0 dpp protein, Drosophila 9007-49-2 DNA IM Animal Base Sequence Carrier Proteins genetics DNA Drosophila genetics Drosophila melanogaster genetics Enhancer Elements (Genetics) Fungal Proteins genetics Gene Expression Regulation Genes, Insect Insect Hormones genetics Molecular Sequence Data Promoter Regions (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0101895 98191580 9530502 1998 05 04 1998 05 04 2000 12 18

0147-006X 21 1998 Gene discovery in Drosophila: new insights for learning and memory. 407-44 Genetic approaches have been used to investigate increasingly complex biological systems. Here we review the current state of genetic analysis of learning and memory in the fruitfly, Drosophila melanogaster. Emerging findings support two main themes. First, discovery and manipulation of genes involved with behavioral plasticity in genetically accessible systems such as D. melanogaster enables dissection of the biochemical, cellular, anatomical, and behavioral pathways of learning and memory. Second, because core cellular mechanisms of simple forms of learning are evolutionarily conserved, biological pathways discovered in invertebrates are likely to be conserved in vertebrate systems as well. Cold Spring Harbor Laboratory, New York 11724, USA. Dubnau J J Tully T T eng Journal Article Review Review, Tutorial

UNITED STATES Annu Rev Neurosci 7804039 IM Animal Drosophila melanogaster genetics Genes, Insect physiology Learning physiology Memory physiology 168 FBrf0052828 90175362 1968635 1990 04 06 1990 04 06 2000 12 18

0027-8424 87 5 1990 Mar "Site-selected" transposon mutagenesis of Drosophila. 1686-90 Despite the wide range of techniques that can be brought to bear on the study of basic processes in Drosophila, there are still deficiencies in our armory. One of these is an ability to select mutants in cases where the gene is known and has been cloned, but where we are ignorant of the associated phenotype. We describe here a solution to this problem as applied to a model system, the singed (sn) locus. Our method is a combination of classical genetics and molecular biology: sib selection plus the polymerase chain reaction. We have used the method to isolate rare individuals with P-element-induced alleles of sn merely by recognition of the DNA structures induced at the locus by transposon insertion. Phenotypic criteria were used only retrospectively to verify our diagnoses. There are obvious implications of this technique for the mutagenesis of other organisms. Department of Genetics, University of Glasgow, Scotland. Kaiser K K Goodwin S F SF eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA Transposable Elements 0 Oligonucleotide Probes IM Animal Base Sequence Crosses, Genetic DNA Transposable Elements Drosophila melanogaster genetics Female Male Molecular Sequence Data Mutation Oligonucleotide Probes Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Support, Non-U.S. Gov't FBrf0131354 20517449 11062264 2000 11 21 2000 12 07

0021-9525 151 3 2000 Oct 30 D-Titin: a giant protein with dual roles in chromosomes and muscles. 639-52 Previously, we reported that chromosomes contain a giant filamentous protein, which we identified as titin, a component of muscle sarcomeres. Here, we report the sequence of the entire titin gene in Drosophila melanogaster, D-Titin, and show that it encodes a two-megadalton protein with significant colinear homology to the NH(2)-terminal half of vertebrate titin. Mutations in D-Titin cause chromosome undercondensation, chromosome breakage, loss of diploidy, and premature sister chromatid separation. Additionally, D-Titin mutants have defects in myoblast fusion and muscle organization. The phenotypes of the D-Titin mutants suggest parallel roles for titin in both muscle and chromosome structure and elasticity, and provide new insight into chromosome structure. Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA. Machado C C Andrew D J DJ eng Journal Article

UNITED STATES J Cell Biol 0375356 0 Chromosomal Proteins, Non-Histone 0 Insect Proteins 0 Muscle Proteins 0 connectin 0 kettin EC 2.7.1.37 Protein Kinases IM Animal Cell Fusion Chromatids chemistry genetics metabolism Chromosomal Proteins, Non-Histone chemistry genetics metabolism Chromosome Breakage genetics Chromosome Segregation Chromosomes chemistry genetics metabolism Drosophila melanogaster cytology embryology genetics metabolism Embryo, Nonmammalian embryology metabolism Insect Proteins chemistry genetics metabolism Mitosis genetics Molecular Weight Muscle Proteins chemistry genetics metabolism Muscles chemistry cytology embryology metabolism Mutation genetics Phenotype Protein Kinases chemistry genetics metabolism Sarcomeres chemistry metabolism Support, Non-U.S. Gov't FBrf0099022 98033257 9367434 1997 12 11 1997 12 11 2000 12 18

0950-1991 124 19 1997 Oct Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos. 3787-96 The midline glia of the Drosophila embryonic nerve cord undergo a reduction in cell number after facilitating commissural tract morphogenesis. The numbers of midline glia entering apoptosis at this stage can be increased by a loss or reduction of function in genes of the spitz group or Drosophila EGF receptor (DER) pathway. Argos, a secreted molecule with an atypical EGF motif, is postulated to function as a DER antagonist. In this work, we assess the role of argos in the determination of midline glia cell number. Although all midline glia express DER, argos expression is restricted to the midline glia which do not enter apoptosis. Fewer midline glia enter apoptosis in embryos lacking argos function. Ectopic expression of argos is sufficient to remove all DER-expressing midline glia from the nerve cord, even those that already express argos. DER expression is not terminated in the midline glia after spitz group signaling triggers changes in gene expression. It is therefore likely that an attenuation of DER signaling by Argos is integrated with the augmentation of DER signaling by Spitz throughout the period of reduction of midline glia number. We suggest that signaling by Spitz but not Argos is restricted to adhesive junctions. In this manner, midline glia not forming signaling junctions remain sensitive to juxtacrine Argos signaling, while an autocrine Argos signal is excluded by the adhesive junction. Department of Biology, McMaster University, Hamilton ON, Canada. Stemerdink C C Jacobs J R JR eng Journal Article

ENGLAND Development 8701744 0 Eye Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 RNA, Messenger 0 Receptors, Invertebrate Peptide 0 epidermal growth factor receptor homolog, Drosophila 147954-53-8 gil protein 148175-53-5 spitz protein 62229-50-9 Epidermal Growth Factor EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Axons physiology ultrastructure Body Patterning Drosophila melanogaster embryology genetics Embryo, Nonmammalian cytology physiology Epidermal Growth Factor biosynthesis Eye Proteins biosynthesis physiology Gene Expression Regulation, Developmental Genes, Insect Heat Membrane Proteins biosynthesis physiology Models, Biological Nerve Tissue Proteins biosynthesis physiology Nervous System embryology Neuroglia cytology physiology RNA, Messenger biosynthesis Receptor, Epidermal Growth Factor biosynthesis physiology Receptors, Invertebrate Peptide biosynthesis physiology Signal Transduction Support, Non-U.S. Gov't Transcription, Genetic FBrf0058140 93223681 8096812 1993 05 13 1993 05 13 2002 11 08

0261-4189 12 4 1993 Apr Silencers in abdominal-B, a homeotic Drosophila gene. 1415-25 Homeotic genes determine the developmental fates of cells. Restriction of their expression along the body axis is of prime importance for normal development. We searched for cis-regulatory sequences within Abdominal-B (Abd-B), a homeotic Drosophila gene, by testing genomic Abd-B fragments for their ability to confer beta-galactosidase (beta-gal) expression in transformed embryos. One of the Abd-B fragments, called IAB5, mediates a beta-gal pattern restricted along the body axis to the Abd-B expression domain. Alterations of the IAB5 pattern in gap mutants provide evidence that the protein products of the gap genes hunchback, Krüppel and knirps act as repressors through IAB5. The anterior Abd-B expression limit is apparently determined by Krüppel repression, whereas the knirps repressor may be responsible for the graded Abd-B expression within the Abd-B domain. IAB5 and two other fragments called MCP and FAB show region-specific silencing activity: they suppress at a distance beta-gal expression mediated by a linked heterologous enhancer. Silencing requires hunchback as well as Polycomb function and evidently provides maintenance of Abd-B expression limits throughout embryogenesis. We conclude that transcriptional repression is a key mechanism operating at multiple levels to control Abd-B expression. The striking similarities between the control of Abd-B and of Ultrabithorax, another homeotic Drosophila gene, may point to a universal principle underlying homeotic gene regulation. Zoological Institute, University of Zürich, Switzerland. Busturia A A Bienz M M eng Journal Article

ENGLAND EMBO J 8208664 0 Abd-B proteins, Drosophila 0 Insect Hormones 0 RNA, Messenger 0 Repressor Proteins IM Abd-B Animal Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Homeobox Insect Hormones genetics Morphogenesis Promoter Regions (Genetics) RNA, Messenger genetics Regulatory Sequences, Nucleic Acid Repressor Proteins physiology Support, Non-U.S. Gov't Transcription, Genetic FBrf0101997 98186267 9504923 1998 05 14 1998 05 14 2000 12 18

0016-6731 148 2 1998 Feb hold up is required for establishment of oocyte positioning, follicle cell fate and egg polarity and cooperates with Egfr during Drosophila oogenesis. 767-73 In Drosophila the posterior positioning of the oocyte within the germline cluster defines the initial asymmetry during oogenesis. From this early event, specification of both body axes is controlled through reciprocal signaling between germline and soma. Here it is shown that the mutation hold up (hup) affects oocyte positioning in the egg chamber, follicle cell fate and localization of different markers in the growing oocytes. This occurs not only in dicephalic egg chambers, but also in oocytes normally located at the posterior. Generation of mosaic egg chambers indicates that hup has to be at least somatically required. Possible interactions of hup with Egfr, the Drosophila epidermal growth factor receptor homolog, have been investigated in homozygous double mutants constructed by recombination. Stronger new ovarian phenotypes have been obtained, the most striking being accumulation of follicle cells in multiple layers posteriorly to the oocyte. It is proposed that the hup gene product is a component of the molecular machinery that leads to the establishment of polarity both in follicle cell layer and oocyte, acting in the same or in a parallel pathway of Egfr. Istituto Internazionale di Genetica e Biofisica, Napoli, Italy. Rotoli D D Andone S S Tortiglione C C Manzi A A Malva C C Graziani F F eng Journal Article

UNITED STATES Genetics 0374636 0 Indoles 0 RNA, Messenger 47165-04-8 DAPI EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Drosophila melanogaster cytology physiology Genes, Insect genetics Histocytochemistry In Situ Hybridization Indoles metabolism Morphogenesis genetics physiology Mutation genetics Oocytes cytology physiology Oogenesis physiology RNA, Messenger metabolism Receptor, Epidermal Growth Factor metabolism Support, Non-U.S. Gov't FBrf0151271 22131263 12135920 2002 07 23 2002 09 11

0950-1991 129 16 2002 Aug Dpp signalling is a key effector of the wing-body wall subdivision of the Drosophila mesothorax. 3815-23 During development, the imaginal wing disc of Drosophila is subdivided along the proximal-distal axis into different territories that will give rise to body wall (notum and mesothoracic pleura) and appendage (wing hinge and wing blade). Expression of the Iroquois complex (Iro-C) homeobox genes in the most proximal part of the disc defines the notum, since Iro-C(-) cells within this territory acquire the identity of the adjacent distal region, the wing hinge. Here we analyze how the expression of Iro-C is confined to the notum territory. Neither Wingless signalling, which is essential for wing development, nor Vein-dependent EGFR signalling, which is needed to activate Iro-C, appear to delimit Iro-C expression. We show that a main effector of this confinement is the TGFbeta homolog Decapentaplegic (Dpp), a molecule known to pattern the disc along its anterior-posterior axis. At early second larval instar, the Dpp signalling pathway functions only in the wing and hinge territories, represses Iro-C and confines its expression to the notum territory. Later, Dpp becomes expressed in the most proximal part of the notum and turns off Iro-C in this region. This downregulation is associated with the subdivision of the notum into medial and lateral regions. Centro de Biología Molecular Severo Ochoa, CSIC and UAM, Cantoblanco, 28049 Madrid, Spain. Cavodeassi Florencia F Rodríguez Isabel I Modolell Juan J eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Proto-Oncogene Proteins 0 dpp protein, Drosophila 117758-26-6 wingless protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Body Patterning Drosophila Proteins genetics physiology Drosophila melanogaster genetics growth & development physiology Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Proto-Oncogene Proteins genetics physiology Receptor, Epidermal Growth Factor genetics physiology Signal Transduction Support, Non-U.S. Gov't Wing growth & development FBrf0131405 20519456 11063697 2000 11 21 2001 01 04

0016-6731 156 3 2000 Nov A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila. 1231-42 kinase suppressor of Ras (ksr) encodes a putative protein kinase that by genetic criteria appears to function downstream of RAS in multiple receptor tyrosine kinase (RTK) pathways. While biochemical evidence suggests that the role of KSR is closely linked to the signal transduction mechanism of the MAPK cascade, the precise molecular function of KSR remains unresolved. To further elucidate the role of KSR and to identify proteins that may be required for KSR function, we conducted a dominant modifier screen in Drosophila based on a KSR-dependent phenotype. Overexpression of the KSR kinase domain in a subset of cells during Drosophila eye development blocks photoreceptor cell differentiation and results in the external roughening of the adult eye. Therefore, mutations in genes functioning with KSR might modify the KSR-dependent phenotype. We screened approximately 185,000 mutagenized progeny for dominant modifiers of the KSR-dependent rough eye phenotype. A total of 15 complementation groups of Enhancers and four complementation groups of Suppressors were derived. Ten of these complementation groups correspond to mutations in known components of the Ras1 pathway, demonstrating the ability of the screen to specifically identify loci critical for Ras1 signaling and further confirming a role for KSR in Ras1 signaling. In addition, we have identified 4 additional complementation groups. One of them corresponds to the kismet locus, which encodes a putative chromatin remodeling factor. The relevance of these loci with respect to the function of KSR and the Ras1 pathway in general is discussed. Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA. Therrien M M Morrison D K DK Wong A M AM Rubin G M GM eng Journal Article

UNITED STATES Genetics 0374636 62-50-0 Ethyl Methanesulfonate EC 2.7.1.- KSR-1 protein kinase EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.37 Protein Kinases IM Amino Acid Sequence Animal Chromosome Mapping Crosses, Genetic Drosophila melanogaster anatomy & histology enzymology genetics Ethyl Methanesulfonate Eye anatomy & histology ultrastructure Female Genes, Dominant Genes, Insect Genetic Complementation Test Male Microscopy, Electron, Scanning Molecular Sequence Data Mutagenesis Phenotype Protein Kinases genetics Receptor Protein-Tyrosine Kinases genetics Recombination, Genetic Sequence Alignment Sequence Homology, Amino Acid Signal Transduction physiology Support, Non-U.S. Gov't FBrf0137351 21396584 11504941 2001 08 15 2001 09 20 2002 06 18

0027-8424 98 17 2001 Aug 14 A Drosophila PIAS homologue negatively regulates stat92E. 9563-8 Transcriptional activation by, and therefore the physiologic impact of, activated tyrosine-phosphorylated STATs (signal transducers and activators of transcription) may be negatively regulated by proteins termed PIAS (protein inhibitors of activated stats), as shown by previous experiments with mammalian cells in culture. Here, by using the genetic modifications in Drosophila, we demonstrate the in vivo functional interaction of the Drosophila homologues stat92E and a Drosophila PIAS gene (dpias). To this end we use a LOF allele and conditionally overexpressed dpias in JAK-STAT pathway mutant backgrounds. We conclude that the correct dpias/stat92E ratio is crucial for blood cell and eye development. Laboratories of Molecular Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA. Betz A A Lampen N N Martinek S S Young M W MW Darnell J E JE Jr eng AI32440 AI NIAID AI32489 AI NIAID Journal Article

United States Proc Natl Acad Sci U S A 7505876 0 Carrier Proteins 0 DNA-Binding Proteins 0 Insect Proteins 0 PIAS1 protein 0 Proteins 0 STAT92E protein 0 Trans-Activators 0 Zimp protein EC 2.7.1.- Hop protein EC 2.7.1.112 Protein-Tyrosine Kinase IM Proc Natl Acad Sci U S A 2001 Nov 20;98(24):14186 Alleles Animal Carrier Proteins genetics physiology DNA-Binding Proteins antagonists & inhibitors Drosophila melanogaster embryology genetics metabolism Eye embryology ultrastructure Eye Abnormalities genetics Gene Expression Regulation, Developmental Insect Proteins genetics physiology Morphogenesis Mutagenesis, Insertional Neoplasms, Experimental genetics Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinase metabolism Proteins genetics physiology Recombination, Genetic Signal Transduction Support, U.S. Gov't, P.H.S. Trans-Activators antagonists & inhibitors FBrf0054767 91367265 1653906 1991 10 15 1991 10 15 2002 11 08

0028-0836 353 6340 1991 Sep 12 Role of the Drosophila patched gene in positional signalling. 184-7 After cellularization of the Drosophila embryo, positional differences within each primordial segment are maintained and elaborated by processes that require cell interactions. The best-documented examples of such intercellular signalling are the mutual interactions between neighbouring cells expressing the homeodomain protein engrailed and the secreted glycoprotein encoded by wingless, the Drosophila homologue of the murine Wnt-1 gene. Little is known about the molecular basis of these signalling mechanisms but the activities of several other genes, notably patched and hedgehog, have been implicated in the process. Here we show that the role of patched in positional signalling is permissive rather than instructive, its activity being required to suppress wingless transcription in cells predisposed to express the latter. According to this view, expression of wingless is normally maintained only in those cells receiving an extrinsic signal, encoded by hedgehog, that antagonizes the repressive activity of patched. We suggest that the patched protein may itself be the receptor for this signal, implying that this is an unusual mechanism of ligand-dependent receptor inactivation. ICRF Developmental Biology Unit, Department of Zoology, Oxford, UK. Ingham P W PW Taylor A M AM Nakano Y Y eng Journal Article

ENGLAND Nature 0410462 0 Glycoproteins 0 Insect Hormones 0 Membrane Proteins 0 Proteins 0 RNA, Messenger 0 Receptors, Cell Surface 0 patched protein, Drosophila IM Animal Cloning, Molecular Drosophila melanogaster embryology genetics Gene Expression Glycoproteins physiology Insect Hormones physiology Membrane Proteins physiology Morphogenesis Proteins physiology RNA, Messenger genetics Receptors, Cell Surface physiology Signal Transduction Transcription, Genetic FBrf0111499 99439600 10508657 1999 12 16 1999 12 16 2002 10 21

0955-0674 11 5 1999 Oct Genetic analysis of cadherin function in animal morphogenesis. 540-8 Cadherins are a superfamily of Ca(2+)-dependent adhesion molecules found in metazoans. Several classes of cadherins have been defined from which two - classic cadherins and Fat-like cadherins - have been studied by genetic approaches. Recent in vivo studies in Caenorhabditis elegans and Drosophila show that cadherins play an active role in a number of distinct morphogenetic processes. Classic cadherins function in epithelial polarization, epithelial sheet or tube fusion, cell migration, cell sorting, and axonal patterning. Fat-like cadherins are required for epithelial morphogenesis, proliferation control, and epithelial planar polarization. Department of Zoology University of Toronto 25 Harbord Street, Toronto, Ontario, M5S 3G5, Canada. utepass@zoo.utoronto.ca. Tepass U U eng Journal Article Review Review, Tutorial

UNITED STATES Curr Opin Cell Biol 8913428 0 Cadherins 0 Helminth Proteins 0 Insect Proteins 0 Membrane Proteins 0 dachsous protein, Drosophila 0 fat protein (cadherin) 7440-70-2 Calcium IM Animal Animals embryology genetics metabolism Cadherins chemistry genetics physiology Caenorhabditis elegans embryology physiology Calcium physiology Chordata, Nonvertebrate genetics metabolism Drosophila melanogaster embryology physiology Evolution, Molecular Helminth Proteins chemistry genetics physiology Human Insect Proteins chemistry genetics physiology Membrane Proteins genetics physiology Morphogenesis genetics Protein Conformation Protein Structure, Tertiary Species Specificity Structure-Activity Relationship Support, Non-U.S. Gov't 76 FBrf0085837 96125137 8575295 1996 03 11 1996 03 11 2002 11 01

0950-1991 121 12 1995 Dec The role of yan in mediating the choice between cell division and differentiation. 3947-58 An allele of the yan locus was isolated as an enhancer of the Ellipse mutation of the Drosophila epidermal growth factor receptor (Egfr) gene. This yan allele is an embryonic lethal and also fails to complement the lethality of anterior open (aop) mutations. Phenotypic and complementation analysis revealed that aop is allelic to yan and genetically the lethal alleles act as null mutations for the yan gene. Analysis of the lethal alleles in the embryo and in mitotic clones showed that loss of yan function causes cells to overproliferate in the dorsal neuroectoderm of the embryo and in the developing eye disc. Our studies suggest that the role of yan is defined by the developmental context of the cells in which it functions. An important role of this gene is in allowing a cell to choose between cell division and differentiation. The relationship of the Egfr and Notch pathways to this developmental role of yan is discussed. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles 90095, USA. Rogge R R Green P J PJ Urano J J Horn-Saban S S Mlodzik M M Shilo B Z BZ Hartenstein V V Banerjee U U eng 1RO1EY08152 EY NEI Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Eye Proteins 0 anterior open protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Alleles Animal Cell Differentiation genetics Cell Division genetics DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Embryonic Induction genetics Eye embryology Eye Proteins genetics Genes, Lethal Microscopy, Electron, Scanning Phenotype Receptor, Epidermal Growth Factor genetics Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0090470 97027631 8873754 1996 12 06 1996 12 06 2002 10 21

0012-1606 179 1 1996 Oct 10 daughterless is required for Drosophila photoreceptor cell determination, eye morphogenesis, and cell cycle progression. 65-78 Initiation of Drosophila peripheral nervous system (PNS) development requires the achaete-scute complex (AS-C) and the atonal (ato) genes. The AS-C and ato encode basic helix-loop-helix (bHLH) transcription factors that dimerize in vitro with another bHLH protein, daughterless (da). da has many functions during Drosophila embryonic development, as it is required for proper sex determination, oogenesis, and neurogenesis. Here, we examine the expression and function of da within the developing Drosophila eye. The use of a monoclonal antibody to the Da protein revealed that Da levels are modulated across the developing eye disc. Within the morphogenetic furrow (MF) and photoreceptor cell R8, there is a cell-by-cell correspondence between high levels of Da protein expression and Ato protein expression. Mosaic analysis of adult tissue demonstrates that da function is cell autonomous and required within R2, R3, R4, R5, and R8. Examination of gene expression in da- imaginal disc clones reveals that da regulates Ato expression in the MF, affects the progression of the MF, and is necessary for the reestablishment of the G2 and M phases of the synchronized cell cycle posterior to the MF. Howard Hughes Medical Institute and Bock Laboratories, Madison, Wisconsin 53706, USA. Brown N L NL Paddock S W SW Sattler C A CA Cronmiller C C Thomas B J BJ Carroll S B SB eng CA-07175 CA NCI Journal Article

UNITED STATES Dev Biol 0372762 0 DNA-Binding Proteins 0 Insect Hormones 0 Nuclear Proteins 0 Transcription Factors 0 ato protein 0 daughterless protein, Drosophila IM Animal Cell Cycle genetics DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Eye embryology Gene Expression Regulation, Developmental genetics Genes, Structural, Insect genetics Helix-Loop-Helix Motifs Insect Hormones genetics Microscopy, Phase-Contrast Morphogenesis genetics Nuclear Proteins genetics Photoreceptors, Invertebrate cytology embryology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors genetics Up-Regulation FBrf0068398 94170373 8124712 1994 04 08 1994 04 08 2002 10 31

0092-8674 76 4 1994 Feb 25 The role of specific protein-RNA and protein-protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. 735-46 We have investigated the function of different structural domains of the Drosophila splicing regulator Transformer 2 (Tra2). We find that the ribonucleoprotein consensus sequence (RNP-CS) of Tra2 is required for male fertility and positive and negative control of alternative splicing in transgenic flies, as well as for in vitro binding of recombinant Tra2 to doublesex and tra2 pre-mRNAs. Thus, all of the known functions of Tra2 require specific protein-RNA interactions. We also show that one of the two arginine-serine (RS)-rich domains of Tra2 is dispensable, while the other is essential for all of the in vivo functions. Part of this domain is also required for RNA binding in vitro. Significantly, the essential RS domain is also required for specific protein-protein interactions. We find that Tra2 interacts with itself, with the splicing regulator Transformer, and with the general splicing factor SF2 in vitro and in the yeast two-hybrid system. These results demonstrate that both protein-RNA and protein-protein interactions are involved in tra2-dependent activation and repression of alternative splicing. Howard Hughes Medical Institute, Columbia University, New York, New York 10032. Amrein H H Hedley M L ML Maniatis T T eng Journal Article

UNITED STATES Cell 0413066 0 DNA Primers 0 Nucleic Acid Precursors 0 RNA, Messenger 0 RNA-Binding Proteins 0 Ribonucleoproteins IM Cell. 1994 Feb 25;76(4):589-91 8124702 dsx tra2 Animal Base Sequence DNA Primers chemistry Drosophila melanogaster genetics Female Fertility Male Molecular Sequence Data Nucleic Acid Precursors metabolism Protein Binding RNA Splicing RNA, Messenger genetics RNA-Binding Proteins physiology Ribonucleoproteins physiology Sequence Deletion Sex Determination (Analysis) Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0101971 98190323 9529526 1998 04 23 1998 04 23 2000 12 18

0026-8925 257 4 1998 Feb Rearrangements at a hobo element inserted into the first intron of the singed gene in the unstable sn49 system of Drosophila melanogaster. 452-60 The cytological structure of the X chromosome and the DNA organisation of the singed locus were examined in five singed bristle mutants of Drosophila melanogaster. These mutants are all derived from the unstable mutant singed-49, isolated from a wild population in the Russian Far East in 1975. Rearrangements were found at a site within the first intron of the singed gene, where a hobo element is inserted in these mutants. One rearrangement, which is associated with a strong bristle phenotype, has an inversion between 2D and the location of singed at 7D, which separates the singed promoter from the singed coding region. Two phenotypically wild-type derivatives have smaller rearrangements within the first intron which do not appear to interfere with singed expression. Two derivatives with bristle phenotypes have more complex rearrangements, and one of them shows a dominant or antimorphic phenotype. DNA blotting and in situ hybridisation experiments show that, in addition to these rearrangements at a hobo element inserted at singed, other hobo elements in these strains have been mobilised. This system is therefore similar to others in which functional hobo elements continue to transpose, resulting in elevated rates of mutation and chromosome rearrangement. Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK. k.ohare@ic.ac.uk O'Hare K K Tam J L JL Lim J K JK Yurchenko N N NN Zakharov I K IK eng Journal Article

GERMANY Mol Gen Genet 0125036 0 Carrier Proteins 0 DNA Transposable Elements 0 Insect Proteins 146808-54-0 fascin 9007-49-2 DNA IM Animal Base Sequence Carrier Proteins genetics physiology DNA genetics DNA Transposable Elements genetics Drosophila melanogaster genetics ultrastructure In Situ Hybridization Insect Proteins genetics physiology Molecular Sequence Data Mutagenesis, Insertional Phenotype Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. X Chromosome genetics ultrastructure FBrf0090429 97070843 8913769 1997 03 06 1997 03 06 2000 12 18

0016-6731 144 3 1996 Nov Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. 1297-307 Both natural selection and mutational biases contribute to variation in codon usage bias within Drosophila species. This study addresses the cause of codon bias differences between the sibling species, Drosophila melanogaster and D. simulans. Under a model of mutation-selection-drift, variation in mutational processes between species predicts greater base composition differences in neutrally evolving regions than in highly biased genes. Variation in selection intensity, however, predicts larger base composition differences in highly biased loci. Greater differences in the G+C content of 34 coding regions than 46 intron sequences between D. melanogaster and D. simulans suggest that D. melanogaster has undergone a reduction in selection intensity for codon bias. Computer simulations suggest at least a fivefold reduction in Nes at silent sites in this lineage. Other classes of molecular change show lineage effects between these species. Rates of amino acid substitution are higher in the D. melanogaster lineage than in D. simulans in 14 genes for which outgroup sequences are available. Surprisingly, protein sizes are larger in D. melanogaster than in D. simulans in the 34 genes compared between the two species. A substantial fraction of silent, replacement, and insertion/deletion mutations in coding regions may be weakly selected in Drosophila. Section of Evolution and Ecology, University of California, Davis 95616, USA. hakashi@ucdavis.edu Akashi H H eng GENBANK M17827 M17828 M17830 M17831 M17832 M17833 M17834 M17835 M17836 M17837 M19547 M22210 M36581 M37837 X00607 X54116 X54120 X57361 X57362 X57363 X57364 X57365 X57366 X57367 X57368 X57369 X57370 X57371 X57372 X57373 Journal Article

UNITED STATES Genetics 0374636 0 Amino Acids 0 Codon 0 Proteins 9007-49-2 DNA IM Amino Acids Animal Base Sequence Codon DNA Drosophila genetics Drosophila melanogaster genetics Evolution, Molecular Models, Genetic Molecular Sequence Data Polymorphism (Genetics) Proteins Support, Non-U.S. Gov't FBrf0127389 20191741 10725244 2000 06 30 2000 06 30 2000 12 18

0950-1991 127 8 2000 Apr Drosophila atonal controls photoreceptor R8-specific properties and modulates both receptor tyrosine kinase and Hedgehog signalling. 1681-9 During Drosophila eye development, the proneural gene atonal specifies founding R8 photoreceptors of individual ommatidia, evenly spaced relative to one another in a pattern that prefigures ommatidial organisation in the mature compound eye. Beyond providing neural competence, however, it has remained unclear to what extent atonal controls specific R8 properties. We show here that reduced Atonal function gives rise to R8 photoreceptors that are functionally compromised: both recruitment and axon pathfinding defects are evident. Conversely, prolonged Atonal expression in R8 photoreceptors induces defects in inductive recruitment as a consequence of hyperactive EGFR signalling. Surprisingly, such prolonged expression also results in R8 pattern formation defects in a process associated with both Hedgehog and Receptor Tyrosine Kinase signalling. Our results strongly suggest that Atonal regulates signalling and other properties of R8 precursors. Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Edinburgh, EH9 3JR, UK. White N M NM Jarman A P AP eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Eye Proteins 0 Insect Proteins 0 Membrane Glycoproteins 0 ato protein 0 sevenless protein 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal DNA-Binding Proteins genetics metabolism Drosophila melanogaster genetics metabolism physiology Eye Proteins metabolism Female Gene Expression Helix-Loop-Helix Motifs Insect Proteins metabolism Male Membrane Glycoproteins metabolism Mutagenesis Photoreceptors, Invertebrate metabolism Receptor Protein-Tyrosine Kinases metabolism Receptor, Epidermal Growth Factor metabolism Signal Transduction Support, Non-U.S. Gov't FBrf0151904 22318817 12431377 2002 11 14 2003 01 03

1534-5807 3 5 2002 Nov Sequential activation of signaling pathways during innate immune responses in Drosophila. 711-22 Innate immunity is essential for metazoans to fight microbial infections. Genome-wide expression profiling was used to analyze the outcome of impairing specific signaling pathways after microbial challenge. We found that these transcriptional patterns can be dissected into distinct groups. We demonstrate that, in addition to signaling through the Toll and Imd pathways, signaling through the JNK and JAK/STAT pathways controls distinct subsets of targets induced by microbial agents. Each pathway shows a specific temporal pattern of activation and targets different functional groups, suggesting that innate immune responses are modular and recruit distinct physiological programs. In particular, our results may imply a close link between the control of tissue repair and antimicrobial processes. Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. Boutros Michael M Agaisse Hervé H Perrimon Norbert N eng Journal Article

United States Dev Cell 101120028 0 Lipopolysaccharides 0 Receptors, Steroid 0 Receptors, Thyroid Hormone 0 orphan nuclear receptor TR4 EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Animal Cell Line Drosophila melanogaster drug effects genetics immunology Gene Expression Profiling Genes, Insect Immunity, Natural Lipopolysaccharides pharmacology Mitogen-Activated Protein Kinases genetics Receptors, Steroid genetics Receptors, Thyroid Hormone genetics Signal Transduction Support, Non-U.S. Gov't Transcription, Genetic FBrf0092661 97225211 9071584 1997 07 24 1997 07 24 2002 11 01

0016-6731 145 2 1997 Feb Chromosomal homology and molecular organization of Muller's elements D and E in the Drosophila repleta species group. 281-95 Thirty-three DNA clones containing protein-coding genes have been used for in situ hybridization to the polytene chromosomes of two Drosophila repleta group species, D. repleta and D. buzzatii. Twenty-six clones gave positive results allowing the precise localization of 26 genes and the tentative identification of another nine. The results were fully consistent with the currently accepted chromosomal homologies and in no case was evidence for reciprocal translocations or pericentric inversions found. Most of the genes mapped to chromosomes 2 and 4 that are homologous, respectively, to chromosome arms 3R and 3L of D. melanogaster (Muller's elements E and D). The comparison of the molecular organization of-these two elements between D. melanogaster and D. repleta (two species that belong to different subgenera and diverged some 62 million years ago) showed an extensive reorganization via paracentric inversions. Using a maximum likelihood procedure, we estimated that 130 paracentric inversions have become fixed in element E after the divergence of the two lineages. Therefore, the evolution rate for element E is approximately one inversion per million years. This value is comparable to previous estimates of the rate of evolution of chromosome X and yields an estimate of 4.5 inversions per million years for the whole Drosophila genome. Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Spain. Ranz J M JM Segarra C C Ruiz A A eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Mapping Chromosomes Drosophila genetics Genes, Insect Hybridization, Genetic Inversion (Genetics) Polymorphism (Genetics) Support, Non-U.S. Gov't FBrf0054989 91288555 1905816 1991 08 02 1991 08 02 2000 12 18

0027-8424 88 13 1991 Jul 1 Zygotic genes that mediate torso receptor tyrosine kinase functions in the Drosophila melanogaster embryo. 5824-8 The developmental signal that specifies the fates of cells at the anterior and posterior termini of the Drosophila embryo is transmitted by the torso receptor tyrosine kinase. This paper presents the results of a genetic interaction test for zygotic loci that act downstream of torso in the terminal genetic hierarchy. Tests of 26 zygotic mutants with defects in terminal development indicate that at least 14 reside in this hierarchy. The phenotypes associated with these genes fall into three classes, each of which represents a distinct aspect of terminal development and evolution. Four of the genes have been molecularly cloned and their products include an intercellular communication factor and three kinds of transcription factors. Division of Biology, California Institute of Technology, Pasadena 91125. Strecker T R TR Yip M L ML Lipshitz H D HD eng HD23099 HD NICHD Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 EC 2.7.1.112 Protein-Tyrosine Kinase IM Kr S dpp flp fog grn gt hb hnt kkv kni knk lin pnt rho sdt sna sog tld tll tor tsg tup twi ush Animal Cell Differentiation Drosophila melanogaster embryology enzymology genetics Gene Expression Genes, Structural Morphogenesis Phenotype Protein-Tyrosine Kinase physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zygote FBrf0105193 99034369 9819060 1998 12 10 1998 12 10 2000 12 18

0026-8925 259 6 1998 Oct The Des-1 protein, required for central spindle assembly and cytokinesis, is associated with mitochondria along the meiotic spindle apparatus and with the contractile ring during male meiosis in Drosophila melanogaster. 664-73 Spermatogenesis in Drosophila melanogaster serves as an excellent model system for the isolation and analysis of genes required in the control of chromosome segregation and cytokinesis. We report here the isolation and molecular characterization of a novel P-element induced allele of the des-1 gene, which leads to male sterility as a consequence of the failure of central spindle assembly in meiotic spermatocytes and the formation of aberrant meiotic end products characteristic of cytokinesis failure. We have raised affinity-purified antibodies against a Des-1 fusion protein, and localized the Des-1 protein in Drosophila spermatocytes. We show that the Des- protein is colocalized with mitochondria throughout male meiosis, becoming intimately associated with mitochondria along the spindle apparatus during anaphase and telophase, and with the Nebenkern, or mitochondrial derivative, of the meiotic end products. In addition, a significant association of Des-1 with the contractile ring is observed during anaphase and telophase of meiosis. These observations, together with the presence of six potential transmembrane domains in the Des-1 protein, raise the possibility that Des-1 may act as part of an anchoring mechanism that links membrane-bounded cellular compartments to components of the cytoskeleton. Section of Genetics and Development, Cornell University, Ithaca, NY 14853, USA. jb39@cornell.edu Basu J J Li Z Z eng GM48430 GM NIGMS Journal Article

GERMANY Mol Gen Genet 0125036 0 Cell Cycle Proteins 0 Des-1 protein 0 Insect Proteins 0 Membrane Proteins IM Animal Cell Cycle genetics physiology Cell Cycle Proteins genetics metabolism Cell Division Drosophila melanogaster cytology genetics physiology Homozygote Insect Proteins genetics metabolism Larva Male Meiosis Membrane Proteins genetics metabolism Mitochondria genetics metabolism Mitotic Spindle Apparatus genetics Mutagenesis Restriction Mapping Spermatocytes cytology physiology Support, U.S. Gov't, P.H.S. FBrf0129984 20435740 10978289 2000 10 19 2000 10 19 2000 12 18

0016-6731 156 1 2000 Sep The shut-down gene of Drosophila melanogaster encodes a novel FK506-binding protein essential for the formation of germline cysts during oogenesis. 245-56 In Drosophila melanogaster, the process of oogenesis is initiated with the asymmetric division of a germline stem cell. This division results in the self-renewal of the stem cell and the generation of a daughter cell that undergoes four successive mitotic divisions to produce a germline cyst of 16 cells. Here, we show that shut-down is essential for the normal function of the germline stem cells. Analysis of weak loss-of-function alleles confirms that shut-down is also required at later stages of oogenesis. Clonal analysis indicates that shut-down functions autonomously in the germline. Using a positional cloning approach, we have isolated the shut-down gene. Consistent with its function, the RNA and protein are strongly expressed in the germline stem cells and in 16-cell cysts. The RNA is also present in the germ cells throughout embryogenesis. shut-down encodes a novel Drosophila protein similar to the heat-shock protein-binding immunophilins. Like immunophilins, Shut-down contains an FK506-binding protein domain and a tetratricopeptide repeat. In plants, high-molecular-weight immunophilins have been shown to regulate cell divisions in the root meristem in response to extracellular signals. Our results suggest that shut-down may regulate germ cell divisions in the germarium. Waksman Institute, Rutgers University, Piscataway, New Jersey 08854, USA. Munn K K Steward R R eng Journal Article

UNITED STATES Genetics 0374636 0 DNA, Complementary 0 Insect Proteins EC 5.2.1.- Immunophilins EC 5.2.1.- Tacrolimus Binding Proteins IM Alleles Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA, Complementary genetics Drosophila melanogaster cytology genetics metabolism Female Gene Expression Genes, Insect Immunophilins genetics In Situ Hybridization Insect Proteins genetics Molecular Sequence Data Oogenesis genetics Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Tacrolimus Binding Proteins FBrf0132265 21065972 11139274 2001 01 26 2001 06 21 2003 02 03

1350-9047 7 11 2000 Nov Molecular mechanisms of cell death and phagocytosis in Drosophila. 1027-34 The genetic tools available in Drosophila have facilitated our understanding of how apoptosis is regulated and executed in the context of the developing organism. All embryonic apoptosis is initiated by the activity of three genes, rpr, grim and hid. Each of these genes is independently regulated, allowing developmental apoptosis to be finely controlled. These initiators in turn activate the core apoptotic machinery, including the caspases. Drosophila counterparts to other conserved components of the apoptotic machinery have been recently identified, and we discuss how these may be integrated into the process of normal developmentally regulated cell death. We also outline the role that phagocytosis plays in the final stages of apoptosis and consider the molecular mechanisms guiding the elimination of apoptotic corpses. Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Bangs P P Franc N N White K K eng Journal Article Review Review, Tutorial

England Cell Death Differ 9437445 0 Insect Proteins 0 Neuropeptides 0 Peptides 0 grim protein, Drosophila 0 head involution defective protein 0 reaper peptide, Drosophila EC 3.4.22.- Caspases IM Animal Apoptosis Caspases metabolism Drosophila melanogaster embryology genetics growth & development physiology Human Insect Proteins genetics metabolism Mitochondria physiology Neuropeptides genetics metabolism Peptides genetics metabolism Phagocytosis 99 FBrf0093791 97290166 9144922 1997 05 29 1997 05 29 2003 06 16

0192-253X 20 2 1997 Localization of proteins to the apico-lateral junctions of Drosophila epithelia. 111-8 We have examined the distribution of proteins in the apico-lateral cell junctions in Drosophila imaginal discs. The subcellular distribution of these proteins in normal and mutant proliferating cells was analyzed with marker antibodies and confocal microscopy. Antibodies to phosphotyrosine (PY), Armadillo (Arm) and Drosophila E-cadherin (DE-cad) as well as FITC phalloidin marking filamentous actin, labeled the site of the adherens junction, whereas antibodies to Discs large (DIg), Fasciclin III (FasIII) and Coracle (Cor) labeled the more basal septate junction. The junctional proteins labeled by these antibodies underwent specific changes in distribution during the cell cycle. We have previously shown that a loss-of-function dlg mutation, which causes neoplastic imaginal disc overgrowth, leads to loss of the septate junctions and the formation of what appear to be ectopic adherens junctions [Woods et al., 1996]. We therefore extended this study to examine the effects of mutations in other genes that also cause imaginal disc overgrowth. Based on staining with PY and DIg antibodies, the apico-lateral junctional complexes appeared normal in tissue from the hyperplastic overgrowth mutants fat, dco, gd and wts. However, imaginal disc tissue from the neoplastic overgrowth mutants dlg and lgl showed abnormal distribution of the junctional markers including a complete loss of apico-basal polarity in loss-of-function dlg mutations. These results support the idea that some of the proteins of apico-lateral junctions are required both for apico-basal cell polarity and for the signalling mechanisms controlling cell proliferation, whereas others are required more specifically in cell-cell signalling. Developmental Biology Center, University of California, Irvine, USA. Woods D F DF Wu J W JW Bryant P J PJ eng CA-66263 CA NCI Journal Article

UNITED STATES Dev Genet 7909963 0 Cell Adhesion Molecules 0 Insect Proteins 0 Phosphoproteins 0 armadillo protein, Drosophila 0 lethal (2) giant larvae protein, Drosophila 143513-41-1 discs large 1 protein, Drosophila 21820-51-9 Phosphotyrosine IM Animal Cell Adhesion Molecules metabolism Cell Compartmentation Cell Membrane ultrastructure Cell Polarity Drosophila melanogaster embryology Epithelium ultrastructure Fluorescent Antibody Technique, Indirect Genes, Tumor Suppressor Insect Proteins metabolism physiology Intercellular Junctions ultrastructure Morphogenesis Phosphoproteins metabolism Phosphotyrosine metabolism Support, U.S. Gov't, P.H.S. Wing embryology FBrf0065519 94244482 8187645 1994 06 20 1994 06 20 2000 12 18

0950-1991 119 3 1993 Nov Sex-lethal, master and slave: a hierarchy of germ-line sex determination in Drosophila. 897-908 Female sex determination in the germ line of Drosophila melanogaster is regulated by genes functioning in the soma as well as genes that function within the germ line. Genes known or suspected to be involved in germ-line sex determination in Drosophila melanogaster have been examined to determine if they are required upstream or downstream of Sex-lethal+, a known germ-line sex determination gene. Seven genes required for female-specific splicing of germ-line Sex-lethal+ pre-mRNA are identified. These results together with information about the tissues in which these genes function and whether they control sex determination and viability or just sex determination in the germ line have been used to deduce the genetic hierarchy regulating female germ-line sex determination. This hierarchy includes the somatic sex determination genes transformer+, transformer-2+ and doublesex+ (and by inference Sex-lethal+), which control a somatic signal required for female germ-line sex determination, and the germ-line ovarian tumor genes fused+, ovarian tumor+, ovo+, sans fille+, and Sex-lethal+, which are involved in either the reception or interpretation of this somatic sex determination signal. The fused+, ovarian tumor+, ovo+ and sans fille+ genes function upstream of Sex-lethal+ in the germ line. Department of Biological Sciences, Stanford University, CA 94305. Oliver B B Kim Y J YJ Baker B S BS eng Journal Article

ENGLAND Development 8701744 0 DNA Primers IM Sx1 Animal Base Sequence DNA Primers Drosophila melanogaster embryology genetics Female Genes, Regulator physiology Genes, Structural, Neoplasm genetics Germ Cells physiology In Situ Hybridization Molecular Sequence Data Ovarian Neoplasms genetics Phenotype Polymerase Chain Reaction RNA Splicing Sex Differentiation genetics Support, Non-U.S. Gov't FBrf0043921 87051745 2877746 1987 01 14 1987 01 14 2000 12 18

0092-8674 47 5 1986 Dec 5 Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. 735-46 The sequence of paired, a pair-rule gene required for segmentation in Drosophila, is presented. A search for genes with domains homologous to the paired gene was initiated and three homologues from a set of 12 were characterized with respect to temporal or spatial expression and sequence homologies. All four are transcribed in early development, one in the oocyte and during cleavage stages in the form of a gradient. In addition to the prd-specific his-pro repeat, some of the 12 genes contain M-repeats and two new types of homeo boxes not detectable by hybridization with the two known classes of homeo boxes. The observed linking of gene sets through combinations of homologies coding for protein domains is consistent with a general network concept of gene action. Frigerio G G Burri M M Bopp D D Baumgartner S S Noll M M eng GENBANK K03517 K03518 K03519 M14548 M14549 M14550 M14551 Journal Article

UNITED STATES Cell 0413066 0 RNA, Messenger 24937-83-5 Poly A 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Comparative Study DNA genetics Drosophila melanogaster embryology genetics Genes, Homeobox Larva Poly A genetics RNA, Messenger genetics Repetitive Sequences, Nucleic Acid Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't FBrf0100564 98119836 9450933 1998 02 24 1998 02 24 2000 12 18

0890-9369 12 3 1998 Feb 1 Cooperative interactions between the central spindle and the contractile ring during Drosophila cytokinesis. 396-410 We analyzed male meiosis in mutants of the chickadee (chic) locus, a Drosophila melanogaster gene that encodes profilin, a low molecular weight actin-binding protein that modulates F-actin polymerization. These mutants are severely defective in meiotic cytokinesis. During ana-telophase of both meiotic divisions, they exhibit a central spindle less dense than wild type; certain chic allelic combinations cause almost complete disappearance of the central spindle. Moreover, chic mutant spermatocytes fail to form an actomyosin contractile ring. To further investigate the relationships between the central spindle and the contractile ring, we examined meiosis in the cytokinesis-defective mutants KLP3A and diaphanous and in testes treated with cytochalasin B. In all cases, we found that the central spindle and the contractile ring in meiotic ana-telophases were simultaneously absent. Together, these results suggest a cooperative interaction between elements of the actin-based contractile ring and the central spindle microtubules: When one of these structures is disrupted, the proper assembly of the other is also affected. In addition to effects on the central spindle and the cytokinetic apparatus, we observed another consequence of chic mutations: A large fraction of chic spermatocytes exhibit abnormal positioning and delayed migration of asters to the cell poles. A similar phenotype was seen in testes treated with cytochalasin B and has been noted previously in mutants at the twinstar locus, a gene that encodes a Drosophila member of the cofilin/ADF family of actin-severing proteins. These observations all indicate that proper actin assembly is necessary for centrosome separation and migration. Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Genetica e Biologia Molecolare, Universitá di Roma "La Sapienza," 00185 Rome, Italy. Giansanti M G MG Bonaccorsi S S Williams B B Williams E V EV Santolamazza C C Goldberg M L ML Gatti M M eng Journal Article

UNITED STATES Genes Dev 8711660 0 Actins 0 Contractile Proteins 0 Microfilament Proteins 0 profilin 0 twinstar protein IM Actins metabolism Anaphase physiology Animal Base Sequence Cell Division physiology Centrosome metabolism Contractile Proteins metabolism Drosophila melanogaster physiology Epistasis, Genetic Genes, Structural, Insect genetics Male Meiosis physiology Microfilament Proteins genetics metabolism physiology Microtubules metabolism Mitotic Spindle Apparatus metabolism Molecular Sequence Data Mutation genetics physiology Spermatogenesis physiology Support, Non-U.S. Gov't Telophase physiology Time Factors FBrf0105878 99053675 9839940 1998 12 22 1998 12 22 2001 11 02

0014-2956 257 3 1998 Nov 1 Identification of an essential gene encoding a class-V unconventional myosin in Drosophila melanogaster. 529-37 Class-V myosins are a unique type of myosin motor with roles in intracellular transport. The mouse dilute gene was the first member of this class to be cloned, with mutations resulting in lightening of the coat colour or neurogenic defects leading to early death. Further examples of class-V myosins have been described in yeast, chicken and rat. Here, we report the cloning of the first class-V myosin from Drosophila. We show that expression of this myosin is predominantly in the adult germ line and early embryo and that the transcript is localised in the oocyte during oogenesis. Genetic and in situ hybridisation experiments have determined that this gene is located in the 43C region. We have evidence that it maps to a mutation in this region with an embryonic lethal phenotype. Department of Biology, Eberly College of Science, Pennsylvania State University, USA. MacIver B B McCormack A A Slee R R Bownes M M eng GENBANK Y08160 Journal Article

GERMANY Eur J Biochem 0107600 0 DNA, Complementary 0 didum protein, Drosophila EC 3.6.1.4 Myosins IM Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA, Complementary Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Essential Molecular Sequence Data Myosins genetics Support, Non-U.S. Gov't FBrf0064423 93351853 8349112 1993 09 16 1993 09 16 2002 11 08

0016-6731 134 3 1993 Jul The 3' regulatory region of the Abdominal-B gene: genetic analysis supports a model of reiterated and interchangeable regulatory elements. 809-24 The Abdominal-B (Abd-B) gene is one of three genes in the bithorax complex, a cluster of homeotic genes in Drosophila. During embryogenesis Abd-B is expressed in a complex pattern, producing four different transcript classes, each of which exhibits a unique spatial pattern of expression. Proper regulation of the class A transcripts is required for appropriate development of the fifth through eighth abdominal segments and is mediated, in part, by a 60-kb regulatory region located 3' of the gene. We have isolated a new mutation, designated Abd-BCorset, which is caused by a deletion that leaves 15 kb of the 3' regulatory sequences immediately adjacent to the gene, but removes 45 kb of the more distant 3' regulatory elements. This mutation produces an unexpected homeotic segmental transformation of the fourth through seventh abdominal segments, and has been analyzed by genetic and molecular techniques. In situ hybridization to Abd-BCorset embryos shows a uniform and moderate level of the Abd-B class A transcript in the posterior abdomen, rather than the normal graded pattern of expression. Our analysis of the Abd-BCorset mutation has prompted a model of the 3' regulatory region of Abd-B based on reiterated cell type-specific elements controlled by adjacent position-sensitive activating elements. The gradient of Abd-B expression normally observed in the posterior abdomen appears to be achieved by varying the number of reiterated elements that are active in each segment. Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108. Crosby M A MA Lundquist E A EA Tautvydas R M RM Johnson J J JJ eng Journal Article

UNITED STATES Genetics 0374636 0 Abd-B proteins, Drosophila 0 Epoxy Compounds 0 Insect Hormones 0 Mutagens 0 RNA, Messenger 1464-53-5 erythritol anhydride IM Abd-B Animal Drosophila melanogaster genetics Epoxy Compounds Female Heterozygote Homozygote Insect Hormones genetics Male Multigene Family Mutagens RNA, Messenger metabolism Regulatory Sequences, Nucleic Acid Sequence Deletion Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0057335 92220163 1560824 1992 05 14 1992 05 14 2001 11 26

0028-0836 356 6369 1992 Apr 9 Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. 519-20 Two genomic regions with unusually low recombination rates in Drosophila melanogaster have normal levels of divergence but greatly reduced nucleotide diversity, apparently resulting from the fixation of advantageous mutations and the associated hitch-hiking effect. Here we show that for 20 gene regions from across the genome, the amount of nucleotide diversity in natural populations of D. melanogaster is positively correlated with the regional rate of recombination. This cannot be explained by variation in mutation rates and/or functional constraint, because we observe no correlation between recombination rates and DNA sequence divergence between D. melanogaster and its sibling species, D. simulans. We suggest that the correlation may result from genetic hitch-hiking associated with the fixation of advantageous mutants. Hitch-hiking thus seems to occur over a large fraction of the Drosophila genome and may constitute a major constraint on levels of genetic variation in nature. Section of Genetics and Development, Cornell University, Ithaca, New York 14853-2703. Begun D J DJ Aquadro C F CF eng Journal Article

ENGLAND Nature 0410462 IM Nature. 1992 Apr 9;356(6369):475-6 1560819 Adh DdcAmy Est-6 Gpdh Hsp70A Mtn-A N Pgd Pu Zw ci<up>/D</up> f oer ry su(f) v w y,ac z,tko Animal Drosophila melanogaster genetics Female Male Polymorphism (Genetics) Recombination, Genetic Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0137222 21384951 11493544 2001 08 08 2001 09 13 2002 04 19

0950-1991 128 12 2001 Jun fringe and Notch specify polar cell fate during Drosophila oogenesis. 2243-53 fringe encodes a glycosyltransferase that modulates the ability of the Notch receptor to be activated by its ligands. We describe studies of fringe function during early stages of Drosophila oogenesis. Animals mutant for hypomorphic alleles of fringe contain follicles with an incorrect number of germline cells, which are separated by abnormally long and disorganized stalks. Analysis of clones of somatic cells mutant for a null allele of fringe localizes the requirement for fringe in follicle formation to the polar cells, and demonstrates that fringe is required for polar cell fate. Clones of cells mutant for Notch also lack polar cells and the requirement for Notch in follicle formation appears to map to the polar cells. Ectopic expression of fringe or of an activated form of Notch can generate an extra polar cell. Our results indicate that fringe plays a key role in positioning Notch activation during early oogenesis, and establish a function for the polar cells in separating germline cysts into individual follicles. Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers The State University of New Jersey, Piscataway, NJ 08854, USA. Grammont M M Irvine K D KD eng R01-GM54594 GM NIGMS Journal Article

England Development 8701744 0 Membrane Proteins 0 Receptors, Cell Surface 0 notch protein EC 2.4 Glycosyltransferases EC 2.4.- fringe protein IM Animal Cell Differentiation Drosophila melanogaster metabolism Epithelium metabolism Female Gene Expression Glycosyltransferases genetics metabolism Membrane Proteins metabolism Mutagenesis Oogenesis physiology Ovarian Follicle cytology metabolism Ovary cytology metabolism Ovum cytology metabolism Receptors, Cell Surface metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0160543 22656482 12769862 2003 05 28 2003 07 11

1097-2765 11 5 2003 May Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA. 1397-404 The inhibition of male-specific lethal-2 (msl-2) mRNA translation in female flies is essential for X chromosome dosage compensation in Drosophila melanogaster. Translational repression of msl-2 requires sex-lethal (SXL) binding to uridine-rich sequences in both the 5' and 3' untranslated regions (UTRs) of the message. We delineate the msl-2 mRNA sequence elements that are important for regulation by SXL and identify functionally critical sequences adjacent to regulatory SXL binding sites. We demonstrate that SXL inhibits translation initiation and prevents the stable association of the 40S ribosomal subunit with the mRNA in a manner that does not require the presence of a cap structure at the 5' end of the mRNA. These results elucidate a critical regulatory step for dosage compensation in Drosophila melanogaster. European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. Gebauer Fátima F Grskovic Marica M Hentze Matthias W MW eng Journal Article

United States Mol Cell 9802571 0 3' Untranslated Regions 0 5' Untranslated Regions 0 Drosophila Proteins 0 Nuclear Proteins 0 RNA Cap-Binding Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 Repressor Proteins 0 Sxl protein, Drosophila 0 Transcription Factors 0 male-specific lethal-2 protein IM 3' Untranslated Regions genetics 5' Untranslated Regions genetics Animal Binding Sites genetics Dosage Compensation (Genetics) Drosophila Proteins genetics metabolism Drosophila melanogaster genetics Female Genes, Lethal genetics Male Nuclear Proteins genetics metabolism RNA Cap-Binding Proteins genetics metabolism RNA, Messenger genetics RNA-Binding Proteins genetics metabolism Repressor Proteins genetics metabolism Ribosomes genetics metabolism Support, Non-U.S. Gov't Transcription Factors genetics metabolism Translation, Genetic genetics X Chromosome genetics FBrf0107330 99159003 10047521 1999 03 16 1999 03 16 2001 11 02

0955-0674 11 1 1999 Feb Molecular genetic approaches to understanding the actin cytoskeleton. 142-51 New tools in molecular genetics, such as genetic interaction screens and conditional gene targeting, have advanced the study of actin dynamics in a number of model systems. Yeast, Dictyostelium, Caenorhabditis elegans, Drosophila, and mice have contributed much in recent years to a better understanding of both the numerous functions and modes of regulation of the actin cytoskeleton. European Molecular Biology Laboratory Mouse Biology Programme via Ramarini 32 00016 Monterotondo Italy. sutherland@embl-monterotondo.it Sutherland J D JD Witke W W eng Journal Article Review Review, Tutorial

UNITED STATES Curr Opin Cell Biol 8913428 0 Actins 0 Gelsolin 0 Microfilament Proteins 0 profilin EC 3.6.1.4 Myosins IM Actins physiology Animal Caenorhabditis elegans Cell Division physiology Cytoskeleton physiology Dictyostelium Drosophila melanogaster Endocytosis physiology Gelsolin metabolism Genetic Techniques Mice Microfilament Proteins metabolism Myosins metabolism Signal Transduction Support, Non-U.S. Gov't 103 FBrf0107369 99126439 9927464 1999 03 09 1999 03 09 2000 12 18

0016-6731 151 2 1999 Feb The gene search system. A method for efficient detection and rapid molecular identification of genes in Drosophila melanogaster. 725-37 We have constructed a P-element-based gene search vector for efficient detection of genes in Drosophila melanogaster. The vector contains two copies of the upstream activating sequence (UAS) enhancer adjacent to a core promoter, one copy near the terminal inverted repeats at each end of the vector, and oriented to direct transcription outward. Genes were detected on the basis of phenotypic changes caused by GAL4-dependent forced expression of vector-flanking DNA, and the transcripts were identified with reverse transcriptase PCR (RT-PCR) using the vector-specific primer and followed by direct sequencing. The system had a greater sensitivity than those already in use for gain-of-function screening: 64% of the vector insertion lines (394/613) showed phenotypes with forced expression of vector-flanking DNA, such as lethality or defects in adult structure. Molecular analysis of 170 randomly selected insertions with forced expression phenotypes revealed that 21% matched the sequences of cloned genes, and 18% matched reported expressed sequence tags (ESTs). Of the insertions in cloned genes, 83% were upstream of the protein-coding region. We discovered two new genes that showed sequence similarity to human genes, Ras-related protein 2 and microsomal glutathione S-transferase. The system can be useful as a tool for the functional mapping of the Drosophila genome. Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, USA. Toba G G Ohsako T T Miyata N N Ohtsuka T T Seong K H KH Aigaki T T eng Journal Article

UNITED STATES Genetics 0374636 0 Genetic Vectors IM Amino Acid Sequence Animal Drosophila melanogaster genetics Genes, Insect Genetic Vectors Human Molecular Sequence Data Polymerase Chain Reaction methods Sequence Alignment Sequence Analysis, DNA methods Support, Non-U.S. Gov't FBrf0151255 22105637 12110163 2002 07 11 2002 08 12

1534-5807 3 1 2002 Jul Dynamic analysis of dorsal closure in Drosophila: from genetics to cell biology. 9-19 Throughout development a series of epithelial bendings, sweepings, and fusions occur that collectively give shape to the embryo. These morphogenetic movements are driven by coordinated assembly and contraction of the actomyosin cytoskeleton in restricted populations of epithelial cells. One well-studied example of such a morphogenetic episode is dorsal closure in Drosophila embryogenesis. This process is tractable at a genetic level and has recently become the focus of live cell biology analysis because of the availability of flies expressing GFP-fusion proteins. This marriage of genetics and cell biology is very powerful and is allowing the dissection of fundamental signaling mechanisms that regulate the cytoskeletal reorganizations and contractions underlying coordinated tissue movements in the embryo. Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156, Oeiras, Portugal. ajacinto@igc.gulbenkian.pt Jacinto Antonio A Woolner Sarah S Martin Paul P eng Journal Article Review Review, Tutorial

United States Dev Cell 101120028 0 Actins EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase EC 3.6.1.- rho GTP-Binding Proteins IM Actins metabolism ultrastructure Animal Body Patterning physiology Cell Communication physiology Cytoskeleton metabolism ultrastructure Drosophila melanogaster embryology metabolism ultrastructure Embryo embryology metabolism ultrastructure Epithelial Cells metabolism ultrastructure Gene Expression Regulation, Developmental physiology Mitogen-Activated Protein Kinases genetics metabolism Support, Non-U.S. Gov't rho GTP-Binding Proteins genetics metabolism 91 FBrf0076485 95047428 7958947 1994 12 01 1994 12 01 2001 11 02

0378-1119 148 2 1994 Oct 21 Induction of a mirror-image duplication of anterior wing structures by localized hedgehog expression in the anterior compartment of Drosophila melanogaster wing imaginal discs. 211-7 The segment polarity gene hedgehog (hh) encodes a secretory protein involved in cell-cell communication in Drosophila melanogaster. The hh gene is expressed in the posterior compartment and is essential for the establishment and maintenance of the anterior/posterior-compartment boundary of each embryonic parasegment [Ingham, P.W., Nature 366 (1993) 560-562]. To clarify possible hh functions in adult appendage formation, we isolated a fly line (h9D) associated with a wing malformation from among fly lines with an hh transgene whose expression is under the control of trapped enhancers. In h9D flies, the ectopic expression of hh occurred in the anterior edge of wing pouch in the wing disc. This abnormal hh expression resulted in not only a mirror-image duplication and ectopic outgrowth in the anterior wing compartment, but also the ectopic expression of patched and decapentaplegic, strongly suggesting that the hh product serves as a morphogen or an inducer essential for wing development, including the proximal/distal axis formation. Department of Biophysics and Biochemistry, School of Science, University of Tokyo, Japan. Kojima T T Michiue T T Orihara M M Saigo K K eng Journal Article

NETHERLANDS Gene 7706761 0 Proteins 149291-21-4 hedgehog protein, Drosophila IM hh Animal Animals, Genetically Modified Drosophila melanogaster genetics growth & development Female Gene Dosage Male Phenotype Proteins genetics Support, Non-U.S. Gov't Wing growth & development FBrf0111808 20042298 10572053 2000 01 21 2000 01 21 2002 11 01

0950-1991 126 24 1999 Dec Recombination and disjunction in female germ cells of Drosophila depend on the germline activity of the gene sex-lethal. 5785-94 Gametogenesis in males and females differs in many ways. An important difference in Drosophila is that recombination between homologous chromosomes occurs only in female meiosis. Here, we report that this process relies on the correct functioning of Sex-lethal (Sxl) which is primarily known as the master gene in somatic sex determination. Certain alleles of this gene (Sxl(fs)) disrupt the germline, but not the somatic function of Sxl and cause an arrest of germ cell development during cystocyte proliferation. Using dominant suppressor mutations that relieve this early block in Sxl(fs) mutant females, we discovered additional requirements of Sxl for normal meiotic differentiation of the oocyte. Females mutant for Sxl(fs) and carrying a suppressor become fertile, but pairing of homologous chromosomes and formation of chiasmata is severely perturbed, resulting in an almost complete lack of recombinants and a high incidence of non-disjunction events. Similar results were obtained when germline expression of wild-type Sxl was compromised by mutations in virilizer (vir), a positive regulator of Sxl. Ectopic expression of a Sxl transgene in premeiotic stages of male germline development, on the other hand, is not sufficient to allow recombination to take place, which suggests that Sxl does not have a discriminatory role in this female-specific process. We propose that Sxl performs at least two tasks in oogenesis: an 'early' function in formation of the egg chamber, and a 'late' function in progression of the meiotic cell cycle, suggesting that both events are coordinated by a common mechanism. Zoological Institute of the University Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. dbopp@zool.unizh.ch Bopp D D Schütt C C Puro J J Huang H H Nöthiger R R eng Journal Article

ENGLAND Development 8701744 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Animal Cell Nucleus Chromosome Segregation Drosophila melanogaster genetics physiology Female Fertility Male Meiosis physiology Mutagenesis Nondisjunction, Genetic Oocytes physiology Ovum physiology RNA-Binding Proteins genetics physiology Recombination, Genetic Spermatozoa physiology Support, Non-U.S. Gov't FBrf0155865 22453712 12551951 2003 02 04 2003 03 12

0021-9525 160 3 2003 Feb 3 Drosophila p120catenin plays a supporting role in cell adhesion but is not an essential adherens junction component. 433-49 Cadherin-catenin complexes, localized to adherens junctions, are essential for cell-cell adhesion. One means of regulating adhesion is through the juxtamembrane domain of the cadherin cytoplasmic tail. This region is the binding site for p120, leading to the hypothesis that p120 is a key regulator of cell adhesion. p120 has also been suggested to regulate the GTPase Rho and to regulate transcription via its binding partner Kaiso. To test these hypothesized functions, we turned to Drosophila, which has only a single p120 family member. It localizes to adherens junctions and binds the juxtamembrane region of DE-cadherin (DE-cad). We generated null alleles of p120 and found that mutants are viable and fertile and have no substantial changes in junction structure or function. However, p120 mutations strongly enhance mutations in the genes encoding DE-cadherin or Armadillo, the beta-catenin homologue. Finally, we examined the localization of p120 during embryogenesis. p120 localizes to adherens junctions, but its localization there is less universal than that of core adherens junction proteins. Together, these data suggest that p120 is an important positive modulator of adhesion but that it is not an essential core component of adherens junctions. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Myster Steven H SH Cavallo Robert R Anderson Charles T CT Fox Donald T DT Peifer Mark M eng GM19888 GM NIGMS R01 GM47857 GM NIGMS Journal Article 2003 01 27

United States J Cell Biol 0375356 0 Cadherins 0 Cell Adhesion Molecules 0 DNA, Complementary 0 Drosophila Proteins 0 Phosphoproteins 0 Trans-Activators 0 armadillo protein, Drosophila 0 cadherin-associated Src substrate p120 IM Adherens Junctions genetics metabolism Animal Cadherins genetics metabolism Cell Adhesion genetics Cell Adhesion Molecules deficiency genetics Cell Membrane genetics metabolism DNA, Complementary analysis genetics Drosophila Proteins genetics metabolism Drosophila melanogaster cytology embryology metabolism Embryo, Nonmammalian abnormalities cytology metabolism Evolution, Molecular Female Male Molecular Sequence Data Mutation genetics Phosphoproteins deficiency genetics Phylogeny Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism FBrf0052663 90231469 1691829 1990 05 31 1990 05 31 2001 11 26

0028-0836 345 6270 1990 May 3 Mediation of meiotic and early mitotic chromosome segregation in Drosophila by a protein related to kinesin. 81-3 Contrary to the traditional view that microtubules pull chromosomes polewards during the anaphase stage of meiotic and mitotic cell divisions, new evidence suggests that the chromosome movements are driven by a motor located at the kinetochore. The process of chromosome segregation involves proper arrangement of kinetochores for spindle attachment, followed by spindle attachment and chromosome movement. Mechanisms in Drosophila for chromosome segregation in meiosis differ in males and females, implying the action of different gene products in the two sexes. A product encoded at the claret locus in Drosophila is required for normal chromosome segregation in meiosis in females and in early mitotic divisions of the embryo. Here we show that the predicted amino-acid sequence of this product is related to the heavy chain of kinesin. The conserved region corresponds to the kinesin motor domain and includes the ATP-binding site and a region that can bind microtubules. A second region contains a leucine repeat motif which may mediate protein-subunit interactions necessary for attachment of chromosomes to the spindle. The mutant phenotype of chromosome nondisjunction and loss, and its similarity to the kinesin ATP-binding domain, suggest that the product encoded at claret not only stabilizes chromosome attachments to the spindle, but may also be a motor that drives chromosome segregation in female meiosis. Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710. Endow S A SA Henikoff S S Soler-Niedziela L L eng GENBANK X52814 Journal Article

ENGLAND Nature 0410462 0 Insect Hormones 0 Microtubule-Associated Proteins 0 claret segregation protein 63231-63-0 RNA 9007-49-2 DNA EC 3.6.1.- Kinesin EC 3.6.1.3 Adenosinetriphosphatase IM Nature. 1990 May 3;345(6270):22-3 2139498 Adenosinetriphosphatase genetics physiology Amino Acid Sequence Animal Base Sequence Chromosomes physiology Cloning, Molecular DNA genetics Drosophila melanogaster genetics Female Insect Hormones genetics Kinesin Male Meiosis genetics Microtubule-Associated Proteins genetics Microtubules physiology Mitosis genetics Mitotic Spindle Apparatus physiology Molecular Sequence Data Mutation RNA genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0054813 91097817 1702651 1991 02 21 1991 02 21 2001 11 02

0896-6273 6 1 1991 Jan cAMP-dependent protein kinase and the disruption of learning in transgenic flies. 71-82 A molecular genetic approach was used to test for a role of cAMP-dependent protein kinase (PKA) in learning and memory in Drosophila. We used genes encoding a peptide inhibitor of PKA, an N-terminal regulatory subunit fragment containing a pseudosubstrate inhibitory domain, and a wild-type catalytic subunit. These dominantly acting genes were placed under control of the hsp70 promoter and transformed into wild-type flies. Induction of the transgenes by 1 hr heat shock results in overproduction of their RNA in adult flies. The same heat shock treatment disrupts the ability of the flies to learn in an odor discrimination task reinforced with electric shock. The results demonstrate the involvement of PKA in the associative learning of Drosophila. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139. Drain P P Folkers E E Quinn W G WG eng Journal Article

UNITED STATES Neuron 8809320 0 Carrier Proteins 0 protein kinase modulator 60-92-4 Cyclic AMP 63231-63-0 RNA EC 2.7.1.37 Protein Kinases IM Animal Animals, Genetically Modified Carrier Proteins pharmacology Catalysis Cyclic AMP pharmacology Drosophila melanogaster genetics physiology Electroshock Gene Expression Genes, Regulator Learning physiology Memory physiology Mutagenesis Protein Kinases genetics physiology RNA genetics Smell Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transformation, Genetic FBrf0084011 96019052 7587594 1995 12 06 1995 12 06 2000 12 18

0009-5915 104 1 1995 Oct Polytene chromosomes show normal gene activity but some mRNAs are abnormally accumulated in the pseudonurse cell nuclei of Drosophila melanogaster otu mutants. 44-55 Certain mutant alleles of the ovarian tumor (otu) locus give rise to polytene chromosomes in the pseudonurse cells (PNCs). We have previously shown that the banding pattern of these germ line-derived chromosomes is similar to that in the larval salivary gland chromosomes. In this study, we have examined the gene activity of these chromosomes. General gene expression from these chromosomes was studied by uridine autoradiography. The expression of specific genes was monitored by in situ hybridisation to mRNA and also by combining enhancer trap lines with otu mutants. We found that most of the genes studied were expressed in the PNCs as they were in the wild-type nurse cells. Four out of the 12 mRNAs studied accumulated in the nuclei instead of migrating to the cytoplasm. The intensity of accumulation directly correlated with the extent of polytenisation in the PNC nuclei. We suggest that the otu mRNA remains partly attached to the polytene chromosome template after transcription and discuss the effects of this phenomenon on polytenisation of the PNC chromosomes. Department of Biosciences, Division of Genetics, P.O. Box 56, FIN-00014 University of Helsinki, Finland. Heino T I TI Lahti V P VP Tirronen M M Roos C C eng Journal Article

GERMANY Chromosoma 2985138R 0 RNA, Messenger IM Animal Cell Nucleus metabolism ultrastructure Chromosomes genetics ultrastructure Drosophila melanogaster genetics Female Gene Expression Regulation In Situ Hybridization Mutation Ovary cytology RNA, Messenger metabolism Transcription, Genetic FBrf0052550 90258853 1692958 1990 06 25 1990 06 25 2000 12 18

0270-7306 10 6 1990 Jun Biochemical characterization of the Drosophila dpp protein, a member of the transforming growth factor beta family of growth factors. 2669-77 The decapentaplegic (dpp) gene of Drosophila melanogaster is required for pattern formation in the embryo and for viability of the epithelial cells in the imaginal disks. The dpp protein product predicted from the DNA sequence is similar to members of a family of growth factors that includes transforming growth factor beta (TGF-beta). We have produced polyclonal antibodies to a recombinant dpp protein made in bacteria and used a metallothionein promoter to express a dpp cDNA in Drosophila S2 cells. Similar to other proteins in the TGF-beta family, the dpp protein produced by the Drosophila cells was proteolytically cleaved, and both portions of the protein were secreted from the cells. The amino-terminal 47-kilodalton (kDa) peptide was found in the medium and in the proteins adhering to the plastic petri dish. The carboxy-terminal peptide, the region with sequence similarity to the active ligand portion of TGF-beta, was found extracellularly as a 30-kDa homodimer. Most of the 30-kDa homodimer was in the S2 cell protein adsorbed onto the surface of the plastic dish. The dpp protein could be released into solution by increased salt concentration and nonionic detergent. Under these conditions, the amino-terminal and carboxy-terminal portions of dpp were not associated in a stable complex. McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706. Panganiban G E GE Rashka K E KE Neitzel M D MD Hoffmann F M FM eng CAD7175 CA NCI GM07215 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Growth Substances 0 Insect Hormones 0 Macromolecular Systems 0 Plasmids 0 dpp protein, Drosophila 63231-63-0 RNA 76057-06-2 Transforming Growth Factors IM Amino Acid Sequence Animal Blotting, Western Cell Line Clone Cells Comparative Study Drosophila melanogaster genetics Growth Substances genetics Insect Hormones genetics isolation & purification metabolism Macromolecular Systems Molecular Sequence Data Molecular Weight Plasmids RNA isolation & purification Restriction Mapping Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transforming Growth Factors genetics FBrf0048653 88246433 2454394 1988 07 25 1988 07 25 2000 12 18

0270-7306 8 4 1988 Apr Tissue localization of Drosophila melanogaster insulin receptor transcripts during development. 1638-47 The Drosophila melanogaster insulin receptor (Drosophila insulin receptor homolog [dIRH]) is similar to its mammalian counterpart in deduced amino acid sequence, subunit structure, and ligand-stimulated protein tyrosine kinase activity. The function of this receptor in D. melanogaster is not yet known. However, a role in development is suggested by the observations that levels of insulin-stimulated kinase activity and expression of dIRH mRNA are maximal during Drosophila midembryogenesis. In this study, a 2.9-kilobase (kb) cDNA clone corresponding to both the dIRH tyrosine kinase domain and some of the 3' untranslated sequence was used to determine the tissue distribution of dIRH mRNA during development. Two principal mRNAs of 11 and 8.6 kb hybridized with the dIRH cDNA in Northern (RNA) blot analysis. The abundance of the 8.6-kb mRNA increased transiently in early embryos, whereas the 11-kb species was most abundant during midembryogenesis. A similar pattern of expression was previously determined by Northern analysis, using a dIRH genomic clone (L. Petruzzelli, R. Herrera, R. Arenas-Garcia, R. Fernandez, M. J. Birnbaum, and O. M. Rosen, Proc. Natl. Acad. Sci. USA 83:4710-4714, 1986). In situ hybridization revealed dIRH transcripts in the ovaries of adult flies, in which the transcripts appeared to be synthesized by nurse cells for eventual storage as maternal RNA in the mature oocyte. Throughout embryogenesis, dIRH transcripts were ubiquitously expressed, although after midembryogenesis, higher levels were detected in the developing nervous system. Nervous system expression remained elevated throughout the larval stages and persisted in the adult, in which the cortex of the brain and ganglion cells were among the most prominently labeled tissues. In larvae, the imaginal disk cells exhibited comparatively high levels of dIRH mRNA expression. The broad distribution of dIRH mRNA in embryos and imaginal disks is compatible with a role for dIRH in anabolic processes required for cell growth. The apparently elevated expression of dIRH mRNA in nervous tissue during mid- and late embryogenesis coincides with a period of active neurite outgrowth and suggests that dIRH may be involved in this process. Program in Molecular Biology, Memorial Sloan-Kettering Cancer Research Center, New York, New York. Garofalo R S RS Rosen O M OM eng 5R37-DK35158 DK NIDDK Journal Article

UNITED STATES Mol Cell Biol 8109087 0 RNA, Antisense 0 RNA, Messenger 63231-63-0 RNA EC 2.7.1.112 Receptor, Insulin EC 3.1.21 DNA Restriction Enzymes IM Animal Cloning, Molecular DNA Restriction Enzymes Drosophila melanogaster genetics growth & development metabolism Female Genes, Structural Male Nucleic Acid Hybridization Organ Specificity RNA genetics RNA, Antisense RNA, Messenger antagonists & inhibitors genetics Receptor, Insulin genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0127077 20213667 10748461 2000 06 21 2000 06 21 2001 12 07

1526-954X 26 4 2000 Apr Temperature-dependent gene silencing by an expressed inverted repeat in Drosophila. 240-4 Posttranscriptional gene silencing (PTGS) induced by double-stranded RNA (dsRNA) is an intriguing phenomenon that has been observed in a variety of organisms, including Drosophila melanogaster. Although PTGS in Drosophila is typically observed following direct injection of the dsRNA into embryos, it is theoretically possible that the in vivo transcription of an inverted repeat transgene might also produce a dsRNA "hairpin" that is capable of triggering PTGS. Here we test this idea, and show that an expressed inverted repeat of a portion of the sex differentiation gene, transformer-2, (tra-2), driven by a GAL4-dependent promoter, does genetically repress the endogenous wild-type tra-2 function, producing a dominant loss-of-function mutant phenotype. Remarkably, this effect is temperature-sensitive, with phenotypic consequences seen at 29 degrees, but not at 22 degrees. Moreover, by altering the dosage of either the transgenes or the endogenous tra2(+) loci, one can vary the effect over a wide range of mutant phenotypes. Department of Biology, Syracuse University, Syracuse, New York, USA. Fortier E E Belote J M JM eng Journal Article

UNITED STATES Genesis 100931242 0 Ribonucleoproteins 0 transformer-2 protein IM Genesis;2000 May;27(1):48 Animal Drosophila melanogaster genetics Gene Silencing Genes, Insect Polymerase Chain Reaction Repetitive Sequences, Nucleic Acid Ribonucleoproteins genetics Support, U.S. Gov't, Non-P.H.S. FBrf0103253 98252816 9584125 1998 07 30 1998 07 30 2002 11 01

0950-1991 125 12 1998 Jun Identifying loci required for follicular patterning using directed mosaics. 2263-71 We have developed a 'directed mosaic' system in Drosophila by using the GAL4 system to control the expression of the yeast recombinase, FLP, in a spatial and temporal fashion. By directing FLP expression, we show that it is possible to efficiently and specifically target loss-of-function studies for vital loci to the developmental pathway of interest. A simple F1 adult phenotypic screen demonstrated that most adult tissues can be analyzed with this approach. Using GAL4 lines expressed during oogenesis, we have refined the system to examine the roles of vital loci in the development of the follicular epithelium. We have identified essential genes involved in egg chamber organization, cell migration and cell shape. Further, we have used this technique to gain insights into the role of the Drosophila EGF receptor pathway in establishing the egg axes. Finally, using different UAS-FLP, GAL4 and existing FRT lines, we have built stocks that permit the analysis of approximately 95% of the genome in follicular mosaics. Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, MA 02115, USA. Duffy J B JB Harrison D A DA Perrimon N N eng Journal Article

ENGLAND Development 8701744 0 GAL4 protein, S cerevisiae 0 Transcription Factors EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.7.- DNA Nucleotidyltransferases EC 2.7.7.- FLP recombinase IM Animal Body Patterning DNA Nucleotidyltransferases genetics metabolism Drosophila melanogaster embryology genetics Female Genes, Insect Mitosis Mosaicism Oogenesis Ovarian Follicle embryology Phenotype Receptor Protein-Tyrosine Kinases metabolism Receptor, Epidermal Growth Factor metabolism Recombination, Genetic Signal Transduction Support, Non-U.S. Gov't Transcription Factors genetics physiology FBrf0087003 96189078 8628263 1996 06 21 1996 06 21 2000 12 18

0270-7306 16 5 1996 May Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster. 1966-77 We report the molecular and genetic characterization of the cytoplasmic dynein light-chain gene, ddlc1, from Drosophila melanogaster. ddlc1 encodes the first cytoplasmic dynein light chain identified, and its genetic analysis represents the first in vivo characterization of cytoplasmic dynein function in higher eucaryotes. The ddlc1 gene maps to 4E1-2 and encodes an 89-amino-acid polypeptide with a high similarity to the axonemal 8-kDa outer-arm dynein light chain from Chlamydomonas flagella. Developmental Northern (RNA) blot analysis and ovary and embryo RNA in situ hybridizations indicate that the ddlc1 gene is expressed ubiquitously. Anti-DDLC1 antibody analyses show that the DDLC1 protein is localized in the cytoplasm. P-element-induced partial-loss-of-function mutations cause pleiotropic morphogenetic defects in bristle and wing development, as well as in oogenesis, and hence result in female sterility. The morphological abnormalities found in the ovaries are always associated with a loss of cellular shape and structure, as visualized by a disorganization of the actin cytoskeleton. Total-loss-of-function mutations cause lethality. A large proportion of mutant animals degenerate during embryogenesis, and the dying cells show morphological changes characteristic of apoptosis, namely, cell and nuclear condensation and fragmentation, as well as DNA degradation. Cloning of the human homolog of the ddlc1 gene, hdlc1, demonstrates that the dynein light-chain 1 is highly conserved in flies and humans. Northern blot analysis and epitope tagging show that the hdlc1 gene is ubiquitously expressed and that the human dynein light chain 1 is localized in the cytoplasm. hdlc1 maps to 14q24. Institute of Molecular and Cell Biology, National University of Singapore. Dick T T Ray K K Salz H K HK Chia W W eng GENBANK U32855 U32944 Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA Primers EC 3.6.1.33 Dynein ATPase IM Alleles Amino Acid Sequence Animal Base Sequence Blotting, Northern Chlamydomonas physiology Chromosome Mapping Comparative Study Cytoplasm metabolism DNA Primers Drosophila melanogaster embryology genetics physiology Dynein ATPase biosynthesis genetics Embryo, Nonmammalian cytology physiology Female Flagella physiology Gene Expression Regulation, Developmental Genes, Insect Human Infertility, Female Molecular Sequence Data Morphogenesis genetics Mutagenesis, Insertional Ovary physiology Polymerase Chain Reaction Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0160869 22719040 12835388 2003 07 01 2003 09 30

0950-1991 130 16 2003 Aug Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups. 3715-24 EGF receptor signalling plays diverse inductive roles during development. To achieve this, its activity must be carefully regulated in a variety of ways to control the time, pattern, intensity and duration of signalling. We show that the cell surface protein Echinoid is required to moderate Egfr signalling during R8 photoreceptor selection by the proneural gene atonal during Drosophila eye development. In echinoid mutants, Egfr signalling is increased during R8 formation, and this causes isolated R8 cells to be replaced by groups of two or three cells. This mutant phenotype resembles the normal inductive function of Egfr in other developmental contexts, particularly during atonal-controlled neural recruitment of chordotonal sense organ precursors. We suggest that echinoid acts to prevent a similar inductive outcome of Egfr signalling during R8 selection. Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Edinburgh EH9 3JR, Scotland, UK. Rawlins Emma L EL White Neil M NM Jarman Andrew P AP eng Journal Article

England Development 8701744 0 Cell Adhesion Molecules 0 DNA-Binding Proteins 0 Drosophila Proteins 0 ED protein, Drosophila 0 Recombinant Fusion Proteins 0 Repressor Proteins 0 ato protein 0 echinoid protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Cell Adhesion Molecules genetics metabolism DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster growth & development Genes, Reporter Morphogenesis Mutation Neurons cytology physiology Phenotype Photoreceptors, Invertebrate growth & development metabolism ultrastructure Receptor, Epidermal Growth Factor metabolism Recombinant Fusion Proteins metabolism Repressor Proteins genetics metabolism Signal Transduction physiology Support, Non-U.S. Gov't FBrf0042061 86028184 3931920 1985 12 02 1985 12 02 2000 12 18

0092-8674 42 3 1985 Oct A small region on the X chromosome of Drosophila regulates a key gene that controls sex determination and dosage compensation. 877-87 In Drosophila, flies with two X chromosomes are females, with one X chromosome, males. We investigated the presence of sex determining factors on the X chromosome by constructing genotypes with one X and various X-chromosomal duplications. We found that female determining factors are not evenly distributed along the X chromosome as had been previously postulated. A distal duplication covering 35% of the X chromosome promotes female differentiation, a much larger proximal duplication of 60% results in male differentiation. The strong feminizing effect of distal duplications originates from a small segment that, when present in two doses, activates Sxl, a key gene for sex determination and dosage compensation. Our results suggest that Sxl can be activated to intermediate levels. Steinmann-Zwicky M M Nöthiger R R eng Journal Article

UNITED STATES Cell 0413066 IM Aneuploidy Animal Drosophila melanogaster anatomy & histology genetics Female Genes Genes, Lethal Genotype Larva cytology Male Salivary Glands cytology Sex Determination (Analysis) Support, Non-U.S. Gov't X Chromosome FBrf0108422 99203437 10101121 1999 06 22 1999 06 22 2001 11 02

0950-1991 126 9 1999 May Identification of mutations that cause cell migration defects in mosaic clones. 1869-78 Cell movement is an important feature of animal development, wound healing and tumor metastasis; however, the mechanisms underlying cell motility remain to be elucidated. To further our understanding, it would be useful to identify all of the proteins that are essential for a cell to migrate, yet such information is not currently available for any cell type. We have carried out a screen for mutations affecting border cell migration in Drosophila. Mutations that cause defects in mosaic clones were identified, so that genes that are also required for viability could be detected. From 6000 mutagenized lines, 20 mutations on chromosome 2R were isolated that cause defects in border cell position. One of the mutations was dominant while all of the recessive mutations appeared to be homozygous lethal. This lethality was used to place the mutations into 16 complementation groups. Many of the mutations failed to complement cytologically characterized deficiencies, allowing their rapid mapping. Mutations in three loci altered expression of a marker gene in the border cells, whereas the remaining mutations did not. One mutation, which caused production of supernumerary border cells, was found to disrupt the costal-2 locus, indicating a role for Hedgehog signaling in border cell development. This screen identified many new loci required for border cell migration and our results suggest that this is a useful approach for elucidating the mechanisms involved in cell motility. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA. Liu Y Y Montell D J DJ eng GM46425 GM NIGMS Journal Article

ENGLAND Development 8701744 62-50-0 Ethyl Methanesulfonate EC 3.2.1.23 beta-Galactosidase IM Animal Animals, Genetically Modified Cell Movement genetics Cell Nucleus physiology ultrastructure Clone Cells Crosses, Genetic Drosophila melanogaster embryology genetics Embryo, Nonmammalian cytology physiology Ethyl Methanesulfonate Female Genetic Complementation Test Male Mosaicism Mutagenesis Oocytes cytology physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. beta-Galactosidase biosynthesis genetics FBrf0104760 98429525 9755202 1998 11 16 1998 11 16 2001 11 02

0016-6731 150 2 1998 Oct LUSH odorant-binding protein mediates chemosensory responses to alcohols in Drosophila melanogaster. 711-21 The molecular mechanisms mediating chemosensory discrimination in insects are unknown. Using the enhancer trapping approach, we identified a new Drosophila mutant, lush, with odorant-specific defects in olfactory behavior. lush mutant flies are abnormally attracted to high concentrations of ethanol, propanol, and butanol but have normal chemosensory responses to other odorants. We show that wild-type flies have an active olfactory avoidance mechanism to prevent attraction to concentrated alcohol, and this response is defective in lush mutants. This suggests that the defective olfactory behavior associated with the lush mutation may result from a specific defect in chemoavoidance. lush mutants have a 3-kb deletion that produces a null allele of a new member of the invertebrate odorant-binding protein family, LUSH. LUSH is normally expressed exclusively in a subset of trichoid chemosensory sensilla located on the ventral-lateral surface of the third antennal segment. LUSH is secreted from nonneuronal support cells into the sensillum lymph that bathes the olfactory neurons within these sensilla. Reintroduction of a cloned wild-type copy of lush into the mutant background completely restores wild-type olfactory behavior, demonstrating that this odorant-binding protein is required in a subset of sensilla for normal chemosensory behavior to a subset of odorants. These findings provide direct evidence that odorant-binding proteins are required for normal chemosensory behavior in Drosophila and may partially determine the chemical specificity of olfactory neurons in vivo. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9111, USA. Kim M S MS Repp A A Smith D P DP eng GENBANK AF001621 DC-02539-2 DC NIDCD Journal Article

UNITED STATES Genetics 0374636 0 Alcohols 0 DNA Transposable Elements 0 Receptors, Odorant 0 Recombinant Fusion Proteins 0 odorant-binding protein IM Alcohols Amino Acid Sequence Animal Animals, Genetically Modified Behavior, Animal Cloning, Molecular DNA Transposable Elements genetics Drosophila genetics physiology Female Genes, Structural, Insect genetics Male Molecular Sequence Data Mutation Odors Receptors, Odorant analysis genetics Recombinant Fusion Proteins Restriction Mapping Sense Organs chemistry Sequence Analysis, DNA Smell genetics Support, U.S. Gov't, P.H.S. FBrf0128401 20349377 10889058 2000 10 04 2000 10 04 2000 12 18

0959-437X 10 4 2000 Aug Drawing lines in the Drosophila wing: initiation of wing vein development. 393-8 It has been proposed that wing veins in Drosophila form at boundaries between discrete sectors of cells that subdivide the anterior-posterior axis of the developing wing primordium. Recently, analysis of events underlying initiation of vein formation suggests that there is a general developmental mechanism for drawing lines between adjacent domains of cells, which is referred to as 'for-export-only-signaling'. In this model, cells in one domain produce a short range signal to which they cannot respond. As a consequence of this constraint, cells lying in a narrow line immediately outside the signal-producing domain are the only cells that can respond to the signal by activating expression of vein-promoting genes. Division of Biology, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla 92093-0349, USA. bier@biomail.ucsd.edu Bier E E eng Journal Article Review Review, Tutorial

ENGLAND Curr Opin Genet Dev 9111375 IM Animal Drosophila melanogaster genetics growth & development Evolution Wing growth & development 45 FBrf0087267 96188856 8614625 1996 06 06 1996 06 06 2000 12 18

0305-1048 24 7 1996 Apr 1 Drosophila immunity: a comparative analysis of the Rel proteins dorsal and Dif in the induction of the genes encoding diptericin and cecropin. 1238-45 In Drosophila, bacterial challenge induces the rapid transcription of several genes encoding potent antibacterial peptides. The upstream sequences of the diptericin and cecropin Al genes, which have been investigated in detail, contain two, respectively one sequence element homologous to the binding site of the mammalian nuclear factor kappaB. These elements have been shown to be mandatory for immune-induced transcription of both genes. Functional studies have shown that these kappaB-related elements can be the target for the Drosophila Rel proteins dorsal and Dif. Here we present a comparative analysis of the transactivating capacities of these proteins on reporter genes fused to either the diptericin or the cecropin kappaB-related motifs. We conclude from our results: (i) the kappaB motifs of the diptericin and cecropin genes are not functionally equivalent; (ii) the dorsal and Dif proteins have distinct DNA-binding characteristics; (iii) dorsal and Dif can heterodimerize in vitro; (iv) mutants containing no copies of dorsal and a single copy of Dif retain their full capacity to express the diptericin and cecropin genes in response to challenge. Institut de Biologie Moléculaire et Cellulaire, CNRS, Strasbourg, France. Gross I I Georgel P P Kappler C C Reichhart J M JM Hoffmann J A JA eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 DNA Primers 0 DNA-Binding Proteins 0 Dif protein 0 Insect Hormones 0 NF-kappa B 0 Nuclear Proteins 0 Peptides 0 Phosphoproteins 0 diptericin A 0 dorsal protein, Drosophila 80451-04-3 cecropin A IM Animal Base Sequence DNA Primers chemistry DNA-Binding Proteins metabolism physiology Drosophila melanogaster genetics immunology Gene Expression Regulation Insect Hormones genetics Molecular Sequence Data NF-kappa B metabolism Nuclear Proteins physiology Peptides genetics Phosphoproteins physiology Trans-Activation (Genetics) Transcription, Genetic FBrf0102843 98250684 9584097 1998 07 07 1998 07 07 2003 04 25

0016-6731 149 1 1998 May Identification of chromosomal regions involved in decapentaplegic function in Drosophila. 203-15 Signaling molecules of the transforming growth factor beta (TGF-beta) family contribute to numerous developmental processes in a variety of organisms. However, our understanding of the mechanisms which regulate the activity of and mediate the response to TGF-beta family members remains incomplete. The product of the Drosophila decapentaplegic (dpp) locus is a well-characterized member of this family. We have taken a genetic approach to identify factors required for TGF-beta function in Drosophila by testing for genetic interactions between mutant alleles of dpp and a collection of chromosomal deficiencies. Our survey identified two deficiencies that act as maternal enhancers of recessive embryonic lethal alleles of dpp. The enhanced individuals die with weakly ventralized phenotypes. These phenotypes are consistent with a mechanism whereby the deficiencies deplete two maternally provided factors required for dpp's role in embryonic dorsal-ventral pattern formation. One of these deficiencies also appears to delete a factor required for dpp function in wing vein formation. These deficiencies remove material from the 54F-55A and 66B-66C polytene chromosomal regions, respectively. As neither of these regions has been previously implicated in dpp function, we propose that each of the deficiencies removes a novel factor or factors required for dpp function. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Nicholls R E RE Gelbart W M WM eng Journal Article

UNITED STATES Genetics 0374636 0 Bacterial Proteins 0 DNA-Binding Proteins 0 Insect Proteins 0 MAD protein, Drosophila 0 Med protein, Bacillus subtilis 0 Transforming Growth Factor beta 0 dpp protein, Drosophila 144714-21-6 tld protein, Drosophila IM Alleles Animal Bacterial Proteins genetics Chromosome Mapping DNA-Binding Proteins genetics Drosophila melanogaster Insect Proteins genetics physiology Sequence Deletion Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transforming Growth Factor beta genetics FBrf0057902 93272336 8500182 1993 06 30 1993 06 30 2000 12 18

0092-8674 73 5 1993 Jun 4 Spatially localized rhomboid is required for establishment of the dorsal-ventral axis in Drosophila oogenesis. 953-65 The establishment of dorsal-ventral asymmetry of the Drosophila embryo requires a group of genes that act maternally. None of the previously identified dorsal-ventral axis genes are known to produce asymmetrically localized gene products during oogenesis. We show that rhomboid (rho), a novel member of this group, encodes a protein that is localized on the apical surface of the dorsal-anterior follicle cells surrounding the oocyte. Loss of rho function causes ventralization of the eggshell and the embryo, whereas ectopic expression leads to dorsalization of both structures. Thus, spatially restricted rho is necessary and sufficient for dorsal-ventral axis formation. We propose, based on these observations and double mutant experiments, that the spatially restricted rho protein leads to selective activation of the epidermal growth factor receptor in the dorsal follicle cells and subsequently the specification of the dorsal follicle cells. Howard Hughes Medical Institute, University of California, San Francisco 94143-0724. Ruohola-Baker H H Grell E E Chou T B TB Baker D D Jan L Y LY Jan Y N YN eng Journal Article

UNITED STATES Cell 0413066 0 Egg Proteins 0 RNA, Antisense IM Egfr Toll grk rho Animal Cell Polarity Drosophila melanogaster embryology genetics Egg Proteins biosynthesis Gene Expression Oogenesis genetics RNA, Antisense biosynthesis Support, Non-U.S. Gov't FBrf0058920 93375306 8366341 1993 10 05 1993 10 05 2000 12 18

0270-6474 13 9 1993 Sep Insulin-like receptor and insulin-like peptide are localized at neuromuscular junctions in Drosophila. 3692-704 Insulin and insulin-like growth factor (IGF) receptors are members of the tyrosine kinase family of receptors, and are thought to play an important role in the development and differentiation of neurons. Here we report the presence of an insulin-like peptide and an insulin receptor (dInsR) at the body wall neuromuscular junction of developing Drosophila larvae. dInsR-like immunoreactivity was found in all body wall muscles at the motor nerve branching regions, where it surrounded synaptic boutons. The identity of this immunoreactivity as a dInsR was confirmed by two additional schemes, in vivo binding of labeled insulin and immunolocalization of phosphotyrosine. Both methods produced staining patterns markedly similar to dInsR-like immunoreactivity. The presence of a dInsR in whole larvae was also shown by receptor binding assays. This receptor was more specific for insulin (> 25-fold) than for IGF II, and did not appear to bind IGF I. Among the 30 muscle fibers per hemisegment, insulin-like immunoreactivity was found only on one fiber, and was localized to a subset of morphologically distinct synaptic boutons. Staining in the CNS was limited to several cell bodies in the brain lobes and in a segmental pattern throughout most of the abdominal ganglia, as well as in varicosities along the neuropil areas of the ventral ganglion and brain lobes. Insulin-like peptide and dInsR were first detected by early larval development, well after neuromuscular transmission begins. The developmental significance of an insulin-like peptide and its receptor at the neuromuscular junction is discussed. Department of Biology, University of Massachusetts, Amherst 01003. Gorczyca M M Augart C C Budnik V V eng NS30072-01 NS NINDS Journal Article

UNITED STATES J Neurosci 8102140 11061-68-0 Insulin EC 2.7.1.112 Receptor, Insulin IM Animal Drosophila melanogaster growth & development metabolism Female Immunohistochemistry Insulin analysis metabolism Larva Muscles cytology metabolism Nervous System cytology metabolism Neuromuscular Junction metabolism Oviposition Receptor, Insulin analysis metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0059074 93204909 8455566 1993 04 16 1993 04 16 2002 09 23

0026-8925 237 1-2 1993 Feb Cis-regulatory sequences leading to female-specific expression of yolk protein genes 1 and 2 in the fat body of Drosophila melanogaster. 41-8 The three yolk protein genes (yp) of Drosophila melanogaster are transcribed in a sex- and tissue-limited fashion. We have searched for cis-regulatory sequences in regions flanking yp1 and yp2 to identify the elements that confer female-specific expression in the fat body. One such 127 bp element has previously been identified in this region. We show here the existence of two additional regions which confer female fat body-specific expression on an Adh reporter gene and on the native yp2 gene, respectively. This suggests some redundancy in the regulation of expression of the yp genes. Computer searches for putative binding sites for the DSX protein, which regulates sex-specific expression of the yp genes, revealed several such sites in our constructs. However, the significance of these is unclear since many such sites also occur in genes which one would not expect to be regulated in a sex-specific manner (e.g. Adh, Actin 5C). We suggest that DSX acts in concert with other proteins to mediate sex- and tissue-specific expression of the yp genes. Developmental Biology Center, University of Edinburgh, Scotland. Abrahamsen N N Martinez A A Kjaer T T Søndergaard L L Bownes M M eng Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA-Binding Proteins 0 Egg Proteins 0 Insect Hormones 0 Recombinant Proteins 0 doublesex protein, Drosophila EC 1.1.1.1 Alcohol Dehydrogenase IM adh yp1 yp2 Alcohol Dehydrogenase genetics Animal Base Sequence DNA-Binding Proteins genetics Drosophila melanogaster genetics Egg Proteins biosynthesis genetics Enhancer Elements (Genetics) genetics Fat Body metabolism Female Insect Hormones genetics Molecular Sequence Data Promoter Regions (Genetics) genetics Recombinant Proteins Regulatory Sequences, Nucleic Acid genetics Repetitive Sequences, Nucleic Acid genetics Sequence Deletion Sex Characteristics Support, Non-U.S. Gov't Tissue Distribution FBrf0102482 98273627 9613571 1998 06 18 1998 06 18 2003 06 16

0026-8925 258 1-2 1998 Apr Genomic organization of the segment polarity gene pan in Drosophila melanogaster. 45-52 We previously described the molecular cloning of a mammalian T cell factor 1 (TCF-1)-like protein from Drosophila melanogaster, encoded by the pangolin (pan) locus, and demonstrated that it consists of a DNA binding domain similar to that of other high mobility group proteins and a protein-protein interaction domain that binds beta-catenin (Armadillo in Drosophila) but that it lacks a transcriptional activation domain. Here we show that the pan locus spans approximately 50 kb and the mRNA results from the splicing of 13 exons. We note remarkable conservation of the exon/intron boundaries between the human and D. melanogaster genes, suggesting that they share a common ancestor. Chromosomal in situ hybridization locates pan to the base of chromosome 4, near the cubitus interruptus locus. Restriction map and sequence analyses confirm their close proximity. The small fourth chromosome undergoes little or no recombination and was previously reported to lack DNA polymorphisms; however, we note two DNA polymorphisms occurring in three combinations within the pan locus, demonstrating the presence of synonymous substitutions and the past occurrence of recombination. We present evidence suggesting that the protein encoded by pan is more similar to mammalian TCF-1 and Caenorhabditis elegans POP-1 than to mammalian LEF-1. Department of Immunology, University Hospital, Utrecht, The Netherlands. Dooijes D D van Beest M M van de Wetering M M Boulanger G G Jones T T Clevers H H Mortin M A MA eng Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA-Binding Proteins 0 Insect Proteins 0 Transcription Factors 138415-19-7 LEF-1 protein IM Amino Acid Sequence Animal Chromosome Mapping Cloning, Molecular DNA-Binding Proteins chemistry Drosophila melanogaster genetics Genes, Insect In Situ Hybridization Insect Proteins genetics Molecular Sequence Data Polymorphism (Genetics) Restriction Mapping Support, Non-U.S. Gov't Transcription Factors chemistry genetics FBrf0102347 98213682 9545464 1998 05 29 1998 05 29 2000 12 18

0022-2844 46 5 1998 May Patterns of base composition within the genes of Drosophila melanogaster. 534-41 Base composition is not uniform across the genome of Drosophila melanogaster. Earlier analyses have suggested that there is variation in composition in D. melanogaster on both a large scale and a much smaller, within-gene, scale. Here we present analyses on 117 genes which have reliable intron/exon boundaries and no known alternative splicing. We detect significant heterogeneity in G+C content among intron segments from the same gene, as well as a significant positive correlation between the intron and the third codon position G+C content within genes. Both of these observations appear to be due, in part, to an overall decline in intron and third codon position G+C content along Drosophila genes with introns. However, there is also evidence of an increase in third codon position G+C content at the start of genes; this is particularly evident in genes without introns. This is consistent with selection acting against preferred codons at the start of genes. Department of Biology, Radford University, Radford, VA 24142, USA. rklimanrunet.edu Kliman R M RM Eyre-Walker A A eng Journal Article

UNITED STATES J Mol Evol 0360051 IM Animal Base Composition Drosophila melanogaster genetics Exons Genes, Insect Introns Support, Non-U.S. Gov't Variation (Genetics) FBrf0093373 97321290 9178011 1997 08 12 1997 08 12 2001 11 02

0016-6731 146 2 1997 Jun Ras1-mediated modulation of Drosophila homeotic function in cell and segment identity. 619-28 Mutations of the Drosophila homeotic proboscipedia gene (pb, the Hox-A2/B2 homologue) provoke dose-sensitive defects. These were used to search for dose-sensitive dominant modifiers of pb function. Two identified interacting genes were the proto-oncogene Ras1 and its functional antagonist Gap1, prominent intermediaries in known signal transduction pathways. Ras1+ is a positive modifier of pb activity both in normal and ectopic cell contexts, while the Ras1-antagonist Gap1 has an opposite effect. A general role for Ras1 in homeotic function is likely, since Ras1+ activity also modulates functions of the homeotic loci Sex combs reduced and Ultrabithorax. Our data suggest that the modulation occurs by a mechanism independent of transcriptional control of the homeotic loci themselves, or of the Ras1/Gap1 genes. Taken together our data support a role for Ras1-mediated cell signaling in the homeotic control of segmental differentiation. CBD-CNRS, Toulouse, France. Boube M M Benassayag C C Seroude L L Cribbs D L DL eng Journal Article

UNITED STATES Genetics 0374636 0 GTPase-Activating Proteins 0 Proteins 0 ras GTPase-Activating Proteins EC 3.6.1.- ras Proteins IM Animal Animals, Genetically Modified Body Patterning Drosophila melanogaster anatomy & histology genetics growth & development GTPase-Activating Proteins Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Genes, ras In Situ Hybridization Mutation Phenotype Proteins genetics metabolism Signal Transduction Support, Non-U.S. Gov't Transcription, Genetic ras GTPase-Activating Proteins ras Proteins metabolism FBrf0088595 96242086 8656284 1996 07 30 1996 07 30 2002 11 01

0270-6474 16 12 1996 Jun 15 Characterization of Drosophila tyramine beta-hydroxylase gene and isolation of mutant flies lacking octopamine. 3900-11 Octopamine is likely to be an important neuroactive molecule in invertebrates. Here we report the molecular cloning of the Drosophila melanogaster gene, which encodes tyramine beta-hydroxylase (TBH), the enzyme that catalyzes the last step in octopamine biosynthesis. The deduced amino acid sequence of the encoded protein exhibits 39% identity to the evolutionarily related mammalian dopamine beta-hydroxylase enzyme. We generated a polyclonal antibody against the protein product of T beta h gene, and we demonstrate that the TBH expression pattern is remarkably similar to the previously described octopamine immunoreactivity in Drosophila. We further report the creation of null mutations at the T beta h locus, which result in complete absence of TBH protein and blockage of the octopamine biosynthesis. T beta h-null flies are octopamine-less but survive to adulthood. They are normal in external morphology, but the females are sterile, because although they mate, they retain fully developed eggs. Finally, we demonstrate that this defect in egg laying is associated with the octopamine deficit, because females that have retained eggs initiate egg laying when transferred onto octopamine-supplemented food. Biology Department, Brandeis University, Waltham, Massachusetts 02254, USA. Monastirioti M M Linn C E CE Jr White K K eng GENBANK Z70316 NS23510 NS NINDS RR05615 RR NCRR Journal Article

UNITED STATES J Neurosci 8102140 104-14-3 Octopamine 51-67-2 Tyramine EC 1.- Mixed Function Oxygenases EC 1.14.- tyramine beta-hydroxylase EC 1.14.17.1 Dopamine beta-Hydroxylase IM Animal Antibody Specificity Base Sequence Blotting, Northern Cloning, Molecular Dopamine beta-Hydroxylase genetics Drosophila melanogaster genetics Female In Situ Hybridization Mixed Function Oxygenases genetics immunology Molecular Sequence Data Mutation physiology Octopamine deficiency immunology pharmacology Oocytes physiology Reproduction physiology Sequence Analysis, DNA Sequence Homology, Amino Acid Sex Behavior, Animal physiology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Tyramine metabolism FBrf0103402 98358782 9693879 1998 08 31 1998 08 31 2000 12 18

0011-4529 92 369 1997 Heat shock gene expression during recovery after transient cold shock in Drosophila auraria (Diptera: Drosophilidae). 91-8 Newly synthesized polypeptides during recovery from prolonged cold treatment (0 degree to -1 degree C) of Drosophila auraria, a montium subgroup species, of the melanogaster species group, were analysed in denaturing polyacrylamide gels. In addition, during the cold shock recovery period, Northern analysis of the hsp83 mRNA was performed. A significant induction of two polypeptides, which exhibited electrophoretic mobilities, with the heat inducible 83 and 70 kD hsp83 and hsp70 was detected, but no such induction was evident in the so-called 'small' hsp genes. These results are compared and discussed with those observed in D. melanogaster. Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Science, Aristotle University of Thessaloniki (AUTH), Greece. Yiangou M M Tsapogas P P Nikolaidis N N Scouras Z G ZG eng Journal Article

ENGLAND Cytobios 0207227 0 Heat-Shock Proteins 0 Heat-Shock Proteins 70 0 Protozoan Proteins 0 RNA, Messenger 0 heat-shock protein 83 IM Animal Cold Drosophila genetics Drosophila melanogaster genetics Gene Expression Regulation physiology Heat-Shock Proteins biosynthesis genetics Heat-Shock Proteins 70 biosynthesis genetics Heat-Shock Response genetics Larva Protozoan Proteins biosynthesis genetics RNA, Messenger biosynthesis Salivary Glands metabolism FBrf0130298 20394308 10934486 2000 10 19 2000 10 19 2001 06 23

1465-7392 2 8 2000 Aug Multi-layered regulation of courtship behaviour. E145-6 The fruitless gene governs courtship in male, but not female, Drosophila, yet it is expressed and specifically spliced in the brains of both sexes. New experiments reveal that a splice-recognition site retained in the mature message in females provides the basis for sex-specific translational repression. Wasserman S A SA eng Comment News

ENGLAND Nat Cell Biol 100890575 0 Nerve Tissue Proteins 0 Nuclear Proteins 0 Ribonucleoproteins 0 Transcription Factors 0 fruitless protein 0 transformer protein, Drosophila 0 transformer-2 protein IM Nat Cell Biol. 2000 Aug;2(8):500-6 10934470 Alternative Splicing genetics Animal Courtship Drosophila melanogaster genetics Female Male Muscles metabolism Mutation Nerve Tissue Proteins biosynthesis genetics Nuclear Proteins metabolism Open Reading Frames genetics Regulatory Sequences, Nucleic Acid genetics Ribonucleoproteins metabolism Sex Characteristics Transcription Factors biosynthesis genetics Translation, Genetic genetics FBrf0141654 21617600 11741549 2001 12 19 2002 01 22 2002 11 08

1097-2765 8 5 2001 Nov Replacement of Fab-7 by the gypsy or scs insulator disrupts long-distance regulatory interactions in the Abd-B gene of the bithorax complex. 1145-51 Chromatin domain boundaries, like scs or gypsy insulators in Drosophila, have been identified in transgene assays through their enhancer-blocking activity. Boundary elements in the bithorax complex (BX-C), such as Fab-7 and Fab-8, have been identified genetically and been shown to have insulator activity in transgene assays. However, it is not clear whether boundary elements identified in transgene assays will function appropriately in chromosomal contexts such as BX-C. Using gene conversion, we have substituted the scs or gypsy insulators for Fab-7. We find that both scs and gypsy are very potent insulators in the ectoderm, but surprisingly, the insulating activity of gypsy (but not scs) is lost in the CNS. Our results reveal that the Fab-7 boundary must have special properties that scs and gypsy lack, which allow it to function appropriately in BX-C regulation. Department of Zoology and Animal Biology, University of Geneva, 1211 4, Geneva, Switzerland. Hogga I I Mihaly J J Barges S S Karch F F eng Journal Article

United States Mol Cell 9802571 0 Abd-B proteins, Drosophila 0 Drosophila Proteins 0 Homeodomain Proteins IM Abdomen Animal Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics physiology Gene Conversion Genes, Insect Homeodomain Proteins genetics Male Regulatory Sequences, Nucleic Acid Support, Non-U.S. Gov't FBrf0042626 85102726 3917963 1985 03 11 1985 03 11 2000 12 18

0016-6731 109 1 1985 Jan Shortvein, a new component of the decapentaplegic gene complex in Drosophila melanogaster. 119-43 Our laboratory has been concerned with the structure and function of the decapentaplegic gene complex (DPP-C) in Drosophila melanogaster. To define the boundaries of the complex, we have studied the genetics of mutations allelic to a previously discovered mutation shortvein (shv), known to reside near decapentaplegic. We found that shortvein resides distal to Hin-d and dpp within the same polytene chromosome doublet, 22F1-2. Lesions in shv can affect not only the formation of the wing veins but also can interfere with normal development of parts of the adult and/or be lethal. Like those of dpp mutants, the shv-associated adult abnormalities affect distal epidermal structures. Some shv lesions cause a larval lethal syndrome which is associated with an unusually long larval stage (ca. five to six times its normal duration). Lesions in shv exhibit an involved pattern of complementation with dpp mutations, indicating that both shv and dpp are parts of a single gene complex. A subset of the array of mutant phenotypes displayed by shv/dpp trans-heterozygotes appear to be dpp-specific phenotypes; we interpret these as reflecting an inactivation effect of certain shv alleles on dpp functions. The other abnormalities displayed by these trans-heterozygotes appear to be shv-specific defects; we view these as indicating an inactivation effect of certain dpp mutations on shv functions. Furthermore, embryonic lethal (EL) mutations within the DPP-C exhibit allelic interactions with all shv mutations. We conclude that the shortvein region represents a newly identified integrated portion of the DPP-C. Segal D D Gelbart W M WM eng CA-00588 CA NCI GM-28669 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Drosophila melanogaster genetics ultrastructure Genes, Lethal Larva Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Wing ultrastructure FBrf0158858 22523837 12636917 2003 03 14 2003 04 18

1534-5807 4 3 2003 Mar Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye. 359-69 Receptor tyrosine kinases such as the EGF receptor transduce extracellular signals into multiple cellular responses. In the developing Drosophila eye, EGFR activity triggers cell differentiation. Here we focus on three additional cell autonomous aspects of EGFR function and their coordination with differentiation, namely, withdrawal from the cell cycle, mitosis, and cell survival. We find that, whereas differentiation requires intense signaling, dependent on multiple reinforcing ligands, lesser EGFR activity maintains cell cycle arrest, promotes mitosis, and protects against cell death. Each response requires the same Ras, Raf, MAPK, and Pnt signal transduction pathway. Mitotic and survival responses also involve Pnt-independent branches, perhaps explaining how survival and mitosis can occur independently. Our results suggest that, rather than triggering all or none responses, EGFR coordinates partially independent processes as the eye differentiates. Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Yang Lihui L Baker Nicholas E NE eng GM47892 GM NIGMS Journal Article

United States Dev Cell 101120028 0 Drosophila Proteins 0 Growth Substances 0 MAP Kinase Signaling System 0 Proto-Oncogene Proteins 0 keren protein, Drosophila 0 pointed protein EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 3.6.1.- ras Proteins IM Animal Cell Cycle physiology Cell Death genetics Cell Differentiation physiology Cell Lineage genetics Cell Survival physiology Drosophila Proteins genetics metabolism Drosophila melanogaster cytology embryology metabolism Eye cytology embryology metabolism Female G1 Phase genetics G2 Phase genetics Gene Expression Regulation, Developmental genetics Growth Substances genetics metabolism MAP Kinase Signaling System genetics Male Mitogen-Activated Protein Kinases genetics metabolism Proto-Oncogene Proteins genetics metabolism Proto-Oncogene Proteins c-raf genetics metabolism Receptor, Epidermal Growth Factor genetics metabolism Signal Transduction genetics Support, U.S. Gov't, P.H.S. Up-Regulation genetics ras Proteins genetics metabolism FBrf0160414 22704212 12818167 2003 06 23 2003 08 15

0896-6273 38 6 2003 Jun 19 From fragile X mental retardation protein to Rac1 GTPase: new insights from Fly CYFIP. 843-5 Mutations in either the Rho GTPase pathway or in the fragile X mental retardation (FMR1) gene produce neuronal connectivity defects. In this issue of Neuron, Schenck et al. use biochemical and genetic approaches in Drosophila to examine the interactions between dFMR1 and dRac1 and provide evidence that the cytoplasmic FMRP interacting protein (CYFIP) links Rac-dependent cytoskeleton remodeling and dFMR1-dependent control of translation in a unique pathway to modulate neuronal morphogenesis. Institut Cochin, INSERM unité 567, CNRS 8104, Université Paris V, CHU Cochin, 24 Rue du Faubourg Saint Jacques, 75014, Paris, France. Billuart Pierre P Chelly Jamel J eng Comment Journal Article

United States Neuron 8809320 0 Carrier Proteins 0 Drac1 protein 0 FMR1 protein, Drosophila 0 Nerve Tissue Proteins 0 RNA-Binding Proteins 0 p140Sra-1 protein 139135-51-6 FMR-1 protein EC 3.6.1.- rac GTP-Binding Proteins EC 3.6.1.- rac1 GTP-Binding Protein IM Neuron. 2003 Jun 19;38(6):887-98 12818175 Animal Carrier Proteins genetics physiology Drosophila melanogaster genetics Human Mental Retardation genetics Mutation Nerve Tissue Proteins genetics Neurons ultrastructure RNA-Binding Proteins genetics physiology rac GTP-Binding Proteins genetics physiology rac1 GTP-Binding Protein FBrf0158985 22505399 12618403 2003 03 05

0016-6731 163 2 2003 Feb piggyBac-Based Insertional Mutagenesis and Enhancer Detection as a Tool for Functional Insect Genomics. 647-61 Transposon mutagenesis provides a fundamental tool for functional genomics. Here we present a non-species-specific, combined enhancer detection and binary expression system based on the transposable element piggyBac: For the different components of this insertional mutagenesis system, we used widely applicable transposons and distinguishable broad-range transformation markers, which should enable this system to be operational in nonmodel arthropods. In a pilot screen in Drosophila melanogaster, piggyBac mutator elements on the X chromosome were mobilized in males by a Hermes-based jumpstarter element providing piggyBac transposase activity under control of the alpha1-tubulin promoter. As primary reporters in the piggyBac mutator elements, we employed the heterologous transactivators GAL4Delta or tTA. To identify larval and adult enhancer detectors, strains carrying UASp-EYFP or TRE-EYFP as secondary reporter elements were used. Tissue-specific enhancer activities were readily observed in the GAL4Delta/UASp-based systems, but only rarely in the tTA/TRE system. Novel autosomal insertions were recovered with an average jumping rate of 80%. Of these novel insertions, 3.8% showed homozygous lethality, which was reversible by piggyBac excision. Insertions were found in both coding and noncoding regions of characterized genes and also in noncharacterized and non-P-targeted CG-number genes. This indicates that piggyBac will greatly facilitate the intended saturation mutagenesis in Drosophila. Lehrstuhl für Genetik, Universität Bayreuth, 95447 Bayreuth, Germany. Horn Carsten C Offen Nils N Nystedt Sverker S Häcker Udo U Wimmer Ernst A EA eng Journal Article

United States Genetics 0374636 IM FBrf0091030 97132602 8978054 1997 03 31 1997 03 31 2000 12 18

0016-6731 144 4 1996 Dec The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. 1673-9 The production of female germline chimeras is invaluable for analyzing the tissue specificity of recessive female sterile mutations as well as detecting the maternal effect of recessive zygotic lethal mutations. Previously, we developed the "FLP-DFS" technique to efficiently generate germline clones. This technique uses the X-linked germline-dependent dominant female sterile mutation ovoD1 as a selection for the detection of germline recombination events, and the FLP-FRT recombination system to promote site-specific chromosomal exchange. This method allows the efficient production of germline mosaics only on the X chromosome. In this paper we have built chromosomes that allow the use of this technique to the autosomes. We describe the various steps involved in the development of this technique as well as the properties of the chromosomes utilized. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. Chou T B TB Perrimon N N eng Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Drosophila melanogaster genetics Female Genes, Dominant Genes, Insect Genetic Techniques Germ-Line Mutation Male Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. FBrf0139757 21403261 11511363 2001 08 20 2001 09 13 2003 02 03

1097-2765 8 1 2001 Jul Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. 95-104 The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional alpha helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins. Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA. Wu J W JW Cocina A E AE Chai J J Hay B A BA Shi Y Y eng CA90269 CA NCI Journal Article

United States Mol Cell 9802571 0 Insect Proteins 0 Neuropeptides 0 Peptide Fragments 0 grim protein, Drosophila 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila IM Amino Acid Sequence Animal Apoptosis physiology Calorimetry Crystallography, X-Ray Drosophila melanogaster physiology Insect Proteins chemistry genetics metabolism Kinetics Models, Molecular Molecular Sequence Data Neuropeptides genetics metabolism Peptide Fragments chemistry genetics metabolism Protein Binding Protein Conformation Protein Structure, Tertiary Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0135947 21189484 11292875 2001 04 09 2001 06 07

0036-8075 292 5514 2001 Apr 6 A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. 107-10 The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue. Brown University, Providence, RI 02912, USA., University of Massachusetts, Amherst, MA 01003, USA. Marc_Tatar@Brown.edu Tatar M M Kopelman A A Epstein D D Tu M P MP Yin C M CM Garofalo R S RS eng R01 AG16632 AG NIA Journal Article

United States Science 0404511 0 Carrier Proteins 0 INR protein 0 Juvenile Hormones 0 Triglycerides 11061-68-0 Insulin 40596-69-8 Methoprene EC 1.15.1.1 Superoxide Dismutase EC 2.7.1.112 Protein-Tyrosine Kinase EC 2.7.1.112 Receptor, Insulin IM Science. 2001 Apr 6;292(5514):41-3 11294208 Aging physiology Alleles Animal Carrier Proteins genetics physiology Corpora Allata metabolism Drosophila melanogaster genetics physiology Female Fertility Genes, Insect Genotype Insulin pharmacology Juvenile Hormones metabolism Longevity physiology Male Methoprene pharmacology Mutation Protein-Tyrosine Kinase genetics physiology Receptor, Insulin genetics physiology Reproduction Signal Transduction Superoxide Dismutase metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Triglycerides metabolism Vitellogenesis drug effects FBrf0160371 22640875 12756183 2003 05 20 2003 09 10

0950-1991 130 13 2003 Jul pannier and pointedP2 act sequentially to regulate Drosophila heart development. 3015-26 The Drosophila heart consists of two major cell types: cardioblasts, which form the contractile tube of the heart; and pericardial cells, which flank the cardioblasts and are thought to filter and detoxify the blood or hemolymph of the fly. We present the completion of the entire cell lineage of all heart cells. Notably, we detect a previously unappreciated distinction between the lineages of heart cells located in the posterior seven segments relative to those located more anteriorly. Using a genetic screen, we have identified the ETS-transcription factor pointed as a key regulator of cardioblast and pericardial cell fates in the posterior seven segments of the heart. In this domain, pointed promotes pericardial cell development and opposes cardioblast development. We find that this function of pointed is carried out primarily if not exclusively by the pointedP2 isoform and, that in this context, pointedP2 may act independently of Ras/MAPK pathway activity. We go on to show that the GATA transcription factor pannier acts early in dorsal mesoderm development to promote the development of the cardiac mesoderm and thus all heart cells. Finally, we demonstrate that pannier acts upstream of pointed in a developmental pathway in which pannier promotes cardiac mesoderm formation, and pointed acts subsequently in this domain to distinguish between cardioblast and pericardial cell fates. Department of Genetics, Washington University School of Medicine, 4566 Scott Avenue, St Louis, MO 63110, USA. Alvarez Alejandra D AD Shi Weiyang W Wilson Beth A BA Skeath James B JB eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Protein Isoforms 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 Trans-Activators 0 Transcription Factors 0 pannier protein 0 pointed protein 0 tinman protein 108911-13-3 even-skipped protein, Drosophila EC 3.6.1.- ras Proteins IM Animal Cell Differentiation physiology Cell Lineage Drosophila Proteins Drosophila melanogaster anatomy & histology embryology physiology Gene Expression Regulation, Developmental Genes, Insect Heart anatomy & histology growth & development physiology Mesoderm physiology Models, Biological Protein Isoforms genetics metabolism Proto-Oncogene Proteins genetics metabolism RNA Interference Repressor Proteins genetics metabolism Support, U.S. Gov't, Non-P.H.S. Trans-Activators genetics metabolism Transcription Factors genetics metabolism ras Proteins metabolism FBrf0032262 79073133 103000 1979 02 23 1979 02 23 2000 12 18

0028-0836 276 5688 1978 Dec 7 A gene complex controlling segmentation in Drosophila. 565-70 The bithorax gene complex in Drosophila contains a minimum of eight genes that seem to code for substances controlling levels of thoracic and abdominal development. The state of repression of at least four of these genes is controlled by cis-regulatory elements and a separate locus (Polycomb) seems to code for a repressor of the complex. The wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element. Lewis E B EB eng Journal Article

ENGLAND Nature 0410462 IM Abdomen anatomy & histology growth & development Animal Chromosome Mapping Drosophila melanogaster genetics growth & development Genes, Regulator Mutation Support, U.S. Gov't, P.H.S. Thorax anatomy & histology growth & development FBrf0145129 21669005 11810228 2002 01 25 2002 02 19 2003 01 03

1617-4615 266 4 2001 Dec corto genetically interacts with Pc-G and trx-G genes and maintains the anterior boundary of Ultrabithorax expression in Drosophila larvae. 572-83 In Drosophila melanogaster, segment identity is determined by specific expression of homeotic genes (Hox). The Hox expression pattern is first initiated by gap and pair-rule genes and then maintained by genes of the Polycomb-group (Pc-G) and the trithorax-group (trx-G). The corto gene is a putative regulator of the Hox genes since mutants exhibit homeotic transformations. We show here that, in addition to previously reported genetic interactions with the Pc-G genes Enhancer of zeste, Polycomb and polyhomeotic, mutations in corto enhance the extra-sex-comb phenotype of multi sex combs, Polycomb-like and Sex combs on midleg. corto also genetically interacts with a number of trx-G genes (ash1, kismet, kohtalo, moira, osa, Trithorax-like and Vha55). The interactions with genes of the trx-G lead to phenotypes displayed in the wing, in the postpronotum or in the thoracic mechanosensory bristles. In addition, we analyzed the regulation of the Hox gene Ultrabithorax (Ubx) in corto mutants. Our results provide evidence that corto maintains the anterior border of Ubx expression in third-instar larvae. We suggest that this regulation is accomplished through an interaction with the products of the Pc-G and trx-G genes. Equipe Développement et Evolution, Biologie du Développement, UMR 7622 CNRS, Université Pierre et Marie Curie, 9, Quai Saint-Bernard, 75252 Paris Cedex 05, France. Lopez A A Higuet D D Rosset R R Deutsch J J Peronnet F F eng Journal Article 2001 10 16

Germany Mol Genet Genomics 101093320 0 CCF protein, Drosophila 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Insect Proteins 0 trithorax gene product 0 ultrabithorax protein 134549-01-2 Polycomb protein, insect IM Animal Body Patterning genetics DNA-Binding Proteins genetics Drosophila embryology genetics Genes, Homeobox Genes, Insect Homeodomain Proteins genetics Insect Proteins genetics Larva Male Mechanoreceptors abnormalities Mutation Phenotype Support, Non-U.S. Gov't Wing abnormalities FBrf0084258 96026008 7565780 1995 11 21 1995 11 21 2000 12 18

0270-7306 15 11 1995 Nov Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. 6273-82 SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choice. Here we describe the isolation of both dominant and loss-of-function alleles of B52, the gene for a Drosophila SR protein. The allele B52ED was identified as a dominant second-site enhancer of white-apricot (wa), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52ED also exaggerates the mutant phenotype of a distinct white allele carrying a 5' splice site mutation (wDR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so that the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52ED is a recessive lethal allele that fails to complement other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which it was derived revealed a single change in a conserved amino acid in the beta 4 strand of the first RNA-binding domain of B52, which suggests that altered RNA binding is responsible for the dominant phenotype. Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo. Department of Biological Sciences, Columbia University, New York, New York 10027, USA. Peng X X Mount S M SM eng GENBANK X58720 GM37991 GM NIGMS Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA Primers 0 Proteins 0 RNA-Binding Proteins 143295-85-6 B52 protein IM Alleles Amino Acid Sequence Animal Base Sequence DNA Primers chemistry Drosophila melanogaster embryology genetics Frameshift Mutation Genes, Dominant Genes, Structural, Insect Molecular Sequence Data Point Mutation Protein Structure, Tertiary Proteins physiology RNA Splicing RNA-Binding Proteins physiology Sequence Deletion Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0080432 95309674 7789762 1995 07 21 1995 07 21 2000 12 18

0016-6731 139 4 1995 Apr Horka, a dominant mutation of Drosophila, induces nondisjunction and, through paternal effect, chromosome loss and genetic mosaics. 1585-99 Fs(3)Horka (Horka) was described as a dominant female-sterile mutation of Drosophila melanogaster. Genetic and cytological data show that Horka induces mostly equational nondisjunction during spermatogenesis but not chromosome loss and possesses a dominant paternal effect: the X, second, third and the fourth chromosomes, but not the Y, are rendered unstable while undergoing spermatogenesis and may be lost in the descending zygotes. The frequency of Horka-induced chromosome loss is usually 2-4% but varies with the genetic background and can be over 20%. The X chromosome loss occurs during the gonomeric and the initial cleavage divisions. Loss of the X and fourth chromosomes shows no correlation. We propose, based on similarities in the mutant phenotypes with the chromosome destabilizing mutations nonclaret disjunctional and paternal loss, that the normal Horka+ product is required for function of the centromeres and/or nearby regions. Horka is a convenient tool for the generation of gynandromorphs, autosome mosaics and for the study of gene expression in mosaics. Department of Biology, Albert Szent-Györgyi Medical University, Szeged, Hungary. Szabad J J Máthé E E Puro J J eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Deletion Drosophila melanogaster genetics Female Genes, Dominant Genes, Insect Genomic Imprinting Haplotypes Male Mosaicism Mutation Nondisjunction, Genetic Spermatogenesis genetics Support, Non-U.S. Gov't X Chromosome Y Chromosome FBrf0054123 92146936 1783295 1992 03 13 1992 03 13 2000 12 18

0016-6731 129 4 1991 Dec Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology. 1119-36 In mutagenesis screens for recessive female sterile mutations on the second chromosome of Drosophila melanogaster 528 lines were isolated which allow the homozygous females to survive but cause sterility. In 62 of these lines early stages of oogenesis are affected, and these females usually do not lay any eggs. In 333 lines oogenesis proceeds apparently normally to stage 8 of oogenesis, but morphological defects become often apparent during later stages of oogenesis, and are visible in the defective eggs produced by these females whereas 133 lay eggs that appear morphologically normal, but do not support normal embryonic development. Of the lines 341 have been genetically characterized and define a total of 140 loci on the second chromosome. Not all the loci are specific for oogenesis. From the numbers obtained we estimate that the second chromosome of Drosophila contains about 13 loci that are relatively specific for early oogenesis, 70 loci that are specifically required in mid to late oogenesis, and around 30 maternal-effect lethals. Department of Molecular Biology, Princeton University, New Jersey 08544. Schüpbach T T Wieschaus E E eng GM 40558 GM NIGMS HD 15587 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Animal Cell Movement Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics Female Male Mutagenesis Oocytes cytology Oogenesis genetics Ovarian Follicle cytology Ovum cytology Phenotype Reproduction genetics Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0099732 98072338 9409680 1998 01 22 1998 01 22 2003 06 16

0950-1991 124 22 1997 Nov Two signalling pathways specify localised expression of the Broad-Complex in Drosophila eggshell patterning and morphogenesis. 4639-47 The Drosophila eggshell, which has a pair of chorionic appendages (dorsal appendages) located asymmetrically along both the anterior/posterior and dorsal/ventral axes, provides a good model to study signal instructed morphogenesis. We show that the Broad-Complex, a gene encoding zinc-finger transcription factors, is essential for the morphogenesis of dorsal appendages and is expressed in a bilaterally symmetrical pattern in the lateral-dorsal-anterior follicle cells during late oogenesis. This is induced and specified along the dorsoventral axis by an epidermal growth factor receptor signalling pathway, which includes a localised transforming growth factor-alpha like molecule, Gurken, in the oocyte and the Drosophila EGF receptor homologue, Torpedo, in the surrounding somatic follicle cells. Furthermore, the precisely localised expression of BR-C along the AP axis requires a separate signalling pathway, initiated by a transforming growth factor-beta homologue, Decapentaplegic, in nearby follicle cells. These two signalling pathways, one from the oocyte and the other from the follicle cells, co-ordinately specify patches of follicle cells to express the Broad-Complex in a unique position in respect to both major axes, which in turn directs the differentiation of the dorsal appendages in the correct position on the eggshell. Institute of Cell and Molecular Biology, University of Edinburgh, UK. Deng W M WM Bownes M M eng Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 broad-complex protein, Drosophila 0 dpp protein, Drosophila 0 gurken protein, Drosophila 0 pointed protein 76057-06-2 Transforming Growth Factors IM Animal Drosophila melanogaster genetics growth & development metabolism Female Gene Expression Regulation, Developmental Genes, Insect In Situ Hybridization Insect Proteins genetics Male Oocytes growth & development metabolism Proto-Oncogene Proteins genetics Signal Transduction Support, Non-U.S. Gov't Transcription Factors genetics Transforming Growth Factors genetics Zinc Fingers genetics FBrf0056453 92129439 1734025 1992 03 03 1992 03 03 2000 12 18

0021-9525 116 4 1992 Feb Evidence that the stalk of Drosophila kinesin heavy chain is an alpha-helical coiled coil. 957-65 Kinesin is a mechanochemical enzyme composed of three distinct domains: a globular head domain, a rodlike stalk domain, and a small globular tail domain. The stalk domain has sequence features characteristic of alpha-helical coiled coils. To gain insight into the structure of the kinesin stalk, we expressed it from a segment of the Drosophila melanogaster kinesin heavy chain gene and purified it from Escherichia coli. When observed by EM, this protein formed a rodlike structure 40-55 nm long that was occasionally bent at a hingelike region near the middle of the molecule. An additional EM study and a chemical cross-linking study showed that this protein forms a parallel dimer and that the two chains are in register. Finally, using circular dichroism spectroscopy, we showed that this protein is approximately 55-60% alpha-helical in physiological aqueous solution at 25 degrees C, and approximately 85-90% alpha-helical at 4 degrees C. From these results, we conclude that the stalk of kinesin heavy chain forms an alpha-helical coiled coil structure. The temperature dependence of the circular dichroism signal has two major transitions, at 25-30 degrees C and at 45-50 degrees C, which suggests that a portion of the alpha-helical structure in the stalk is less stable than the rest. By producing the amino-terminal (coil 1) and carboxy-terminal (coil 2) halves of the stalk separately in E. coli, we showed that the region that melts below 30 degrees C lies within coil 1, while the majority of coil 2 melts above 45 degrees C. We suggest that this difference in stability may play a role in the force-generating mechanism or regulation of kinesin. Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138. de Cuevas M M Tao T T Goldstein L S LS eng AR21673 AR NIAMS GM35252 GM NIGMS Journal Article

UNITED STATES J Cell Biol 0375356 0 Recombinant Fusion Proteins 69-78-3 Dithionitrobenzoic Acid EC 3.6.1.- Kinesin IM Amino Acid Sequence Animal Circular Dichroism Dithionitrobenzoic Acid Drosophila melanogaster chemistry Kinesin chemistry isolation & purification ultrastructure Microscopy, Electron Molecular Sequence Data Protein Conformation Recombinant Fusion Proteins chemistry isolation & purification ultrastructure Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Temperature FBrf0049889 89276893 2499509 1989 07 21 1989 07 21 2000 12 18

0016-6731 121 2 1989 Feb A cytogenetic analysis of the Punch-tudor region of chromosome 2R in Drosophila melanogaster. 273-80 Eleven chromosomal deficiencies and several rearrangements in the Pu-tud region of chromosome 2R have been generated and examined cytologically. The Pu locus has been localized to chromosome bands 57C5-6 and tud to 57C7-8. Mutagenesis within the region defined by the deletion intervals has resulted in the isolation of 92 new lethal mutations. Seventy-six of these mutations have been separated into 16 complementation groups that have been ordered and placed cytologically by deletion mapping. All new alleles fully complement tud for both lethal and grandchildless phenotypes. The largest number of new mutations, a total of 25, are Pu alleles. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213. O'Donnell J J Boswell R R Reynolds T T Mackay W W eng GM26757 GM NIGMS GM36937 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 EC 3.5.4. Aminohydrolases EC 3.5.4.16 GTP Cyclohydrolase IM Aminohydrolases genetics Animal Chromosome Banding Chromosome Deletion Chromosome Mapping Chromosomes ultrastructure Drosophila melanogaster enzymology genetics Female GTP Cyclohydrolase genetics Gene Rearrangement Genes, Lethal Male Mutation Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0091139 97132600 8978052 1997 03 31 1997 03 31 2002 11 01

0016-6731 144 4 1996 Dec Regulation of the gene Sex-lethal: a comparative analysis of Drosophila melanogaster and Drosophila subobscura. 1653-64 The Drosophila gene Sex-lethal (Sxl) controls the processes of sex determination and dosage compensation. A Drosophila subobscura genomic fragment containing all the exons and the late and early promotors in the Sxl gene of D. melanogaster was isolated. Early Sxl expression in D. subobscura seems to be controlled at the transcriptional level, possibly by the X:A signal. In the region upstream of the early Sxl transcription initiation site are two conserved regions suggested to be involved in the early activation of Sxl. Late Sxl expression in D. subobscura produces four transcripts in adult females and males. In males, the transcripts have an additional exon which contains three translational stop codons so that a truncated, presumably nonfunctional Sxl protein is produced. The Sxl pre-mRNA of D. subobscura lacks the poly-U sequence presented at the polypirimidine tract of the 3' splice site of the male-specific exon present in D. melanogaster. Introns 2 and 3 contain the Sxl-binding poly-U stretches, whose localization in intron 2 varies but in intron 3 is conserved. The Sxl protein is fully conserved at the amino acid level in both species. Centro de Investigaciones Biológicas (C.S.I.C.), Madrid, Spain. Penalva L O LO Sakamoto H H Navarro-Sabaté A A Sakashita E E Granadino B B Segarra C C Sánchez L L eng GENBANK D84425 X98370 X98371 Journal Article

UNITED STATES Genetics 0374636 0 Insect Hormones 0 RNA-Binding Proteins 0 Sxl protein, Drosophila IM Amino Acid Sequence Animal Base Sequence Comparative Study Drosophila genetics Female Gene Dosage Insect Hormones genetics Male Molecular Sequence Data RNA-Binding Proteins genetics Sequence Analysis Sex Determination (Analysis) Support, Non-U.S. Gov't FBrf0125338 20127880 10660560 2000 03 16 2000 03 16 2003 09 17

0021-9258 275 6 2000 Feb 11 A functional interaction between dorsal and components of the Smt3 conjugation machinery. 4033-40 To identify proteins that regulate the function of Dorsal, a Drosophila Rel family transcription factor, we employed a yeast two-hybrid screen to search for genes encoding Dorsal-interacting proteins. Six genes were identified, including two that encode previously known Dorsal-interacting proteins (Twist and Cactus), three that encode novel proteins, and one that encodes Drosophila Ubc9 (DmUbc9), a protein thought to conjugate the ubiquitin-like polypeptide Smt3 to protein substrates. We have found that DmUbc9 binds and conjugates Drosophila Smt3 (DmSmt3) to Dorsal. In cultured cells, DmUbc9 was found to relieve inhibition of Dorsal nuclear uptake by Cactus, allowing Dorsal to enter the nucleus and activate transcription. The effect of DmUbc9 on Dorsal activity was potentiated by the overexpression of DmSmt3. We have also identified a DmSmt3-activating enzyme, DmSAE1/DmSAE2 and found that it further potentiates Dorsal-mediated activation. Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA. Bhaskar V V Valentine S A SA Courey A J AJ eng GENBANK AF218858 AF218859 AF218860 AF218861 AF218862 AF218863 AF218864 GM07185 GM NIGMS GM44522 GM NIGMS Journal Article

UNITED STATES J Biol Chem 2985121R 0 DNA-Binding Proteins 0 Insect Proteins 0 Luminescent Proteins 0 Nuclear Proteins 0 Phosphoproteins 0 SMT3A protein 0 Transcription Factors 0 Ubiquitins 0 dorsal protein, Drosophila 0 uba2 protein, Drosophila 147336-22-9 green fluorescent protein 149059-01-8 cactus protein, Drosophila EC 6. Ligases EC 6.3.2.- Smt3-activating enzyme, Drosophila EC 6.3.2.- ubiquitin-conjugating enzyme UBC9 IM Amino Acid Sequence Animal Body Patterning Cell Line Cell Nucleus metabolism Cloning, Molecular DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology Gene Expression Regulation, Developmental Insect Proteins genetics metabolism Ligases chemistry genetics Luminescent Proteins Microscopy, Fluorescence Molecular Sequence Data Nuclear Proteins analysis genetics metabolism Phosphoproteins genetics metabolism Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Ubiquitins genetics metabolism Yeasts FBrf0103029 98256432 9592147 1998 07 20 1998 07 20 2002 11 01

0305-1048 26 11 1998 Jun 1 Activities of the Sex-lethal protein in RNA binding and protein:protein interactions. 2625-37 The Drosophila sex determination gene Sex-lethal (Sxl) controls its own expression, and the expression of downstream target genes such as transformer , by regulating pre-mRNA splicing and mRNA translation. Sxl codes an RNA-binding protein that consists of an N-terminus of approximately 100 amino acids, two 90 amino acid RRM domains, R1 and R2, and an 80 amino acid C-terminus. In the studies reported here we have examined the functional properties of the different Sxl protein domains in RNA binding and in protein:protein interactions. The two RRM domains are responsible for RNA binding. Specificity in the recognition of target RNAs requires both RRM domains, and proteins which consist of the single domains or duplicated domains have anomalous RNA recognition properties. Moreover, the length of the linker between domains can affect RNA recognition properties. Our results indicate that the two RRM domains mediate Sxl:Sxl protein interactions, and that these interactions probably occur both in cis and trans. We speculate that cis interactions between R1 and R2 play a role in RNA recognition by the Sxl protein, while trans interactions stabilize complex formation on target RNAs that contain two or more closely spaced binding sites. Finally, we show that the interaction of Sxl with the snRNP protein Snf is mediated by the R1 RRM domain. Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA. Samuels M M Deshpande G G Schedl P P eng Journal Article

ENGLAND Nucleic Acids Res 0411011 0 RNA-Binding Proteins 0 Ribonucleoprotein, U1 Small Nuclear 0 SNF protein 0 Sxl protein, Drosophila 63231-63-0 RNA IM Amino Acid Sequence Animal Binding Sites Drosophila melanogaster metabolism Molecular Sequence Data Precipitin Tests RNA metabolism RNA-Binding Proteins genetics metabolism Ribonucleoprotein, U1 Small Nuclear metabolism Support, U.S. Gov't, P.H.S. FBrf0131278 20519452 11063693 2000 11 21 2001 01 04

0016-6731 156 3 2000 Nov The correlation between intron length and recombination in drosophila. Dynamic equilibrium between mutational and selective forces. 1175-90 Intron length is negatively correlated with recombination in both Drosophila melanogaster and humans. This correlation is not likely to be the result of mutational processes alone: evolutionary analysis of intron length polymorphism in D. melanogaster reveals equivalent ratios of deletion to insertion in regions of high and low recombination. The polymorphism data do reveal, however, an excess of deletions relative to insertions (i.e., a deletion bias), with an overall deletion-to-insertion events ratio of 1.35. We propose two types of selection favoring longer intron lengths. First, the natural mutational bias toward deletion must be opposed by strong selection in very short introns to maintain the minimum intron length needed for the intron splicing reaction. Second, selection will favor insertions in introns that increase recombination between mutations under the influence of selection in adjacent exons. Mutations that increase recombination, even slightly, will be selectively favored because they reduce interference among selected mutations. Interference selection acting on intron length mutations must be very weak, as indicated by frequency spectrum analysis of Drosophila intron length polymorphism, making the equilibrium for intron length sensitive to changes in the recombinational environment and population size. One consequence of this sensitivity is that the advantage of longer introns is expected to decrease inversely with the rate of recombination, thus leading to a negative correlation between intron length and recombination rate. Also in accord with this model, intron length differs between closely related Drosophila species, with the longest variant present more often in D. melanogaster than in D. simulans. We suggest that the study of the proposed dynamic model, taking into account interference among selected sites, might shed light on many aspects of the comparative biology of genome sizes including the C value paradox. Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA. jcomeron@midway.uchicago.edu Comeron J M JM Kreitman M M eng GM39355 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Codon IM Animal Codon genetics Computer Simulation Confidence Intervals Drosophila genetics Drosophila melanogaster genetics Female Genes, Insect Human Introns Male Models, Genetic Mutation Polymorphism (Genetics) Recombination, Genetic Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0137038 21394627 11463375 2001 08 15 2001 08 30 2002 11 08

1097-2765 7 3 2001 Mar Yb modulates the divisions of both germline and somatic stem cells through piwi- and hh-mediated mechanisms in the Drosophila ovary. 497-508 The coordinated division of distinctive types of stem cells within an organ is crucial for organogenesis and homeostasis. Here we show genetic interactions among fs(1)Yb (Yb), piwi, and hedgehog (hh) that regulate the division of both germline stem cells (GSCs) and somatic stem cells (SSCs), the two constituent stem cell populations of the Drosophila ovary. Yb is required for both GSC and SSC divisions; loss of Yb function eliminates GSCs and reduces SSC division, while Yb overexpression increases GSC number and causes SSC overproliferation. We also show that Yb acts via the piwi- and hh-mediated signaling pathways that emanate from the same signaling cells to control GSC and SSC division, respectively. hh signaling also has a minor effect in GSC division. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. King F J FJ Szakmary A A Cox D N DN Lin H H eng HD33760 HD NICHD Journal Article

United States Mol Cell 9802571 0 Insect Proteins 0 Membrane Proteins 0 Proteins 0 patched protein, Drosophila 0 piwi protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Cell Division Clone Cells cytology metabolism Drosophila melanogaster cytology genetics metabolism Female Gene Expression Gene Expression Regulation, Developmental Germ Cells cytology metabolism Immunohistochemistry Insect Proteins genetics metabolism Membrane Proteins genetics metabolism Models, Biological Mutation genetics Ovary cytology metabolism Proteins genetics metabolism Signal Transduction Stem Cells cytology metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0075983 95217177 7702596 1995 05 03 1995 05 03 2000 12 18

0265-9247 17 1 1995 Jan Moving up the hierarchy: a hypothesis on the evolution of a genetic sex determination pathway. 71-7 A hypothesis on the evolutionary origin of the genetic pathway of sex determination in the nematode Caenorhabditis elegans is presented here. It is suggested that the pathway arose in steps, driven by frequency-dependent selection for the minority sex at each step, and involving the sequential acquisition of dominant negative, neomorphic genetic switches, each one reversing the action of the previous one. A central implication is that the genetic pathway evolved in reverse order from the final step in the hierarchy up to the first. The possible applicability of the model to the other well-characterized sex determination pathway, that of Drosophila melanogaster, and to sex determination in mammals, is discussed, along with some potential implications for pathway evolution in general. Finally, the specific molecular and population genetic questions that the model raises are described and some tests are proposed. Company of Biologists, Ltd, New Museums Site, University of Cambridge, UK. Wilkins A S AS eng Journal Article Review Review, Tutorial

ENGLAND Bioessays 8510851 IM Animal Caenorhabditis elegans genetics physiology Evolution Gene Expression Regulation Sex Determination (Analysis) 46 FBrf0106865 99126436 9927461 1999 03 09 1999 03 09 2000 12 18

0016-6731 151 2 1999 Feb Identification of genes controlling malpighian tubule and other epithelial morphogenesis in Drosophila melanogaster. 685-95 The Drosophila Malpighian tubule is a model system for studying genetic mechanisms that control epithelial morphogenesis. From a screen of 1800 second chromosome lethal lines, by observing uric acid deposits in unfixed inviable embryos, we identified five previously described genes (barr, fas, flb, raw, and thr) and one novel gene, walrus (wal), that affect Malpighian tubule morphogenesis. Phenotypic analysis of these mutant embryos allows us to place these genes, along with other previously described genes, into a genetic pathway that controls Malpighian tubule development. Specifically, wal affects evagination of the Malpighian tubule buds, fas and thr affect bud extension, and barr, flb, raw, and thr affect tubule elongation. In addition, these genes were found to have different effects on development of other epithelial structures, such as foregut and hindgut morphogenesis. Finally, from the same screen, we identified a second novel gene, drumstick, that affects only foregut and hindgut morphogenesis. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California 90095, USA. Liu X X Kiss I I Lengyel J A JA eng HD-09948 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Animal Drosophila melanogaster embryology genetics Epithelium embryology Gene Expression Regulation, Developmental Genes, Insect Malpighian Tubules embryology Morphogenesis genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0049937 89339164 2503422 1989 09 20 1989 09 20 2000 12 18

0016-6731 122 4 1989 Aug Isolation and characterization of dominant female sterile mutations of Drosophila melanogaster. II. Mutations on the second chromosome. 823-35 Twenty-four, second chromosome, dominant female sterile (Fs) mutations in Drosophila are described. Fs(2) were isolated at a frequency of approximately 1 per 1000 EMS-treated chromosomes screened. In comparison the isolation of frequency for second chromosome zygotic recessive lethal mutations was approximately 550 per 1000. Complementation analysis of the Fs(2) revertants showed that the 24 Fs(2) mutations identify 13-15 loci, calculated to be about 65-75% of the second chromosome genes EMS mutable to dominant female sterility. Two of the Fs(2) mutations are useful tools for the dominant female sterile technique: Fs(2)1 for induction and detection of germ-line clones and Fs(2)Ugra for follicle cell clones. Several of the Fs(2) mutations bring about novel mutant phenotypes. Seven of them alter egg shape, whereas the others arrest development primarily at two stages: around fertilization by five Fs(2) and during cleavage divisions [by Fs(2) in three loci]. The remaining that allow development to the larval stage of differentiation include four new dorsal alleles and one dominant torso allele. Analysis of germ-line chimeras revealed that with two exceptions all the Fs(2) mutations are germ-line dependent. The Fs(2) mutations were mapped mainly on the basis of mitotic recombination induced in the female germ-line cells of adult females. That most of the Fs(2) may be gain-of-function mutations is indicated by the unusual behavior of the Fs+ germ-line clones and also by the fact that 90% of the could be induced to revert. Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged. Szabad J J Erdélyi M M Hoffmann G G Szidonya J J Wright T R TR eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosome Mapping Crossing Over (Genetics) Drosophila melanogaster genetics physiology Female Genes, Dominant Genes, Lethal Genetic Complementation Test Germ Cells ultrastructure Male Microscopy, Electron Mitosis Mutation Phenotype Support, Non-U.S. Gov't FBrf0160859 22753587 12871911 2003 07 21

0016-6731 164 3 2003 Jul A new genetic locus controlling growth and proliferation in Drosophila melanogaster. 1015-25 Multicellular organisms grow through both proliferation and growth of their individual cells. We have conducted a P-element-based misexpression screen for genes whose upregulation alters wing disc growth during development. One particular group of four P elements, all inserted at cytological location 61C7-8, exhibited specific overgrowth upon misexpression in proliferating imaginal tissues. Clonal analysis revealed that upon misexpression, cell number was increased but cell size was not affected, indicating that cell growth and proliferation were induced in a coordinate manner. Loss of function at the locus produced small flies with reduced cell number, consistent with the presence of a gene encoding a positive growth regulator. We characterized a new transcription unit initiating in a region adjacent to the P insertions, which generated a complex series of polyadenylated transcripts. Although these RNAs were induced in response to misexpression, none was sufficient by itself to recapitulate overgrowth when overexpressed. This suggested either that a particular combination of these transcripts was necessary or that other sequences are involved. Institute for Signaling, Developmental Biology and Cancer Research, UMR6543 CNRS, Parc Valrose, 06108 Nice Cedex 2, France. Raisin Sophie S Pantalacci Sophie S Breittmayer Jean-Philippe JP Léopold Pierre P eng Journal Article

United States Genetics 0374636 IM FBrf0147055 21898320 11901120 2002 03 19 2002 09 06

0016-6731 160 3 2002 Mar A misexpression study examining dorsal thorax formation in Drosophila melanogaster. 1035-50 We studied thorax formation in Drosophila melanogaster using a misexpression screen with EP lines and thoracic Gal4 drivers that provide a genetically sensitized background. We identified 191 interacting lines showing alterations of thoracic bristles (number and/or location), thorax and scutellum malformations, lethality, or suppression of the thoracic phenotype used in the screen. We analyzed these lines and showed that known genes with different functional roles (selector, prepattern, proneural, cell cycle regulation, lineage restriction, signaling pathways, transcriptional control, and chromatin organization) are among the modifier lines. A few lines have previously been identified in thorax formation, but others, such as chromatin-remodeling complex genes, are novel. However, most of the interacting loci are uncharacterized, providing a wealth of new genetic data. We also describe one such novel line, poco pelo (ppo), where both misexpression and loss-of-function phenotypes are similar: loss of bristles and scutellum malformation. Department of Developmental Neurobiology and Neurophysiology, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, 76230, México. Peña-Rangel María Teresa MT Rodriguez Isabel I Riesgo-Escovar Juan Rafael JR eng Journal Article

United States Genetics 0374636 0 Transcription Factors 0 pannier protein IM Animal Drosophila melanogaster anatomy & histology genetics growth & development Gene Expression Profiling Gene Expression Regulation physiology Phenotype Signal Transduction Support, Non-U.S. Gov't Thorax abnormalities growth & development Transcription Factors genetics metabolism FBrf0151842 22213265 12225669 2002 09 12 2003 06 16

0960-9822 12 17 2002 Sep 3 The fusome and microtubules enrich Par-1 in the oocyte, where it effects polarization in conjunction with Par-3, BicD, Egl, and dynein. 1524-8 After its specification, the Drosophila oocyte undergoes a critical polarization event that involves a reorganization of the microtubules (MT) and relocalization of the determinant Orb within the oocyte. This polarization requires Par-1 kinase and the PDZ-containing Par-3 homolog, Bazooka (Baz). Par-1 has been observed on the fusome, which degenerates before the onset of oocyte polarization. How Par-1 acts to polarize the oocyte has been unclear. Here we show that Par-1 becomes restricted to the oocyte in a MT-dependent fashion after disappearance of the fusome. At the time of polarization, the kinase itself and the determinant BicaudalD (BicD) are relocalized from the anterior to the posterior of the oocyte. Par-1 and BicD are interdependent and require MT and the minus end-directed motor Dynein for their relocalization. We show that baz is required for Par-1 relocalization within the oocyte and that the distributions of Baz and Par-1 in the Drosophila oocyte are complementary and strikingly reminiscent of the two PAR proteins in the C. elegans embryo. We propose that, through the combined actions of the fusome, MT, and Baz, Par-1 is selectively enriched and localized within the oocyte, where, in conjunction with BicD, Egalitarian (Egl), and Dynein, it acts on the MT cytoskeleton to effect polarization. Developmental Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Vaccari Thomas T Ephrussi Anne A eng Journal Article

England Curr Biol 9107782 0 Carrier Proteins 0 Drosophila Proteins 0 Egg Proteins 0 Molecular Motors 0 RNA-Binding Proteins 0 bazooka protein 0 oo18 RNA-binding protein, Drosophila 0 sycaudalD protein, Drosophila EC 2.7.1.- Par-1 protein, Drosophila EC 2.7.1.37 Protein Kinases EC 3.6.1.33 Dynein ATPase IM Animal Carrier Proteins genetics physiology Cell Polarity physiology Cytoskeleton ultrastructure Drosophila Proteins genetics metabolism physiology Drosophila melanogaster cytology genetics physiology Dynein ATPase genetics physiology Egg Proteins genetics physiology Microtubules physiology Molecular Motors Oocytes metabolism ultrastructure Oogenesis Organelles ultrastructure Protein Kinases genetics physiology RNA-Binding Proteins metabolism Support, Non-U.S. Gov't FBrf0077021 94344777 7915032 1994 09 21 1994 09 21 2003 06 16

0305-1048 22 15 1994 Aug 11 Mcp and Fab-7: molecular analysis of putative boundaries of cis-regulatory domains in the bithorax complex of Drosophila melanogaster. 3138-46 A very large cis-regulatory region of approximately 300 kb is responsible for the complex patterns of expression of the three homeotic genes of the bithorax complex Ubx, abd-A and Abd-B. This region can be subdivided in nine parasegment-specific regulatory subunits. Recent genetic and molecular analysis has revealed the existence of two novel cis-regulatory elements Mcp and Fab-7. Mcp is located between iab-4 and iab-5, the parasegment-specific regulatory subunits which direct Abd-B in parasegments 9 and 10. Similarly, Fab-7 is located between iab-6 and iab-7, the parasegment 11 and 12-specific regulatory units. Mcp and Fab-7 appear to function as domain boundaries that separate adjacent cis-regulatory units. We report the analysis of two new Mcp mutant deletions (McpH27 and McpB116) that allow us to localize sequences essential for boundary function to a approximately 0.4 kb DNA segment. These essential sequences closely coincide to a approximately 0.3 kb nuclease hypersensitive region in chromatin. We also show that sequences contributing to the Fab-7 boundary appear to be spread over a larger stretch of DNA, but like Mcp have an unusual chromatin structure. Department of Zoology and Animal Biology, University of Geneva, Switzerland. Karch F F Galloni M M Sipos L L Gausz J J Gyurkovics H H Schedl P P eng GENBANK X78982 X78983 Journal Article

ENGLAND Nucleic Acids Res 0411011 0 Abd-B proteins, Drosophila 0 Chromatin 0 DNA-Binding Proteins 0 Insect Hormones 0 Proteins 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila IM Fab-7 Mcp Animal Base Sequence Chromatin chemistry DNA-Binding Proteins genetics Drosophila melanogaster genetics Gene Deletion Genes, Homeobox Insect Hormones genetics Molecular Sequence Data Mutagenesis Proteins genetics Regulatory Sequences, Nucleic Acid Sequence Analysis, DNA Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Thorax FBrf0090824 94116069 8287482 1994 02 24 1994 02 24 2000 12 18

0092-8674 76 1 1994 Jan 14 Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs. 89-102 The segment polarity genes hedgehog and engrailed are expressed in identical posterior-compartment-specific patterns in both Drosophila embryos and imaginal discs. We show here that the hedgehog protein is secreted, and it can cross embryo parasegment borders and the anterior-posterior compartment border of imaginal discs to neighboring cells that express neither engrailed nor hedgehog. In these cells, it is localized in discrete punctate structures that are sequestered within the polarized epithelium. Analysis of animals that have expressed hedgehog ectopically, or of a mutant that expresses hedgehog abnormally in the anterior compartment of the wing disc, indicates that hedgehog is involved in regulating patched. In the embryo, hedgehog regulation of patched apparently facilitates patched and wingless expression. In the discs, hedgehog regulation of patched and other genes in the anterior compartment helps to establish the proximodistal axis. We propose that the cell-cell communication mediated by hedgehog links the special properties of compartment borders with specification of the proximodistal axis in imaginal development. Department of Biochemistry and Biophysics, University of California, San Francisco 94143. Tabata T T Kornberg T B TB eng Journal Article

UNITED STATES Cell 0413066 0 Proteins 149291-21-4 hedgehog protein, Drosophila 17090-79-8 Monensin IM Animal Blotting, Western Cell Line, Transformed Drosophila embryology genetics Drosophila melanogaster Embryo, Nonmammalian drug effects physiology Gene Expression Models, Biological Monensin pharmacology Protein Processing, Post-Translational Proteins biosynthesis metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Wing physiology FBrf0111378 99415814 10485852 1999 10 12 1999 10 12 2002 10 21

0890-9369 13 17 1999 Sep 1 The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs. 2315-27 The tissue polarity mutants in Drosophila include a set of conserved gene products that appear to be involved in the control of cytoskeletal architecture. Here we show that the tissue polarity gene prickle (pk) encodes a protein with a triple LIM domain and a novel domain that is present in human, murine, and Caenorhabditis elegans homologs which we designate PET. Three transcripts have been identified, pk, pkM, and sple, encoding 93-, 100-, and 129-kD conceptual proteins, respectively. The three transcripts span 70 kb and share 6 exons that contain the conserved domains. The pk and sple transcripts are expressed with similar tissue-specific patterns but have qualitatively different activities. The phenotypes of pk mutants, and transgenic flies in which the different isoforms are overexpressed show that the balance between Pk and Sple is critical for the specification of planar polarity. In addition, these phenotypes suggest a tessellation model in which the alignment of wing hairs is dependent on cell shape and need not reflect fine-grained positional information. Lack of both pk and sple transcripts gives a phenotype affecting the whole body surface that is similar to those of dishevelled and frizzled (fz) suggesting a functional relationship between pk and fz signaling. Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. dg27@mole.bio.cam.ac.uk Gubb D D Green C C Huen D D Coulson D D Johnson G G Tree D D Collier S S Roote J J eng GENBANK AJ236864 AJ243708 AJ243710 Journal Article

UNITED STATES Genes Dev 8711660 0 DNA-Binding Proteins 0 Insect Proteins 0 Protein Isoforms 0 prickle protein, Drosophila IM Amino Acid Sequence Animal Body Patterning Caenorhabditis elegans genetics Conserved Sequence DNA-Binding Proteins chemistry genetics metabolism Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian physiology Gene Expression Regulation, Developmental Human Insect Proteins chemistry genetics metabolism Mice Molecular Sequence Data Mutagenesis Organ Specificity Protein Isoforms genetics Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't Transcription, Genetic FBrf0058120 94357075 8076518 1994 10 03 1994 10 03 2002 11 01

0950-1991 118 3 1993 Jul Expression of the Sex-lethal gene is controlled at multiple levels during Drosophila oogenesis. 797-812 In addition to controlling somatic sexual development in Drosophila melanogaster, the Sex-lethal (Sxl) gene is required for proper differentiation of female germ cells. To investigate its role in germ-line development, we have examined the expression of Sxl in wild-type ovaries and ovaries that are defective in early steps of germ cell differentiation. As in the soma, the basic mechanism for on/off regulation of Sxl relies on sex-specific processing of its transcripts in germ cells. One class of female-sterile mutations, which includes fs(1)1621 and the tumorous-ovary-producing allele of the ovarian tumor gene, otu1, is defective in the splicing process. These mutants have germ lines with high amounts of Sxl RNA spliced in the male mode and a severe reduction of protein levels in the germ cells. Another class of female-sterile mutations produces a phenotype similar to that seen in fs(1)1621 and otu1 but appears to express normal levels of Sxl protein in the germ cells. However, this second class does not show the changes in protein distribution normally observed in wild-type germ cells. In the wild-type germarium, the non-differentiated germ cells show a strong cytoplasmic accumulation of Sxl protein followed, as the germ cells differentiate, by a dramatic reduction and redistribution of the protein into nuclear foci. Interestingly, two female-sterile alleles of Sxl, Sxlf4 and Sxlf5 belong to the second class, which shows persistent cytoplasmic accumulation of Sxl protein. These Sxl female-sterile mutants encode an altered protein indicating that Sxl regulates processes that eventually lead to the changes in Sxl protein distribution. Lastly, we demonstrate that during the final stages of oogenesis several mechanisms must operate to prevent the progeny from inheriting Sxl protein. Conceivably, this regulation safeguards the inadvertent activation of the Sxl autoregulatory feedback loop in the male zygote. Department of Molecular Biology, Moffett laboratory, Princeton University, NJ 08544. Bopp D D Horabin J I JI Lersch R A RA Cline T W TW Schedl P P eng Journal Article

ENGLAND Development 8701744 0 Insect Hormones 0 Sxl protein, Drosophila IM Sxl Sxl<up>f4</up> Sxl<up>f5</up> bam fs(l)1621 fu otu<up>1</up> Animal Base Sequence Cell Differentiation Drosophila melanogaster genetics physiology Female Gene Expression Regulation Genes, Lethal Genes, Structural, Insect Infertility, Female genetics Insect Hormones biosynthesis genetics physiology Male Molecular Sequence Data Mutation Oogenesis genetics Ovarian Neoplasms genetics Ovary cytology Polymerase Chain Reaction RNA Splicing Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0054060 91160973 1900493 1991 04 17 1991 04 17 2002 11 01

0890-9369 5 3 1991 Mar Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. 403-15 The binary switch gene Sex-lethal (Sxl) must be on in females and off in males to allow the proper elaboration of the appropriate sexual developmental pathway in Drosophila melanogaster. Previous studies suggested a mechanism in which the on/off regulation of Sxl occurs post-transcriptionally at the level of RNA splicing. A critical prediction of this model is that functional Sxl proteins are absent in males but present in females. In this report we show that the expected full-length proteins are only present in female animals. Multiple forms of Sxl protein are found in females, some of which are expressed in a stage- and tissue-specific pattern. Consistent with a role of Sxl proteins in regulating alternate splicing, the proteins are localized in the nucleus where they exhibit a punctate staining pattern. Surprisingly, several minor Sxl proteins appear to be present in specific tissues of both sexes of adults. The possible origin of these species is discussed. We also show that Sxl expression in the early embryo is sex specific and depends on maternal daughterless and zygotic sisterless-b activity in accordance with the established roles of these genes as positive regulators of Sxl. The onset of Sxl expression in the germ line occurs later than that in the soma. Department of Molecular Biology, Princeton University, New Jersey 08544-1014. Bopp D D Bell L R LR Cline T W TW Schedl P P eng Journal Article

UNITED STATES Genes Dev 8711660 0 Insect Hormones 0 Proteins 0 Sxl protein, Drosophila IM Sxl Animal Cell Nucleus chemistry Drosophila melanogaster analysis embryology genetics growth & development Female Gene Expression Genes, Lethal Genes, Switch Insect Hormones analysis genetics Male Proteins analysis genetics Sex Determination (Analysis) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0148947 22011831 12015974 2002 05 17 2002 06 17 2003 06 16

1534-5807 2 5 2002 May In vivo imaging reveals different cellular functions for FGF and Dpp signaling in tracheal branching morphogenesis. 677-83 In the developing tracheal system of Drosophila melanogaster, six major branches arise by guided cell migration from a sac-like structure. The chemoattractant Branchless/FGF (Bnl) appears to guide cell migration and is essential for the formation of all tracheal branches, while Decapentaplegic (Dpp) signaling is strictly required for the formation of a subset of branches, the dorsal and ventral branches. Using in vivo confocal video microscopy, we find that the two signaling systems affect different cellular functions required for branching morphogenesis. Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such, and Dpp controls cellular functions allowing branch morphogenesis and outgrowth. Abteilung Zellbiologie, Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Ribeiro Carlos C Ebner Andreas A Affolter Markus M eng Journal Article

United States Dev Cell 101120028 0 Drosophila Proteins 0 Insect Proteins 0 branchless protein, Drosophila 0 dpp protein, Drosophila 62031-54-3 Fibroblast Growth Factors IM Animal Animals, Genetically Modified Drosophila Proteins genetics physiology Drosophila melanogaster genetics growth & development physiology Fibroblast Growth Factors genetics physiology Genes, Insect Insect Proteins genetics physiology Morphogenesis Pseudopodia physiology Signal Transduction Support, Non-U.S. Gov't Trachea growth & development FBrf0138358 21417205 11526075 2001 08 29 2001 10 11

0950-1991 128 14 2001 Jul The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development. 2689-97 The onset of pattern formation in the developing Drosophila retina begins with the initiation of the morphogenetic furrow, the leading edge of a wave of retinal development that transforms a uniform epithelium, the eye imaginal disc into a near crystalline array of ommatidial elements. The initiation of this wave of morphogenesis is under the control of the secreted morphogens Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor Receptor and Notch signaling cascades are crucial components that are also required to initiate retinal development. We also show that the initiation of the morphogenetic furrow is the sum of two genetically separable processes: (1) the 'birth' of pattern formation at the posterior margin of the eye imaginal disc; and (2) the subsequent 'reincarnation' of retinal development across the epithelium. Department of Cell Biology, Emory University School of Medicine, 1648 Pierce Drive, Atlanta, GA 30322-3030, USA. Kumar J P JP Moses K K eng 5 F32 ET06763 PHS RO1 EY-12537 EY NEI Journal Article

England Development 8701744 0 Insect Proteins 0 Membrane Proteins 0 Proto-Oncogene Proteins 0 dpp protein, Drosophila 0 notch protein 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Drosophila melanogaster genetics growth & development Eye growth & development Insect Proteins genetics metabolism Membrane Proteins genetics metabolism physiology Morphogenesis Proto-Oncogene Proteins genetics metabolism Receptor, Epidermal Growth Factor genetics metabolism physiology Signal Transduction Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0037664 83026558 6813058 1982 12 21 1982 12 21 2000 12 18

0009-5915 85 4 1982 Mutants affecting position-effect heterochromatinization in Drosophila melanogaster. 539-51 The dominant suppressor Su(var)b101 and the dominant enhancer En(var)c101 were found to affect significantly white variegation in a strongly variegating line of the Wm4 chromosome (Wm4h) which has been used as standard rearrangement for a genetic dissection of position-effect variegation (Reuter and Wolff, 1981). Both mutations were also shown to affect position-effect heterochromatisation in T (1 ; 4)Wm258-21 and variegation in all the rearrangements tested (white, brown, scute and bobbed variegation). These results suggest that the genes identified encode functions essential for the manifestation of gene inactivation in position-effect rearrangements. It seems also reasonable to assume that in all the rearrangements tested identical heterochromatisation processes lead to inactivation of the genes whose phenotype is variegated. Reuter G G Werner W W Hoffmann H J HJ eng Journal Article

GERMANY, WEST Chromosoma 2985138R 0 Heterochromatin IM Animal Chromosome Aberrations Chromosome Mapping Crosses, Genetic Drosophila melanogaster genetics Female Genes, Dominant Genotype Heterochromatin physiology Male Mutation Suppression, Genetic X Chromosome FBrf0073755 94232191 8177220 1994 06 06 1994 06 06 2000 12 18

0026-8925 243 2 1994 Apr Molecular analysis of cubitus interruptus (ci) mutations suggests an explanation for the unusual ci position effects. 234-43 The cubitus interruptus (ci) locus of Drosophila melanogaster is located proximally on chromosome 4. In ci mutants cubital wing veins are interrupted or absent. We have cloned this locus using a gypsy element associated with the ci1 mutation. Analysis of all extant ci mutations reveals that they contain conspicuous molecular alterations within a 13.7 kb region. Of the four homozygous viable mutations, three (ci1, ci361, ciw) have single insertions, while one (ci57g) has a small deletion, all located within a more restricted 1 kb region. The dominant mutations, ciD and Ce2 each contain two insertions within the 13.7 kb region. All these molecular alterations are located upstream of a transcript previously associated with the ciD mutation and thought to derive from a segment polarity gene. We induced revertants of the dominant ci phenotype (wing vein interruption) in ciD and found molecular alterations in this transcript (the ci+ transcript) in two revertant alleles, thereby demonstrating this transcript's involvement in the ci phenotype. The locations of the molecular alterations, together with the results of the ciD reversion experiment, provide a connection between the dominant and recessive ci mutations and argue that all are likely to be alleles of the same complex locus, ci, not two separate loci as previously proposed. The ci phenotype of dominant and recessive mutations can be explained by inappropriate expression of the ci+ transcript in the posterior wing compartment where the cubital vein is affected, while loss of ci+ function generates recessive lethality. Lack of repression of ci+ transcription, through a pairing-dependent, trans-acting silencer element, can explain the unusual position effects associated with ci (the Dubinin effect). Department of Genetics, University of Alberta, Edmonton, Canada. Locke J J Tartof K D KD eng CA-06927 CA NCI Journal Article

GERMANY Mol Gen Genet 0125036 0 RNA, Messenger 0 Trans-Activators IM Animal Blotting, Northern Chromosome Walking Drosophila melanogaster genetics Female Gene Library Genes, Structural, Insect Genetic Complementation Test In Situ Hybridization Male Mutagenesis, Insertional Mutation RNA, Messenger genetics Restriction Mapping Sequence Deletion Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Suppression, Genetic Trans-Activators Wing abnormalities FBrf0111876 20020328 10552039 1999 12 10 1999 12 10 2000 12 18

0022-2844 49 5 1999 Nov Absence of protein polymorphism in the Ras genes of Drosophila melanogaster. 583-90 Sequence analysis of 27 alleles of each of the three Ras-related genes in Drosophila melanogaster indicates that they all have low levels of polymorphism but may experience slightly different evolutionary pressures. No amino acid replacement substitutions were indicated in any of the sequences, or in the sibling species D. simulans and D. mauritiana. The Dras1 gene, which is the major ras homologue in Drosophila, has less within-species variation in D. melanogaster relative to the amount of divergence from the sibling species than does Dras2, although the contrast was not significant by the HKA test. Dras2 appears to be maintaining two classes of haplotype in D. melanogaster, one of which is closer to the alleles observed in the sibling species, suggesting that this is not likely to be a pseudogene despite the absence of a mutant phenotype. Although differences in level of expression may affect the function of the genes, it is concluded that genetic variation in the Ras signal transduction pathways cannot be attributed to catalytic variation in the Ras proteins. Department of Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA. Gasperini R R Gibson G G eng Journal Article

UNITED STATES J Mol Evol 0360051 0 DNA Primers 0 Insect Proteins 9007-49-2 DNA EC 3.6.1.- ras Proteins IM Alleles Animal Base Sequence Comparative Study DNA genetics DNA Primers genetics Drosophila genetics Drosophila melanogaster genetics Evolution, Molecular Genes, Insect Genes, ras Insect Proteins genetics Polymorphism (Genetics) Sequence Homology, Nucleic Acid Species Specificity Support, Non-U.S. Gov't Variation (Genetics) ras Proteins genetics FBrf0144882 21838684 11850406 2002 02 18 2002 04 05

0890-9369 16 4 2002 Feb 15 KSR is a scaffold required for activation of the ERK/MAPK module. 427-38 Mechanisms that regulate signal propagation through the ERK/MAPK pathway are still poorly understood. Several proteins are suspected to play critical roles in this process. One of these is Kinase Suppressor of Ras (KSR), a component previously identified in RAS-dependent genetic screens in Drosophila and Caenorhabditis elegans. Here, we show that KSR functions upstream of MEK within the ERK/MAPK module. In agreement with this, we found that KSR facilitates the phosphorylation of MEK by RAF. We further show that KSR associates independently with RAF and MEK, and that these interactions lead to the formation of a RAF/MEK complex, thereby positioning RAF in close proximity to its substrate MEK. These findings suggest that KSR functions as a scaffold that assembles the RAF/MEK functional pair. Clinical Research Institute of Montreal, Laboratory of Intracellular Signaling, Montreal, PQ Canada H2W 1R7. Roy François F Laberge Gino G Douziech Mélanie M Ferland-McCollough David D Therrien Marc M eng Journal Article

United States Genes Dev 8711660 0 Drosophila Proteins 0 MAP Kinase Signaling System 0 Macromolecular Systems 0 Recombinant Fusion Proteins EC 2.7.1.- KSR-1 protein kinase EC 2.7.1.37 Mitogen-Activated Protein Kinase Kinases EC 2.7.1.37 Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 2.7.10.- p74(raf-1) protein EC 3.6.1.- ras Proteins IM Animal Cells, Cultured Drosophila Proteins genetics physiology Drosophila melanogaster cytology enzymology genetics MAP Kinase Signaling System physiology Macromolecular Systems Mitogen-Activated Protein Kinase Kinases metabolism Phosphorylation Protein Kinases genetics physiology Protein Processing, Post-Translational Proto-Oncogene Proteins c-raf physiology Recombinant Fusion Proteins physiology Support, Non-U.S. Gov't Transfection ras Proteins physiology FBrf0138370 21430856 11546742 2001 09 07 2001 10 18 2003 06 16

0950-1991 128 17 2001 Sep Successive specification of Drosophila neuroblasts NB 6-4 and NB 7-3 depends on interaction of the segment polarity genes wingless, gooseberry and naked cuticle. 3253-61 The Drosophila central nervous system derives from neural precursor cells, the neuroblasts (NBs), which are born from the neuroectoderm by the process of delamination. Each NB has a unique identity, which is revealed by the production of a characteristic cell lineage and a specific set of molecular markers it expresses. These NBs delaminate at different but reproducible time points during neurogenesis (S1-S5) and it has been shown for early delaminating NBs (S1/S2) that their identities depend on positional information conferred by segment polarity genes and dorsoventral patterning genes. We have studied mechanisms leading to the fate specification of a set of late delaminating neuroblasts, NB 6-4 and NB 7-3, both of which arise from the engrailed (en) expression domain, with NB 6-4 delaminating first. In contrast to former reports, we did not find any evidence for a direct role of hedgehog in the process of NB 7-3 specification. Instead, we present evidence to show that the interplay of the segmentation genes naked cuticle (nkd) and gooseberry (gsb), both of which are targets of wingless (wg) activity, leads to differential commitment to NB 6-4 and NB 7-3 cell fate. In the absence of either nkd or gsb, one NB fate is replaced by the other. However, the temporal sequence of delamination is maintained, suggesting that formation and specification of these two NBs are under independent control. Institut für Genetik, Universität Mainz, Saarstrasse 21, D-55122 Mainz, Germany. Deshpande N N Dittrich R R Technau G M GM Urban J J eng Journal Article

England Development 8701744 0 Homeodomain Proteins 0 Insect Proteins 0 Proto-Oncogene Proteins 0 Trans-Activators 0 Transcription Factors 0 engrail protein, Drosophila 0 gsb protein, Drosophila 0 naked cuticle protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Body Patterning genetics physiology Cell Differentiation Central Nervous System embryology Drosophila melanogaster embryology genetics metabolism Homeodomain Proteins metabolism physiology Insect Proteins metabolism physiology Neurons cytology Proto-Oncogene Proteins metabolism Stem Cells cytology Support, Non-U.S. Gov't Time Factors Trans-Activators metabolism Transcription Factors metabolism physiology FBrf0110704 99370682 10442094 1999 09 07 1999 09 07 2003 06 16

1420-682X 55 8-9 1999 Jul Germline development in vertebrates and invertebrates. 1141-63 In all animals information is passed from parent to offspring via the germline, which segregates from the soma early in development and undergoes a complex developmental program to give rise to the adult gametes. Many aspects of germline development have been conserved throughout the animal kingdom. Here we review the unique properties of germ cells, the initial determination of germ cell fates, the maintenance of germ cell identity, the migration of germ cells to the somatic gonadal primordia and the proliferation of germ cells during development invertebrates and invertebrates. Similarities in germline development in such diverse organisms as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis and Mus musculus will be highlighted. Department of Biology, McGill University, Montréal, Québec, Canada. Saffman E E EE Lasko P P eng Journal Article Review Review, Academic

SWITZERLAND Cell Mol Life Sci 9705402 0 Helminth Proteins 0 Insect Proteins 0 RNA-Binding Proteins 0 oskar protein, Drosophila 139568-71-1 staufen protein, Drosophila 63231-63-0 RNA EC 2.7.7.- RNA Helicases EC 2.7.7.- vasa protein IM Animal Caenorhabditis elegans embryology genetics growth & development Cell Lineage Cell Movement Cell Polarity Drosophila melanogaster embryology genetics growth & development Embryo, Nonmammalian physiology Female Gene Expression Regulation, Developmental physiology Germ Cells physiology Gonads embryology growth & development Helminth Proteins physiology Human Insect Proteins physiology Invertebrates embryology genetics growth & development Larva Male Mammals embryology genetics growth & development Mice Oogenesis RNA metabolism RNA Helicases physiology RNA-Binding Proteins physiology Vertebrates embryology genetics growth & development Xenopus laevis embryology growth & development 230 FBrf0104517 98365470 9700164 1998 09 04 1998 09 04 2003 06 16

0021-9525 142 3 1998 Aug 10 ZW10 helps recruit dynactin and dynein to the kinetochore. 763-74 Mutations in the Drosophila melanogaster zw10 gene, which encodes a conserved, essential kinetochore component, abolish the ability of dynein to localize to kinetochores. Several similarities between the behavior of ZW10 protein and dynein further support a role for ZW10 in the recruitment of dynein to the kinetochore: (a) in response to bipolar tension across the chromosomes, both proteins mostly leave the kinetochore at metaphase, when their association with the spindle becomes apparent; (b) ZW10 and dynein both bind to functional neocentromeres of structurally acentric minichromosomes; and (c) the localization of both ZW10 and dynein to the kinetochore is abolished in cells mutant for the gene rough deal. ZW10's role in the recruitment of dynein to the kinetochore is likely to be reasonably direct, because dynamitin, the p50 subunit of the dynactin complex, interacts with ZW10 in a yeast two-hybrid screen. Since in zw10 mutants no defects in chromosome behavior are observed before anaphase onset, our results suggest that dynein at the kinetochore is essential for neither microtubule capture nor congression to the metaphase plate. Instead, dynein's role at the kinetochore is more likely to be involved in the coordination of chromosome separation and/or poleward movement at anaphase onset. Section of Genetics and Development, Cornell University, Ithaca, New York 14853-2703, USA. Starr D A DA Williams B C BC Hays T S TS Goldberg M L ML eng GM 07617 GM NIGMS GM 48430 GM NIGMS Journal Article

UNITED STATES J Cell Biol 0375356 0 Insect Proteins 0 Microtubule-Associated Proteins 144198-36-7 dynactin 147979-57-5 mitotic 15 protein, Drosophila EC 3.6.1.33 Dynein ATPase IM Animal Centromere Drosophila melanogaster Dynein ATPase metabolism Human Insect Proteins genetics physiology Kinetochores metabolism Male Meiosis Microtubule-Associated Proteins metabolism Mitosis Mutation Support, U.S. Gov't, P.H.S. FBrf0139771 21468418 11584277 2001 10 03 2001 12 04 2002 11 01

1465-7392 3 10 2001 Oct Drosophila APC2 and Armadillo participate in tethering mitotic spindles to cortical actin. 933-8 Proper positioning of mitotic spindles ensures equal allocation of chromosomes to daughter cells. This often involves interactions between spindle and astral microtubules and cortical actin. In yeast and Caenorhabditis elegans, some of the protein machinery that connects spindles and cortex has been identified but, in most animal cells, this process remains mysterious. Here, we report that the tumour suppressor homologue APC2 and its binding partner Armadillo both play roles in spindle anchoring during the syncytial mitoses of early Drosophila embryos. Armadillo, alpha-catenin and APC2 all localize to sites of cortical spindle attachment. APC2-Armadillo complexes often localize with interphase microtubules. Zeste-white 3 kinase, which can phosphorylate Armadillo and APC, is also crucial for spindle positioning and regulates the localization of APC2-Armadillo complexes. Together, these data suggest that APC2, Armadillo and alpha-catenin provide an important link between spindles and cortical actin, and that this link is regulated by Zeste-white 3 kinase. Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280, USA. McCartney B M BM McEwen D G DG Grevengoed E E Maddox P P Bejsovec A A Peifer M M eng 1F32CA79172 CA NCI 1F32GM19824 GM NIGMS 5T32CA71341 CA NCI GM47857 GM NIGMS Journal Article

England Nat Cell Biol 100890575 0 Actins 0 Cadherins 0 Cytoskeletal Proteins 0 Insect Proteins 0 adenomatous polyposis coli protein 2 0 armadillo protein, Drosophila 138930-21-9 CAP102 EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 shaggy kinase, Drosophila IM Nat Cell Biol. 2001 Oct;3(10):E226-8 11584281 Actins metabolism Animal Cadherins metabolism Cytoskeletal Proteins genetics metabolism Drosophila melanogaster cytology embryology genetics Giant Cells metabolism Human Insect Proteins metabolism Microscopy, Fluorescence Mitosis Mitotic Spindle Apparatus metabolism ultrastructure Protein-Serine-Threonine Kinases metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0087579 96304594 8722781 1996 10 11 1996 10 11 2000 12 18

0016-6731 143 1 1996 May Effects of single P-element insertions on bristle number and viability in Drosophila melanogaster. 277-92 Single P-element mutagenesis was used to construct 1094 lines with P[lArB] inserts on all three major chromosomes in an isogenic background previously free of P elements. The effects of insertions on bristle number and on viability were assessed by comparison to 392 control lines. The variance and effects of P-element inserts on bristle number and viability were larger than those inferred from spontaneous mutations. The distributions of effects on bristle number were symmetrical and highly leptokurtic, such that a few inserts with large effects caused most of the increase in variance. The distribution of effects on viability were negatively skewed and platykurtic. On average, the effects of P-element insertions on bristle number were partly recessive and on viability were completely recessive. P-element inserts with large effects on bristle number tended to have reduced viability, but the correlation between the absolute value of the effects on bristle number and on viability was not strong. Fifty P-element inserts tagging quantitative trait loci (QTLs) with large effects on bristle number were mapped cytogenetically. Two P-element-induced scabrous alleles and five extramacrochaetae alleles were generated. Single P-element mutagenesis is a powerful method for identifying QTLs at the level of genetic locus. Department of Genetics, North Carolina State University, Raleigh 27695-7614, USA. Lyman R F RF Lawrence F F Nuzhdin S V SV Mackay T F TF eng GM-45344 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 Genetic Markers EC 2.7.7.- DNA Nucleotidyltransferases EC 2.7.7.- Transposase IM Analysis of Variance Animal Chromosome Mapping Crosses, Genetic DNA Nucleotidyltransferases biosynthesis DNA Transposable Elements Drosophila melanogaster anatomy & histology genetics physiology Female Genetic Markers Heterozygote Homozygote Male Mutagenesis, Insertional Regression Analysis Support, U.S. Gov't, P.H.S. Transposase Vibrissae FBrf0049904 89357454 2504643 1989 10 12 1989 10 12 2000 12 18

0016-6731 122 2 1989 Jun A tripartite interaction among alleles of Notch, Delta, and Enhancer of split during imaginal development of Drosophila melanogaster. 429-38 A dramatic example of a phenotypic interaction that involves neurogenic loci during Drosophila imaginal development is the synergistic impact of split (spl), a recessive allele of the Notch locus, and E(spl)D, a dominant gain-of-function allele of the Enhancer of split locus, on morphogenesis of the compound eye. Screens for mutations that relieve the enhancing effect of E(spl)D on spl have yielded three classes of mutations: intragenic revertants of the E(spl)D allele, extragenic suppressors that are allelic to the neurogenic gene Delta (Dl) and unlinked extragenic modifiers. Analysis of the suppression of the spl-E(spl)D interaction by various Dl alleles indicates that this modification is sensitive to the dosage of the Dl locus. This tripartite interaction illustrates the combinatorial action of N, Dl and E(spl) during imaginal development. Department of Biology, Indiana University, Bloomington 47405. Shepard S B SB Broverman S A SA Muskavitch M A MA eng Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Drosophila melanogaster embryology genetics Epistasis, Genetic Eye embryology Genes, Dominant Genes, Recessive Genes, Regulator Morphogenesis Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0158737 22501942 12614154 2003 03 04 2003 06 16

0006-2960 42 9 2003 Mar 11 Motor domain mutation traps kinesin as a microtubule rigor complex. 2595-606 Conventional kinesin is a highly processive, microtubule-based motor protein that drives the movement of membranous organelles in neurons. Using in vivo genetics in Drosophila melanogaster, Glu164 was identified as an amino acid critical for kinesin function [Brendza, K. M., Rose, D. J., Gilbert, S. P., and Saxton, W. M. (1999) J. Biol. Chem. 274, 31506-31514]. Glu164 is located at the beta-strand 5a/loop 8b junction of the catalytic core and projects toward the microtubule binding face in close proximity to key residues on beta-tubulin helix alpha12. Substitution of Glu(164) with alanine (E164A) results in a dimeric kinesin with a dramatic reduction in the microtubule-activated steady-state ATPase (5 s(-1) per site versus 22 s(-1) per site for wild-type). Our analysis shows that E164A binds ATP and microtubules with a higher affinity than wild-type kinesin. The rapid quench and stopped-flow results provide evidence that ATP hydrolysis is significantly faster and the precise coordination between the motor domains is disrupted. The data reveal an E164A intermediate that is stalled on the microtubule and cannot bind and hydrolyze ATP at the second head. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. Klumpp Lisa M LM Brendza Katherine M KM Rosenberg John M JM Hoenger Andreas A Gilbert Susan P SP eng GM54141 GM NIGMS K02-AR47841 AR NIAMS Journal Article

United States Biochemistry 0370623 0 Anthranilic Acids 0 Drosophila Proteins 0 Molecular Motors 56-41-7 Alanine 56-65-5 Adenosine Triphosphate 56-86-0 Glutamic Acid 58-64-0 Adenosine Diphosphate 85287-55-4 3'-O-(N-methylanthraniloyl)adenosine 5'-diphosphate 85287-56-5 3'-O-(N-methylanthraniloyl) ATP EC 3.6.1.- Kinesin IM Adenosine Diphosphate analogs & derivatives metabolism Adenosine Triphosphate analogs & derivatives metabolism Alanine genetics Animal Anthranilic Acids metabolism Binding Sites genetics Cattle Dimerization Drosophila Proteins genetics metabolism Electrostatics Glutamic Acid genetics Human Hydrolysis Kinesin genetics metabolism Kinetics Microtubules enzymology genetics Molecular Motors enzymology genetics Mutagenesis, Site-Directed Protein Structure, Tertiary genetics Rats Support, U.S. Gov't, P.H.S. FBrf0042053 86079517 3935319 1986 01 29 1986 01 29 2000 12 18

0092-8674 43 1 1985 Nov The abdominal region of the bithorax complex. 81-96 The homeotic mutations in the right half of the bithorax complex of Drosophila cause segmental transformations in the second through the eighth segments of the fly. A chromosomal walk in the bithorax complex has now been extended 215 kb through the right half of the complex, and lesions for over 40 mutations have been located on the DNA map. The mutations can be grouped in a series of phenotypic classes, one for each abdominal segment, although each mutation typically affects more than one segment. The mutant lesions of each class are clustered, and they are aligned on the chromosome in the order of the body segments that they affect. Complementation tests suggest interactions between widely spaced DNA regions; indeed, the right half cannot be split anywhere without some loss of function. Karch F F Weiffenbach B B Peifer M M Bender W W Duncan I I Celniker S S Crosby M M Lewis E B EB eng Journal Article

UNITED STATES Cell 0413066 0 DNA, Recombinant 9007-49-2 DNA IM Abdomen embryology Alleles Animal Cell Differentiation Chromosome Mapping Cloning, Molecular DNA analysis genetics DNA, Recombinant Drosophila melanogaster analysis embryology genetics Female Genes Genes, Dominant Genes, Regulator Genetic Complementation Test Male Morphogenesis Mutation Phenotype Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0054503 91359139 1909359 1991 10 08 1991 10 08 2000 12 18

0167-7063 7 4 1991 The distribution of transcripts of neurogenic genes in neurogenic mutants of Drosophila melanogaster. 241-52 The neurogenic genes of Drosophila melanogaster are required for correct separation of neural and epidermal progenitor cells during early embryogenesis. Results from genetic analyses indicate that the neurogenic genes are functionally related. We have studied the spatial distribution of RNA from the neurogenic genes D1, neu, and m4, m5, m7 and E(spl) [four genes of the Enhancer of split complex] in various neurogenic mutant embryos by in situ hybridization. An abnormal distribution of RNA from certain of the genes is found in neurogenic mutants, suggesting that at least some of the functional interactions inferred from genetic data take place at the transcriptional level. We discuss these results in relation to the events of early neurogenesis. Institut für Entwicklungsphysiologie, Universität zu Köln, Germany. Godt D D Schrons H H Guth S S Campos-Ortega J A JA eng Journal Article

ENGLAND J Neurogenet 8406473 IM Animal Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian physiology Enhancer Elements (Genetics) Gene Expression Genes Nervous System embryology Nucleic Acid Hybridization Support, Non-U.S. Gov't Transcription, Genetic FBrf0038059 83028506 6813190 1982 12 18 1982 12 18 2000 12 18

0016-6731 102 1 1982 Sep Polycomblike: a gene that appears to be required for the normal expression of the bithorax and antennapedia gene complexes of Drosophila melanogaster. 49-70 A newly identified gene is described that is required for the maintenance of normal identities in many of the body segments of the fly. The effects of mutants in this gene, which is called Polycomblike (Pcl), suggest that its wild-type allele functions in the regulation of the bithorax gene complex (BX-C) and the Antennapedia gene complex (ANT-C). Evidence in favor of this idea derives from (1) the close correspondence between segmental transformations caused by Pcl mutants and those caused by dominant gain-of-function mutants in the BX-C and ANT-C, (2) the interactions observed between Pcl mutants and mutants in these complexes, and (3) the dependence upon BX-C and ANT-C dosage of the severity of at least one of the transformations caused by Pcl mutants. Arguments are presented that the control of the BX-C and ANT-C by Pcl+ is negative in nature. The results of clonal analysis experiments indicate that, at least for the BX-C, Pcl+ exerts this control until late in development. Since the wild-type allele of another gene, called Polycomb (Pc), has previously been shown to have many of the same properties as Pcl+, it appears that the BX-C and perhaps also the ANT-C are continuously regulated during development by at least two and probably several other genes. Duncan I M IM eng HD 06331 HD NICHD Journal Article

UNITED STATES Genetics 0374636 IM Animal Drosophila melanogaster anatomy & histology genetics Genes, Structural Head anatomy & histology Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Thorax anatomy & histology FBrf0112048 20027408 10557109 1999 12 15 1999 12 15 2000 12 18

0950-9232 18 45 1999 Nov 1 Stress signaling in Drosophila. 6172-82 Cells commonly use multiprotein kinase cascades to signal information from the cell membrane to the nucleus. Several conserved signaling pathways related to the mitogen activated protein kinase (MAPK) pathway allow cells to respond to normal developmental signals as well as signals produced under stressful conditions. Genetic and molecular studies in Drosophila melanogaster over the last several years have related that components of stress signaling pathways, namely the Jun kinase (JNK) and p38 kinase signaling modules, are functionally conserved and participate in numerous processes during normal development. Specifically, the JNK pathway is required for morphogenetic movements in embryogenesis and generation of tissue polarity in the adult. The role of the p38 pathway in generation of axial polarity during oogenesis has been inferred from phenotypic analysis of mutations in the Drosophila homolog of DMKK3. In addition to their requirement for normal development, cell culture and genetic investigations point to a role for both the JNK and p38 pathways in regulation of the immune response in the fly. This review details the known components of stress signaling pathways in Drosophila and recent insights into how these pathways are used and regulated during development and homeostasis. Howard Hughes Medical Institute, Harvard Medical School, Department of Genetics, 200 Longwood Avenue, Boston, Massachusetts, MA 02115, USA. Stronach B E BE Perrimon N N eng Journal Article Review Review, Tutorial

ENGLAND Oncogene 8711562 0 MAP Kinase Signaling System 0 Membrane Proteins 0 Receptors, Tumor Necrosis Factor 0 notch protein EC 2.7.1.- JNK-activating protein kinase EC 2.7.1.37 Mitogen-Activated Protein Kinase Kinases EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- mitogen-activated protein kinase p38 EC 3.6.1.- GTP Phosphohydrolases IM Animal Body Patterning Drosophila melanogaster embryology enzymology genetics immunology GTP Phosphohydrolases metabolism Immunity physiology Intercellular Junctions metabolism MAP Kinase Signaling System Membrane Proteins metabolism Mitogen-Activated Protein Kinase Kinases genetics metabolism Mitogen-Activated Protein Kinases genetics metabolism Receptors, Tumor Necrosis Factor metabolism 86 FBrf0146986 21932428 11934863 2002 04 05 2002 06 13

0950-1991 129 8 2002 Apr Spitz/EGFr signalling via the Ras/MAPK pathway mediates the induction of bract cells in Drosophila legs. 1975-82 In the development of Drosophila, the activation of the EGFr pathway elicits different cellular responses at different times and in different tissues. A variety of approaches have been used to identify the mechanisms that confer this response specificity. We have analysed the specification of bract cells in Drosophila legs. We observed that mechanosensory bristles induced bract fate in neighbouring epidermal cells, and that the RAS/MAPK pathway mediated this induction. We have identified Spitz and EGFr as the ligand and the receptor of this signalling, and by ubiquitous expression of constitutively activated forms of components of the pathway we have found that the acquisition of bract fate is temporally and spatially restricted. We have also studied the role of the poxn gene in the inhibition of bract induction in chemosensory bristles. Centro de Biología Molecular Severo Ochoa-C.S.I.C., Facultad de Ciencias-CV, Universidad Autónoma-Cantoblanco, 28049 Madrid, Spain. del Alamo David D Terriente Javier J Díaz-Benjumea Fernando J FJ eng Journal Article

England Development 8701744 0 Eye Proteins 0 MAP Kinase Signaling System 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Transcription Factors 147037-52-3 pox neuro protein 147954-53-8 gil protein 148175-53-5 spitz protein EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 3.6.1.- ras Proteins IM Animal Drosophila melanogaster genetics metabolism Eye Proteins genetics Genes, Insect physiology MAP Kinase Signaling System Membrane Proteins genetics metabolism Mitogen-Activated Protein Kinases metabolism Nerve Tissue Proteins genetics Receptor, Epidermal Growth Factor genetics metabolism Support, Non-U.S. Gov't Transcription Factors genetics ras Proteins metabolism FBrf0036530 82051265 6795082 1982 01 09 1982 01 09 2000 12 18

0016-6731 97 3-4 1981 Mar-Apr Genetic and developmental analysis of a temperature-sensitive minute mutation of Drosophila melanogaster. 581-606 A temperature-sensitive (ts) third chromosome Minute (M) mutation, designated Q-III, has been recovered and characterized. Q-III heterozygotes raised at 29 degrees exhibit all of the dominant traits of M mutants including small bristles, rough eyes, prolonged development, reduced viability and interactions with several unrelated mutations. Q-III homozygotes raised at 29 degrees are lethal; death occurs primarily during the first larval instar. When raised at 22 degrees, Q-III heterozygotes are phenotypically normal and Q-III homozygotes display moderate M traits. In addition, Q-III elicits ts sterility and maternal-effect lethality. As is true of M lesions, the dominant traits of Q-III are not expressed in triploid females raised at 29 degrees. Complementation tests suggest that Q-III is a ts allele of M(3)LS4, which is located in 3L near the centromere.--Reciprocal temperature-shift experiments revealed that the temperature-sensitive period (TSP) of Q-III lethality is polyphasic, extending from the first instar to the latter half of pupation. Heat-pulse experiments further resolved this into two post-embryonic TSPs: one occurring during the latter half of the second larval instar, and the other extending from the larval/pupal boundary to the second half of pupation. In addition, heat pulses elicited a large number of striking adult phenotypes in Q-III individuals. These included pattern alterations such as deficiencies and duplications and other morphological defects in structures produced by the eye-antennal, leg, wing and genital imaginal discs and the abdominal histoblasts. Each defect or pattern alteration is associated with a specific TSP during development.--We favor the interpretation that most of the major Q-III defects, particularly the structural duplications and deficiencies, result from temperature-induced cell death in mitotically active imaginal anlagen, while the small macrochaete phene probably results from the direct effects of Q-III on bristle synthesis. The hypothesis that the Q-III locus specifies a component required for protein synthesis is discussed, and it is concluded that this hypothesis can account for the pleiotropy of Q-III, and that perhaps it can be extended to M loci in general. Sinclair D A DA Suzuki D T DT Grigliatti T A TA eng Journal Article

UNITED STATES Genetics 0374636 IM Animal Chromosomes ultrastructure Crosses, Genetic Drosophila melanogaster genetics Female Genes, Lethal Heterozygote Male Mutation Phenotype Support, Non-U.S. Gov't Temperature FBrf0160968 22668887 12783796 2003 06 04 2003 08 14

0950-1991 130 14 2003 Jul Wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila. 3259-68 Identifying the signals involved in maintaining stem cells is critical to understanding stem cell biology and to using stem cells in future regenerative medicine. In the Drosophila ovary, Hedgehog is the only known signal for maintaining somatic stem cells (SSCs). Here we report that Wingless (Wg) signaling is also essential for SSC maintenance in the Drosophila ovary. Wg is expressed in terminal filament and cap cells, a few cells away from SSCs. Downregulation of Wg signaling in SSCs through removal of positive regulators of Wg signaling, dishevelled and armadillo, results in rapid SSC loss. Constitutive Wg signaling in SSCs through the removal of its negative regulators, Axin and shaggy, also causes SSC loss. Also, constitutive wg signaling causes over-proliferation and abnormal differentiation of somatic follicle cells. This work demonstrates that wg signaling regulates SSC maintenance and that its constitutive signaling influences follicle cell proliferation and differentiation. In mammals, constitutive beta-catenin causes over-proliferation and abnormal differentiation of skin cells, resulting in skin cancer formation. Possibly, mechanisms regulating proliferation and differentiation of epithelial cells, including epithelial stem cells, is conserved from Drosophila to man. Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tgx@stowers-institute.org Song Xiaoqing X Xie Ting T eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Proto-Oncogene Proteins 117758-26-6 wingless protein, Drosophila IM Animal Cell Differentiation Cell Division Down-Regulation Drosophila Proteins metabolism physiology Drosophila melanogaster Female Gene Expression Regulation, Developmental Immunohistochemistry Microscopy, Fluorescence Models, Biological Mutation Ovary cytology metabolism Proto-Oncogene Proteins metabolism physiology Signal Transduction Stem Cells cytology Support, Non-U.S. Gov't FBrf0049801 90108679 2558050 1990 02 22 1990 02 22 2000 12 18

0890-9369 3 9 1989 Sep P-element-mediated enhancer detection: a versatile method to study development in Drosophila. 1288-300 We generated and characterized greater than 500 Drosophila strains that carry single copies of a novel P-element enhancer detector. In the majority of the strains, the beta-galactosidase reporter gene in the P-transposon responds to nearby transcriptional regulatory sequences in the genome. A remarkable diversity of spatially and temporally regulated staining patterns is observed in embryos carrying different insertions. We selected numerous strains as markers for different embryonic organs, tissues, and cells. Many of these strains should allow the study of complex developmental processes, such as nervous system development, which have not been convenient to analyze previously. Also, we present genetic evidence that some of the detected regulatory elements control nearby Drosophila genes. In light of our results, we discuss the diversity and complexity of cis-acting regulatory elements in the genome and the general applications of the enhancer detector method for the study of Drosophila development. Department of Cell Biology, Biozentrum, University of Basel, Switzerland. Bellen H J HJ O'Kane C J CJ Wilson C C Grossniklaus U U Pearson R K RK Gehring W J WJ eng Journal Article

UNITED STATES Genes Dev 8711660 0 Biological Markers 0 DNA Transposable Elements 0 Genetic Vectors 0 Recombinant Fusion Proteins EC 3.2.1.23 beta-Galactosidase IM Animal Biological Markers analysis DNA Transposable Elements Drosophila melanogaster embryology genetics Embryo, Nonmammalian analysis Enhancer Elements (Genetics) Gene Expression Regulation Genetic Vectors Recombinant Fusion Proteins analysis Support, Non-U.S. Gov't beta-Galactosidase analysis FBrf0128697 20296745 10835390 2000 09 08 2000 09 08 2002 11 01

0016-6731 155 2 2000 Jun Quantitative trait loci affecting components of wing shape in Drosophila melanogaster. 671-83 Two composite multiple regression-interval mapping analyses were performed to identify candidate quantitative trait loci (QTL) affecting components of wing shape in Drosophila melanogaster defined by eight relative warp-based measures. A recombinant inbred line design was used to map QTL for the shape of two intervein regions in the anterior compartment of the wing, using a high resolution map of retrotransposon insertion sites between Oregon-R and Russian 2b. A total of 35 QTL representing up to 23 different loci were identified, many of which are located near components of the epidermal growth factor-Ras signal transduction pathway that regulates vein vs. intervein decision making and vein placement. Over one-half of the loci were detected in both sexes, and just under one-half were detected at two different growth temperatures. Different loci were found to affect aspects of shape in each intervein region, confirming that the shape of the whole wing should be regarded as a compound trait composed of several developmental units. In addition, a reciprocal backcross design was used to map QTL affecting shape in the posterior compartment of the wings of 831 flies, using a molecular map of 16 allele-specific oligohybridization single nucleotide polymorphism (SNP) markers between two divergent inbred lines. A total of 13 QTL were detected and shown to have generally additive effects on separable components of shape, in both sexes. By contrast, 8 QTL that affected wing size in these backcrosses were nearly dominant in their effects. The results confirm at the genetic level that wing shape is regulated independent of wing size and set up the hypothesis that wing shape is regulated in part through the regulation of the length and positioning of wing veins, involving quantitative regulation of the activity of secreted growth factors. Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695-7614, USA. Zimmerman E E Palsson A A Gibson G G eng Journal Article

UNITED STATES Genetics 0374636 0 DNA Primers IM Animal Base Sequence DNA Primers Drosophila melanogaster genetics Quantitative Trait, Heritable Support, Non-U.S. Gov't Wing anatomy & histology FBrf0044891 87060317 3097291 1987 01 22 1987 01 22 2000 12 18

0167-7063 3 6 1986 Nov Role of the optic lobes in the regulation of the locomotor activity rhythm of Drosophila melanogaster: behavioral analysis of neural mutants. 321-43 The locomotor activity patterns of the Drosophila melanogaster brain mutants optomotor blind (omb), lobula plateless (lop), minibrain (mnb), small optic lobes (sol), sine oculis (so), and the double mutants mnb;so and sol;so, all of which show reductions in the optic lobes, were investigated and compared with those of the wild-type. In none of the mutants was the number of arrhythmic flies significantly higher than in the wild-type, indicating that the optic lobes are not the sole site of a pacemaker controlling the locomotor activity rhythm. However, these mutations greatly influence the stability of the circadian system, in that the number of flies simultaneously showing two or more circadian components increased as the optic lobe defects became more severe. In flies with the strongest reduction of the optic lobes, two free-running circadian components were found almost exclusively. This suggests a two-oscillator control of the locomotor activity. Eyeless mutants also expressing a neural mutation were entrained by light:dark (LD) cycles, but their activity pattern in LD was changed compared to the wild-type and the eyeless mutant so. Helfrich C C eng Journal Article

NETHERLANDS J Neurogenet 8406473 IM Animal Circadian Rhythm Drosophila melanogaster Female Heat Light Male Motor Activity physiology Mutation Optic Lobe physiology FBrf0049909 89232693 2497049 1989 06 19 1989 06 19 2000 12 18

0016-6731 121 3 1989 Mar The ash-1, ash-2 and trithorax genes of Drosophila melanogaster are functionally related. 517-25 Mutations in the ash-1 and ash-2 genes of Drosophila melanogaster cause a wide variety of homeotic transformations that are similar to the transformations caused by mutations in the trithorax gene. Based on this similar variety of transformations, it was hypothesized that these genes are members of a functionally related set. Three genetic tests were employed here to evaluate that hypothesis. The first test was to examine interactions of ash-1, ash-2 and trithorax mutations with each other. Double and triple heterozygotes of recessive lethal alleles express characteristic homeotic transformations. For example, double heterozygotes of a null allele of ash-1 and a deletion of trithorax have partial transformations of their first and third legs to second legs and of their halteres to wings. The penetrance of these transformations is reduced by a duplication of the bithorax complex. The second test was to examine interactions with a mutation in the female sterile (1) homeotic gene. The penetrance of the homeotic phenotype in progeny from mutant mothers is increased by heterozygosis for alleles of ash-1 or ash-2 as well as for trithorax alleles. The third test was to examine the interaction with a mutation of the Polycomb gene. The extra sex combs phenotype caused by heterozygosis for a deletion of Polycomb is suppressed by heterozygosis for ash-1, ash-2 or trithorax alleles. The fact that mutations in each of the three genes gave rise to similar results in all three tests represents substantial evidence that ash-1, ash-2 and trithorax are members of a functionally related set of genes. Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218. Shearn A A eng Journal Article

UNITED STATES Genetics 0374636 IM Alleles Animal Chromosome Deletion Crosses, Genetic Drosophila melanogaster genetics Genes Heterozygote Mutation Phenotype Support, U.S. Gov't, P.H.S. Transformation, Genetic FBrf0074210 94283089 8013251 1994 07 26 1994 07 26 2000 12 18

0009-5915 103 1 1994 Mar Polytene chromosomes of monogenic and amphogenic Chrysomya species (Calliphoridae, Diptera): analysis of banding patterns and in situ hybridization with Drosophila sex determining gene sequences. 16-30 Standard maps for the five banded polytene chromosomes found in trichogen cell nuclei of the monogenic blowfly Chrysomya rufifacies and the amphogenic Chrysomya pinguis are presented. The chromosomes are highly homologous in the two species; differences in banding patterns are predominantly caused by one pericentric and ten paracentric inversions. In chromosome 5 of the amphogenic Chrysomya phaonis, also analysed in this paper, an additional paracentric inversion was observed. The distribution of species specific inversions indicates that the monogenic C. rufifacies is phylogenetically older than the amphogenic species. The maternal sex realizer locus F'/f on polytene chromosome 5 of C. rufifacies is not associated with a structural heterozygosity. Chromosome pair 6 of C. rufifacies and the sex chromosome pair of C. pinguis are under-replicated in polytene nuclei; they consist of irregular chromatin granules, frequently associated with nucleolus material. Evolution of heteromorphic sex chromosomes in Chrysomya is probably correlated with heterochromatin accumulation. A search for sex determining genes in Chrysomya was initiated using sex determining sequences from Drosophila melanogaster for in situ hybridization. The polytene band 41A1 on chromosome 5 of monogenic and amphogenic Chrysomya species contains sequences homologous to the maternal sex determining gene daughterless (da). Homology to the zygotic gene Sex-lethal (Sxl) of Drosophila is detected in band 39A1 on chromosome 5 of C. rufifacies. The findings reported here are the first evidence for a possible homology between the da gene of Drosophila and the maternal sex realizer F' of C. rufifacies. An hypothesis for the evolution of the maternal effect sex determination of C. rufifacies is proposed. Zoologisches Institut, Universität Kiel, Germany. Puchalla S S eng Journal Article

GERMANY Chromosoma 2985138R IM Animal Chromosome Banding Diptera genetics Drosophila melanogaster genetics Female Genes, Insect In Situ Hybridization Male Phylogeny Sex Chromosomes Sex Determination (Analysis) Support, Non-U.S. Gov't FBrf0076038 95042724 7954795 1994 11 29 1994 11 29 2003 08 29

0092-8674 79 2 1994 Oct 21 The suppressor of hairless protein participates in notch receptor signaling. 273-82 In a genetic screen for mutations that attenuate Notch signaling in the developing Drosophila eye, we isolated rare, gain-of-function alleles of Suppressor of Hairless (Su(H)), the fly homolog of the mammalian C promoter-binding factor 1 (CBF1) gene. Su(H) exhibits numerous allele-specific genetic interactions with Notch as well as with Delta, deltex, and mastermind. In cultured Drosophila cells, the Su(H) protein is sequestered in the cytoplasm when coexpressed with Notch protein and is translocated to the nucleus when Notch binds to its ligand Delta. Cytoplasmic retention of Su(H) requires the intracellular cdc10/ankyrin repeats of Notch, which associate with Su(H) protein in the yeast interaction trap assay. These results indicate that Notch activity may regulate nuclear events by controlling the activity of a DNA-binding protein. Howard Hughes Medical Institute, Department of Biology, Yale University, New Haven, Connecticut 06536. Fortini M E ME Artavanis-Tsakonas S S eng NS26084 NS NINDS Journal Article

UNITED STATES Cell 0413066 0 Ankyrins 0 DNA-Binding Proteins 0 Fungal Proteins 0 Insect Hormones 0 Macromolecular Systems 0 Membrane Proteins 0 Nuclear Proteins 0 Repressor Proteins 0 cdc10+ protein 0 delta protein 0 deltex protein, Drosophila 0 notch protein 0 suppressor of Hairless protein, Drosophila IM Dx N Su(H) Amino Acid Sequence Animal Ankyrins chemistry Cell Compartmentation DNA-Binding Proteins physiology Drosophila melanogaster embryology physiology Fungal Proteins chemistry Genes, Structural, Insect Insect Hormones chemistry physiology Macromolecular Systems Membrane Proteins chemistry physiology Molecular Sequence Data Mutagenesis Nuclear Proteins physiology Protein Binding Repetitive Sequences, Nucleic Acid Repressor Proteins physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0092672 97178966 9053307 1997 03 13 1997 03 13 2002 10 21

0950-1991 124 2 1997 Jan Regulation of a dpp target gene in the Drosophila embryo. 303-11 In Drosophila, two TGF-beta growth factors, dpp and screw, function synergistically to subdivide the dorsal ectoderm into two embryonic tissues, the amnioserosa and dorsal epidermis. Previous studies have shown that peak dpp activity is required for the localized expression of zerknüllt (zen), which encodes a homeodomain transcription factor. We present evidence that zen directly activates the amnioserosa-specific expression of a downstream target gene, Race (Related to angiotensin converting enzyme). A 533 bp enhancer from the Race promoter region is shown to mediate selective expression in the amnioserosa, as well as the anterior and posterior midgut rudiments. This enhancer contains three zen protein binding sites, and mutations in these sites virtually abolish the expression of an otherwise normal Race-lacZ fusion gene in the amnioserosa, but not in the gut. Genetic epistasis experiments suggest that zen is not the sole activator of Race, although a hyperactivated form of zen (a zen-VP16 fusion protein) can partially complement reduced levels of dpp activity. These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa. Department of Biology, UCSD, La Jolla, CA 92093-0357, USA. Rusch J J Levine M M eng GM 46638 GM NIGMS Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Oligodeoxyribonucleotides 0 Recombinant Fusion Proteins 0 Repressor Proteins 0 SCW protein, Drosophila 0 Transcription Factors 0 Transforming Growth Factor beta 0 Zerknuellt homeodomain protein 0 dpp protein, Drosophila EC 3.2.1.23 beta-Galactosidase EC 3.4.15.- Race protein, Drosophila EC 3.4.15.1 Peptidyl-Dipeptidase A IM Animal Base Sequence Crosses, Genetic Drosophila melanogaster embryology genetics Ectoderm physiology Embryo, Nonmammalian physiology Enhancer Elements (Genetics) Female Gene Expression Regulation, Developmental Genes, Insect Insect Proteins biosynthesis metabolism Male Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides Peptidyl-Dipeptidase A biosynthesis Recombinant Fusion Proteins biosynthesis Repressor Proteins biosynthesis Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Transforming Growth Factor beta biosynthesis metabolism beta-Galactosidase biosynthesis FBrf0089731 96365474 8769651 1996 10 03 1996 10 03 2002 11 01

0890-9369 10 16 1996 Aug 15 Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer. 2089-101 The Drosophila doublesex female-specific splicing enhancer consists of two classes of regulatory elements, six 13-nucleotide repeat sequences, and a single purine-rich element (PRE). Here, we show that the Drosophila regulatory proteins Transformer (Tra) and Transformer 2 (Tra2) recruit different members of the SR family of splicing factors to the repeats and the PRE. The complexes formed on the repeats in HeLa cell extract consist of Tra, Tra2, and the SR protein 9G8. in Drosophila Kc cell extract, Tra and Tra2 recruit the SR protein RBP1 to the repeats. These proteins are arranged in a specific order on the repeats, with the SR protein at the 5' end of each repeat, and Tra2 at each 3' end. Although Tra did not cross-link strongly to the repeats, its presence was essential for the binding of Tra2 to the 3' end of the repeat. Individual SR proteins were also recruited to the PRE by Tra and Tra2, but in this case they were SF2/ASF and dSRp30 in HeLa and Drosophila cell extracts, respectively. The binding of Tra2, Tra, and the specific SR proteins to the repeats or the PRE was highly cooperative within each complex. Thus, Tra2, which contains a single RNA binding domain, can recognize distinct sequences in the repeats and the PRE in conjunction with specific SR proteins. These observations show that the protein composition of each complex is determined by the RNA recognition sequence and specific interactions between SR proteins and Tra and Tra2. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Lynch K W KW Maniatis T T eng Journal Article

UNITED STATES Genes Dev 8711660 0 Cross-Linking Reagents 0 DNA-Binding Proteins 0 Insect Hormones 0 Nuclear Proteins 0 RNA, Messenger 0 RNA-Binding Proteins 0 Ribonucleoproteins 0 SFRS7 protein, human 0 doublesex protein, Drosophila 0 transformer protein, Drosophila 0 transformer-2 protein IM Alternative Splicing Animal Cross-Linking Reagents DNA-Binding Proteins genetics Drosophila melanogaster genetics Female Gene Expression Regulation, Developmental Hela Cells Human Insect Hormones genetics Male Nuclear Proteins genetics RNA, Messenger genetics RNA-Binding Proteins genetics metabolism Regulatory Sequences, Nucleic Acid Ribonucleoproteins genetics FBrf0064490 93360989 8355700 1993 09 23 1993 09 23 2000 12 18

0270-7306 13 9 1993 Sep Multiple proteins interact with the fushi tarazu proximal enhancer. 5549-59 The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have taken a biochemical approach to identify DNA-binding proteins that regulate ftz gene expression through the proximal enhancer. DNase I footprinting and methylation interference experiments with staged Drosophila embryo nuclear extracts identified nine protein binding sites in the proximal enhancer. Ten different sequence-specific DNA-binding complexes that interact with eight of these sites were identified. Some interact with multiple sites, while others bind to single sites in the enhancer. Two of the complexes that interact with multiple sites appear to contain the previously described ftz regulators, FTZ-F1 and TTK/FTZ-F2. These in vitro studies allowed us to narrow down the proximal enhancer to a 323-bp DNA fragment that contains all of the protein binding sites. Expression directed by this minimal enhancer element in seven ftz-like stripes in transgenic embryos is identical to that directed by the full-length enhancer. Internal deletions of several sites abolish reporter gene expression in vivo. Thus, the ftz proximal enhancer, like other cell-type-specific eukaryotic enhancers, interacts with an array of proteins that are expected to mediate the establishment, maintenance, and repression of transcription of the ftz gene in seven stripes in the developing embryo. Brookdale Center for Molecular Biology, Mt. Sinai School of Medicine, New York, New York 10029. Han W W Yu Y Y Altan N N Pick L L eng HD 27937-01A1 HD NICHD Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA-Binding Proteins 0 Insect Hormones 0 Nuclear Proteins 0 Oligodeoxyribonucleotides 0 fushi tarazu protein 0 tramtrack protein IM ftz ttk Animal Base Sequence DNA Mutational Analysis DNA-Binding Proteins metabolism Drosophila melanogaster embryology genetics Enhancer Elements (Genetics) Gene Expression Regulation Insect Hormones genetics Molecular Sequence Data Morphogenesis Nuclear Proteins metabolism Oligodeoxyribonucleotides chemistry Restriction Mapping Structure-Activity Relationship Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zinc Fingers FBrf0151864 22182539 12194841 2002 08 26 2003 03 11 2003 06 16

0960-9822 12 16 2002 Aug 20 The fertile field of Drosophila Jak/STAT signalling. R569-75 The JAK/STAT pathway plays important roles in vertebrate and invertebrate development. The recent cloning and characterisation of the receptor in Drosophila shows that the pathway is conserved across phyla. In this review we describe current knowledge of the pathway and use genome data to discuss what elements are present in Drosophila. We also summarise recent work describing the involvement of the JAK/STAT pathway in oogenesis and spermatogenesis. Interestingly, the JAK/STAT pathway maintains the niche required for germline stem cell maintenance in the testis, providing the first molecular characterisation of a stem cell niche. Drosophila's streamlined pathway offers a simple model to find new elements and analyse the function of existing ones. Department of Zoology, Downing Street, University of Cambridge, CB2 3EJ, Cambridge, UK. jec24@cam.ac.uk Hombría James Castelli- Gair JC Brown Stephen S eng Journal Article Review Review, Tutorial

England Curr Biol 9107782 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Interleukin-6 0 Receptors, Interleukin 0 Trans-Activators 0 domeless protein, Drosophila 0 gamma-activated factor, 91-kD EC 2.7.1.- Janus kinase 1 EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster genetics physiology Female Interleukin-6 genetics metabolism Male Models, Biological Oogenesis physiology Ovary cytology physiology Protein Structure, Tertiary Protein-Tyrosine Kinase genetics metabolism Receptors, Interleukin metabolism Signal Transduction physiology Spermatogenesis physiology Stem Cells physiology Support, Non-U.S. Gov't Trans-Activators genetics metabolism 54 FBrf0051573 90382257 2119289 1990 10 24 1990 10 24 2000 12 18

0950-1991 109 2 1990 Jun Localization of vasa, a component of Drosophila polar granules, in maternal-effect mutants that alter embryonic anteroposterior polarity. 425-33 Cytoplasm at the posterior pole of the early Drosophila embryo, known as polar plasm, serves as a source of information necessary for germ cell determination and for specification of the abdominal region. Likely candidates for cytoplasmic elements important in one or both of these processes are polar granules, organelles concentrated in the cortical cytoplasm of the posterior pole. Females homozygous for any one of the maternal-effect mutations, tudor, oskar, staufen, vasa, or valois give rise to embryos that lack localized polar granules, fail to form the germ cell lineage and have abdominal segment deletions. Using antibodies against a polar granule component, the vasa protein, we find that vasa synthesis or localization is affected by these mutations. In vasa mutants, synthesis of vasa protein is absent or severely restricted. In oskar and staufen mutant females, vasa synthesis appears normal, but the vasa protein is not localized. In tudor and valois mutant females, vasa is localized to the posterior pole of oocytes, but this localization is lost following egg activation. In addition to the posterior localized vasa, there is a low level of vasa distributed throughout the embryo. A function for this distributed vasa is postulated based on the observation that embryos from Bicaudal-D mothers, in which abdominal determinants are incorrectly localized to the anterior pole, do not show any ectopic vasa localization, though abdomen development at the anterior end depends on the amount of vasa protein in the embryo. Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143. Hay B B Jan L Y LY Jan Y N YN eng Journal Article

ENGLAND Development 8701744 0 Proteins IM Animal Cytoplasm physiology Drosophila melanogaster physiology Embryo, Nonmammalian chemistry Female Genes physiology Immunohistochemistry Mutation Oocytes chemistry Oogenesis genetics Proteins analysis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0079850 95237203 7720712 1995 05 22 1995 05 22 2002 09 23

0261-4189 14 6 1995 Mar 15 Three protein binding sites form an enhancer that regulates sex- and fat body-specific transcription of Drosophila yolk protein genes. 1221-30 Transcription of the Drosophila yolk protein (Yp) genes is regulated by the somatic sex determination pathway. A gene at the bottom of this pathway, doublesex, encodes the female-specific DSXF and male-specific DSXM proteins that bind to and regulate transcription from several sites in the Yp genes. We report site-directed mutagenesis, protein binding and germline transformation experiments that identify and characterize the activity of a single binding site (dsxA) for the doublesex proteins and two binding sites for other regulatory proteins. A single copy of the three sites is sufficient to direct the sex and fat body specificities of Yp transcription. The sites form an enhancer with two strongly synergistic enhancer elements. One element (22 bp) consists of dsxA and an overlapping site, bzip1, that binds the DmC/EBP (slbo) protein, a member of the bZIP family of transcriptional activators. The other element is an 11 bp binding site (ref1) for an unknown protein. Tissue-specific activation requires strong cooperation between the ref1 site and the bzip1 or dsxA sites. Sex specificity is regulated exclusively by the dsxA site which connects the sex determination pathway to the target gene through DSXM repression and DSXF activation. Department of Biochemistry, Brandeis University, Waltham, MA 02254-9110, USA. An W W Wensink P C PC eng GM21626 GM NIGMS GM46327 GM NIGMS Journal Article

ENGLAND EMBO J 8208664 0 DNA-Binding Proteins 0 Egg Proteins 0 Insect Hormones 0 Repressor Proteins 0 Transcription Factors 0 doublesex protein, Drosophila 148997-45-9 slow border cells protein 9007-49-2 DNA IM Animal Base Sequence Binding Sites DNA genetics DNA-Binding Proteins metabolism Drosophila melanogaster genetics Egg Proteins genetics Enhancer Elements (Genetics) genetics Fat Body physiology Female Gene Expression Regulation, Developmental physiology Genes, Insect genetics Germ-Line Mutation physiology Insect Hormones metabolism Male Molecular Sequence Data Repressor Proteins metabolism Sex Differentiation genetics Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Transcription, Genetic genetics FBrf0155467 22350133 12447387 2002 12 03 2003 01 09

1465-7392 4 12 2002 Dec Pointed and Tramtrack69 establish an EGFR-dependent transcriptional switch to regulate mitosis. 976-80 Cell division in animals must be regulated; during development, for example, proliferation often occurs in spatially and temporally restricted patterns, and loss of mitotic control underlies cancer. The epidermal growth factor receptor (EGFR) has been implicated extensively in the control of cell proliferation in metazoans; in addition, hyperactivity of the EGFR and its three relatives, ErbB2-ErbB4, are implicated in many cancers. But little is known about how these receptor tyrosine kinases regulate the cell cycle. In the developing Drosophila melanogaster imaginal eye disc, there is a single patterned mitosis that sweeps across the eye disc epithelium in the third larval instar. This 'second mitotic wave' is triggered by EGFR signalling and depends on expression of String, the Drosophila homologue of Cdc25 phosphatase, the ultimate regulator of mitosis in all eukaryotic cells. Here we show that two antagonistic transcriptional regulators, Pointed, an activator, and Tramtrack69, a repressor, directly regulate the transcription of string. The activity of at least one of these regulators, Pointed, is controlled by EGFR signalling. This establishes a molecular mechanism for how intercellular signalling can control string expression, and thereby cell proliferation. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. Baonza Antonio A Murawsky Christopher M CM Travers Andrew A AA Freeman Matthew M eng Journal Article

England Nat Cell Biol 100890575 0 Proto-Oncogene Proteins 0 Repressor Proteins 0 pointed protein 0 string protein, Drosophila 0 tramtrack protein EC 3.1.3.16 Phosphoprotein Phosphatase IM Animal Drosophila melanogaster embryology genetics Eye cytology embryology Gene Expression Regulation Genes, erbB-1 Mitosis genetics Phosphoprotein Phosphatase genetics Proto-Oncogene Proteins genetics Repressor Proteins genetics Signal Transduction genetics Support, Non-U.S. Gov't Transcription, Genetic FBrf0160973 22719041 12835389 2003 07 01 2003 09 30

0950-1991 130 16 2003 Aug Echinoid is essential for regulation of Egfr signaling and R8 formation during Drosophila eye development. 3725-33 Precisely regulated Egfr activity is essential for normal development and cell differentiation. We demonstrate that the transmembrane protein Echinoid is required to downregulate Egfr activity in the developing Drosophila eye, ensuring a normal array of R8 photoreceptor neurons. Echinoid is an L1-type transmembrane molecule that is expressed in all cells of the eye imaginal discs and, unlike many other Egfr inhibitors, does not appear to be regulated transcriptionally. Echinoid co-precipitates with Egfr from cultured cells and eye imaginal discs, and Egfr activity promotes tyrosine phosphorylation of Echinoid. These observations suggest that Echinoid inhibits Egfr through direct interactions. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St Louis, MO 63110, USA. Spencer Susan A SA Cagan Ross L RL eng R01 CA 84309 CA NCI Journal Article

England Development 8701744 0 Cell Adhesion Molecules 0 DNA-Binding Proteins 0 Drosophila Proteins 0 ED protein, Drosophila 0 Eye Proteins 0 Nerve Tissue Proteins 0 Repressor Proteins 0 ato protein 0 echinoid protein, Drosophila 147954-53-8 gil protein EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.10.- ERK-A protein IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase metabolism Cell Adhesion Molecules genetics metabolism Cells, Cultured DNA-Binding Proteins metabolism Down-Regulation Drosophila Proteins genetics metabolism Drosophila melanogaster anatomy & histology growth & development Enzyme Activation Eye Proteins genetics metabolism Gene Expression Regulation, Developmental Morphogenesis Nerve Tissue Proteins genetics metabolism Neurons cytology physiology Phosphorylation Photoreceptors, Invertebrate growth & development metabolism ultrastructure Receptor, Epidermal Growth Factor genetics metabolism Repressor Proteins genetics metabolism Signal Transduction physiology Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0050687 91175683 2577346 1991 04 29 1991 04 29 2002 11 01

1043-4674 1 1 1989 Oct Mouse versions of fly developmental control genes: legitimate or illegitimate relatives? 9-18 Embryo development requires a complex order of events that must occur at the correct time and in the correct space. A series of decisions takes place as cells divide and become committed to increasingly specialized and limited domains of the embryo. Many genes that are important in orchestrating this process were originally identified in the fruitfly Drosophila melanogaster. Conserved sequences from the fly genes have been used to clone homologous genes in vertebrates, including mice. Studies of the pattern of expression of these genes during murine development in conjunction with the use of new functional assays suggest that not only DNA sequences, but also functional roles during embryogenesis, have been conserved. Thus, we may have the tools in hand to begin to understand how vertebrate development and cell differentiation take place. Department of Molecular Cell Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, FRG. Lobe C G CG Gruss P P eng Journal Article Review Review, Tutorial

UNITED STATES New Biol 9000976 0 Transcription Factors IM Antp Cdx-1 En-1 En-2 Hb Hox-1 Hox-1.2 Hox-1.3 Hox-1.4 Hox-1.5 Hox-1.6 Hox-2 Hox-2.1 Kr Krox-20 Pax-1 Zfp2 bcd cad gsb-d gsb-p kni Animal Cell Differentiation Cell Division Comparative Study Drosophila melanogaster embryology genetics Embryo and Fetal Development genetics Embryo, Nonmammalian anatomy & histology Gene Expression Regulation Genes, Homeobox Genes, Regulator Mice embryology genetics Models, Genetic Sequence Homology, Nucleic Acid Species Specificity Support, Non-U.S. Gov't Transcription Factors genetics Zinc Fingers genetics Zygote metabolism 65 FBrf0151822 22310829 12424525 2002 11 08 2003 06 30

0009-5915 111 4 2002 Nov The actin loci in the genus Drosophila: establishment of chromosomal homologies among five nearctic species of the Drosophila obscura group by in situ hybridization. 256-66 The actin genes of five nearctic species of the Drosophila obscura group were mapped by in situ hybridization, using the 5C actin gene of D. melanogaster as a probe. In all species but D. azteca eight actin loci were observed variously dispersed over all five (A- E) chromosomal elements. In D. azteca ten actin hybridization sites were found; four of which most probably originated by duplications or by transposition events. Although the five nearctic species differ from all other Drosophila species of the D. obscura group so far studied in the number of loci as well as in the chromosomal distribution and location of the actin loci, the uniformity of the main pattern with six actin loci throughout the genus Drosophila reinforces the hypothesis that the chromosomal elements have maintained their essential identities during the course of evolution. Our findings are in accordance with the conclusion that the nearctic D. obscura species have differentiated from a common ancestor of the palearctic species and that they belong to two distinct subgroups, the pseudoobscura and the affinis subgroups. Department of Genetics, Agricultural University of Athens, Greece. Bondinas George P GP Loukas Michael G MG Goulielmos George N GN Sperlich Diether D eng Journal Article 2002 09 06

Germany Chromosoma 2985138R 0 Actins IM Actins genetics Animal Chromosome Mapping Chromosomes Drosophila classification genetics In Situ Hybridization methods Phylogeny Salivary Glands FBrf0131303 20519447 11063688 2000 11 21 2001 01 04 2001 11 02

0016-6731 156 3 2000 Nov The necrotic gene in Drosophila corresponds to one of a cluster of three serpin transcripts mapping at 43A1.2. 1117-27 Mutants of the necrotic (nec) gene in Drosophila melanogaster die in the late pupal stage as pharate adults, or hatch as weak, but relatively normal-looking, flies. Adults develop black melanized spots on the body and leg joints, the abdomen swells with hemolymph, and flies die within 3 or 4 days of eclosion. The TOLL-mediated immune response to fungal infections is constitutively activated in nec mutants and pleiotropic phenotypes include melanization and cellular necrosis. These changes are consistent with activation of one or more proteolytic cascades. The nec gene corresponds to Spn43Ac, one of a cluster of three putative serine proteinase inhibitors at 43A1.2, on the right arm of chromosome 2. Although serpins have been implicated in the activation of many diverse pathways, lack of an individual serpin rarely causes a detectable phenotype. Absence of Spn43Ac, however, gives a clear phenotype, which will allow a mutational analysis of critical features of the molecular structure of serpins. Department of Genetics, University of Cambridge, Cambridge CB2 3EH, England. Green C C Levashina E E McKimmie C C Dafforn T T Reichhart J M JM Gubb D D eng GENBANK AJ245442 AJ245443 AJ245444 Journal Article

UNITED STATES Genetics 0374636 0 Recombinant Proteins 0 Serpins 0 Spn43ac protein IM Amino Acid Sequence Animal Animals, Genetically Modified Chromosome Mapping Cloning, Molecular Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Models, Molecular Molecular Sequence Data Multigene Family Necrosis Phenotype Protein Structure, Secondary Pupa Recombinant Proteins chemistry metabolism Sequence Alignment Sequence Deletion Sequence Homology, Amino Acid Serpins chemistry genetics Support, Non-U.S. Gov't Transcription, Genetic FBrf0134581 21098966 11171404 2001 02 22 2001 04 12

0950-1991 128 5 2001 Mar Transcriptional regulation of cytoskeletal functions and segmentation by a novel maternal pair-rule gene, lilliputian. 801-13 Transcriptional control during early Drosophila development is governed by maternal and zygotic factors. We have identified a novel maternal transcriptional regulator gene, lilliputian (lilli), which contains an HMG1 (AT-hook) motif and a domain with similarity to the human fragile X mental retardation FMR2 protein and the AF4 proto-oncoprotein. Embryos lacking maternal lilli expression show specific defects in the establishment of a functional cytoskeleton during cellularization, and exhibit a pair-rule segmentation phenotype. These mutant phenotypes correlate with markedly reduced expression of the early zygotic genes serendipity alpha, fushi tarazu and huckebein, which are essential for cellularization and embryonic patterning. In addition, loss of lilli in adult photoreceptor and bristle cells results in a significant decrease in cell size. Our results indicate that lilli represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, California 94720-3200, USA. amy_tang@uclink4.berkeley.edu Tang A H AH Neufeld T P TP Rubin G M GM Müller H A HA eng GENBANK AF289034 Journal Article

England Development 8701744 0 Actins 0 DNA-Binding Proteins 0 Hkb protein 0 Homeodomain Proteins 0 Membrane Proteins 0 Nuclear Proteins 0 RNA, Messenger 0 Sry alpha protein 0 fushi tarazu protein 0 lilliputian protein, Drosophila IM Actins metabolism Amino Acid Sequence Animal Body Patterning Cell Size Cytoskeleton genetics metabolism DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics Embryo, Nonmammalian cytology physiology Female Flow Cytometry Gene Expression Regulation, Developmental Genes, Insect Genes, Reporter genetics Homeodomain Proteins genetics metabolism Human In Situ Hybridization Male Membrane Proteins genetics metabolism Microscopy, Confocal Microscopy, Fluorescence Microscopy, Video Microtubules metabolism Molecular Sequence Data Nuclear Proteins chemistry genetics metabolism Photoreceptors, Invertebrate cytology embryology metabolism RNA, Messenger metabolism Sequence Alignment Support, Non-U.S. Gov't Wing anatomy & histology FBrf0082190 95362019 7635286 1995 09 13 1995 09 13 2000 12 18

0016-6731 140 1 1995 May fs (1) Yb is required for ovary follicle cell differentiation in Drosophila melanogaster and has genetic interactions with the Notch group of neurogenic genes. 207-17 Phenotypic and genetic analyses demonstrate that fs (1) Yb activity is required in the soma for the development of a subset of ovarian follicle cells and to support later stages of egg maturation. Mutations in fs (1) Yb cause a range of ovarian phenotypes, from the improper segregation of egg chambers to abnormal dorsal appendage formation. The mutant phenotypes associated with fs (1) Yb are very similar to the ovarian aberrations produced by temperature-sensitive alleles of Notch and Delta. Possible functional or regulatory interactions between fs (1) Yb and Notch are suggested by genetic studies. A duplication of the Notch locus partially suppresses the female-sterility caused by fs (1) Yb mutations, while reducing Notch dosage makes the fs (1) Yb mutant phenotype more severe. In addition, fs (1) Yb alleles also interact with genes that are known to act with or regulate Notch activity, including Delta, daughterless, and mastermind. However, differences between the mutant ovarian phenotype of fs (1) Yb and that of Notch or Delta indicate that the genes do not have completely overlapping functions in the ovary. We propose that fs (1) Yb acts as an ovary-specific factor that determines follicle cell fate. Genetics Program, University of Iowa, Iowa City 52242, USA. Johnson E E Wayne S S Nagoshi R R eng GM-45843 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Hormones 0 Membrane Proteins 0 delta protein 0 notch protein IM Dl fs(1)Yb Alleles Animal Drosophila melanogaster genetics physiology Female Genes, Structural, Insect Infertility, Female genetics Insect Hormones genetics physiology Membrane Proteins genetics physiology Multigene Family Oogenesis Organ Specificity Ovarian Follicle Ovary growth & development ultrastructure Support, U.S. Gov't, P.H.S. FBrf0100221 98105082 9442871 1998 02 13 1998 02 13 2000 12 18

1081-0706 13 1997 Genetic analysis of the actin cytoskeleton in the Drosophila ovary. 147-70 The Drosophila ovary provides a favorable model system in which to study cellular morphogenesis. The development of a mature egg involves a syncytium of 16 germline cells and over 1000 somatically derived follicle cells. Intercellular transport, stable intercellular bridges, cell migrations, cell shape changes, and specific subcellular localization of many embryonic patterning determinants contribute to egg development and require a dynamic cytoskeleton. We discuss many of the recent genetic and cell biological studies that have led to insights into how the actin cytoskeleton is assembled and regulated during the morphogenesis of the Drosophila egg. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA. Robinson D N DN Cooley L L eng Journal Article Review Review, Academic

UNITED STATES Annu Rev Cell Dev Biol 9600627 0 Actins IM Actins chemistry genetics Animal Biological Transport Cell Adhesion Cytoskeleton chemistry metabolism Drosophila melanogaster genetics Female Oogenesis Ovary ultrastructure Support, U.S. Gov't, P.H.S. 109 FBrf0136861 21280809 11387220 2001 06 01 2001 07 05 2002 04 19

0261-4189 20 11 2001 Jun 1 Requirement of Hsp90 for centrosomal function reflects its regulation of Polo kinase stability. 2878-84 We have previously shown that the molecular chaperone heat shock protein 90 (Hsp90) is required to ensure proper centrosome function in Drosophila and vertebrate cells. This observation led to the hypothesis that this chaperone could be required for the stability of one or more centrosomal proteins. We have found that one of these is Polo, a protein kinase known to regulate several aspects of cell division including centrosome maturation and function. Inhibition of Hsp90 results in the inactivation of Polo kinase activity. It also leads to a loss in the ability of cytoplasmic extracts to complement the failure of salt-stripped preparations of centrosomes to nucleate microtubules. This effect can be rescued upon addition of active recombinant POLO: We also show that Polo and Hsp90 are part of a complex and conclude that stabilization of Polo is one of the mechanisms by which Hsp90 contributes to the maintenance of functional centrosomes. Cell Biology and Biophysics, and Gene Expression Programmes, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. de Cárcer G G do Carmo Avides M M Lallena M J MJ Glover D M DM González C C eng Journal Article

England EMBO J 8208664 0 Heat-Shock Proteins 90 0 Recombinant Proteins EC 2.7.1.- polo protein EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Cell Division Cell Line Centrosome physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Genetic Complementation Test Heat-Shock Proteins 90 metabolism Protein-Serine-Threonine Kinases chemistry metabolism Recombinant Proteins metabolism Support, Non-U.S. Gov't Vertebrates FBrf0056444 93016263 1383233 1992 11 25 1992 11 25 2001 11 02

0021-9525 119 3 1992 Nov Introns excised from the Delta primary transcript are localized near sites of Delta transcription. 503-12 Introns excised from the primary transcript of Delta (Dl), a Drosophila neurogenic gene, accumulate to unusually high levels in embryos. High resolution in situ hybridization reveals a striking localization of the excised introns to two foci per embryonic nucleus. The number of foci can be altered by varying the number of Dl genes present in the embryonic nucleus, suggesting that the excised introns are localized near sites of Dl transcription. This conclusion is supported by the observation that larval and imaginal disc nuclei containing two copies of Dl exhibit only one focus of intron accumulation, as expected for nuclei in which homologous chromosomes are paired. Interestingly, the excised introns do not appear to diffuse away from the foci until late prophase, at which time the foci disperse into numerous small dots of hybridization. These results suggest that the excised Dl introns may be associated with a structural element within the nucleus that is dissociated during cell division. Department of Biology, Indiana University, Bloomington 47405. Kopczynski C C CC Muskavitch M A MA eng GM33291 GM NIGMS Journal Article

UNITED STATES J Cell Biol 0375356 0 Oligodeoxyribonucleotides 63231-63-0 RNA IM DI Animal Base Sequence Cell Nucleus physiology Chromosomes physiology Drosophila melanogaster embryology genetics Embryo, Nonmammalian physiology Exons In Situ Hybridization Interphase Introns Mitosis Molecular Sequence Data Nervous System embryology Nervous System Physiology Oligodeoxyribonucleotides Polymerase Chain Reaction RNA genetics isolation & purification Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0077257 95062334 7972125 1994 12 27 1994 12 27 2000 12 18

0027-8424 91 24 1994 Nov 22 Identification of genes that interact with the sina gene in Drosophila eye development. 11689-93 The sina gene encodes a nuclear protein that is required for the correct development of R7 photoreceptor cells in the Drosophila eye. We conducted a genetic screen for mutations that reduce the activity of sina and found mutations that define nine genes whose products may be required for normal sina activity. Three of these genes also appear to be essential for signaling by the Sevenless-Ras pathway in R7 cells, of which one gene corresponds to the rolled locus (rl). The rl gene is known to encode a mitogen-activated protein kinase necessary for signaling by Ras. These results suggest that the products of these three genes may participate in a signaling pathway involving both Ras and Sina, possibly by functionally linking these two proteins. Howard Hughes Medical Institute, University of California, Berkeley 94720-3200. Carthew R W RW Neufeld T P TP Rubin G M GM eng 1R01EY10111-01 EY NEI Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Eye Proteins 0 Nuclear Proteins 0 seven in absentia protein EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 3.6.1.- ras Proteins IM Ras1 rl sina Animal Ca(2+)-Calmodulin Dependent Protein Kinase physiology Drosophila melanogaster genetics growth & development Eye growth & development Eye Proteins physiology Genes, Structural, Insect Nuclear Proteins physiology Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. ras Proteins physiology FBrf0032821 80090076 117907 1980 03 17 1980 03 17 2000 12 18

0092-8674 18 4 1979 Dec Studies of cloned sequences from four Drosophila heat shock loci. 1359-70 DNA cloned from the D. melanogaster (Oregon R) heat shock loci at 63BC and 95D codes for the 83,000 and the 68,000 dalton heat shock proteins, respectively. Both coding sequences occur once per haploid genome. Sequences complementary to messenger RNA for the 70,000 dalton heat shock protein are represented five times, twice at 87A and three times at 87 C. The copies at 87A differ characteristically from those at 87C in an interval of a few hundred bp near the 5' end of the messenger sequence, and the corresponding two classes of hsp 70 messenger RNA are found on polysomes after heat shock. Within this differential region, there is about 15% divergence between messenger sequences cloned from the two loci, while in the rest of the messenger region examined the homology is much closer although still imperfect. Unexpectedly, considerable homology is found between the sequence for the 68,000 dalton heat shock protein at 95D and the sequences for the 70,000 dalton protein at 87A and 87C, and between these sequences and a site in 87D. Messenger RNA molecules of 2.4, 2.55 and 3.05 kb code for the 68,000, 70,000 and 83,000 dalton heat shock proteins and hybridize to apparently uninterrupted DNA sequences of 2.1, 2.25 and 2.6 kb, respectively. Holmgren R R Livak K K Morimoto R R Freund R R Meselson M M eng Journal Article

UNITED STATES Cell 0413066 0 Proteins 0 RNA, Messenger 9007-49-2 DNA IM Animal Base Sequence Chromosome Mapping Chromosomes Cloning, Molecular DNA genetics Drosophila melanogaster genetics Genes, Structural Heat Proteins biosynthesis RNA, Messenger analysis genetics Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0123155 20054442 10585440 2000 01 13 2000 01 13 2000 12 18

0021-9258 274 50 1999 Dec 10 DFak56 is a novel Drosophila melanogaster focal adhesion kinase. 35621-9 The mammalian focal adhesion kinase (FAK) family of nonreceptor protein-tyrosine kinases have been implicated in controlling a multitude of cellular responses to the engagement of cell surface integrins and G protein-coupled receptors. We describe here a Drosophila melanogaster FAK homologue, DFak56, which maps to band 56D on the right arm of the second chromosome. Full-length DFak56 cDNA encodes a phosphoprotein of 140 kDa, which shares strong sequence similarity not only with mammalian p125(FAK) but also with the more recently described mammalian Pyk2 (also known as CAKbeta, RAFTK, FAK2, and CADTK) FAK family member. DFak56 has intrinsic tyrosine kinase activity and is phosphorylated on tyrosine in vivo. As is the case for FAK, tyrosine phosphorylation of DFak56 is increased upon plating Drosophila embryo cells on extracellular matrix proteins. In situ hybridization and immunofluorescence staining analysis showed that DFak56 is ubiquitously expressed with particularly high levels within the developing central nervous system. We utilized the UAS-GAL4 expression system to express DFak56 and analyze its function in vivo. Overexpression of DFak56 in the wing imaginal disc results in wing blistering in adults, a phenotype also observed with both position-specific integrin loss of function and position-specific integrin overexpression. Our results imply a role for DFak56 in adhesion-dependent signaling pathways in vivo during D. melanogaster development. Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, California 92037-1099, USA. Palmer R H RH Fessler L I LI Edeen P T PT Madigan S J SJ McKeown M M Hunter T T eng GENBANK AF112116 CA39780 CA NCI GM57689 GM NIGMS MH57460 MH NIMH Journal Article

UNITED STATES J Biol Chem 2985121R 0 Cell Adhesion Molecules 0 DNA, Complementary 0 Recombinant Proteins EC 2.7.1.- endogenous substrate pp120 EC 2.7.1.112 Protein-Tyrosine Kinase IM Amino Acid Sequence Animal Cell Adhesion Molecules chemistry genetics metabolism Chromosome Mapping DNA, Complementary Drosophila melanogaster enzymology genetics growth & development Embryo, Nonmammalian Evolution, Molecular Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Larva Mammals Molecular Sequence Data Molecular Weight Phylogeny Protein-Tyrosine Kinase chemistry genetics metabolism Pupa Recombinant Proteins chemistry metabolism Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. src Homology Domains FBrf0074370 94299023 8026629 1994 08 11 1994 08 11 2000 12 18

0012-1606 164 1 1994 Jul The function of argos in regulating cell fate decisions during Drosophila eye and wing vein development. 267-76 The Drosophila argos gene, which encodes a secreted protein with an EGF motif, is involved in several developmental processes regulating cell-cell interactions such as eye morphogenesis. Loss-of-function mutations in the argos gene cause an increase in the number of photoreceptor cells and cone cells, impaired retinal projections to the optic lobe, and the formation of extra veins. We show here that ubiquitously expressed argos product restored all these loss-of-function phenotypes. Overexpression of argos in the wild-type background resulted in the reduced number of photoreceptor cells, cone cells, and pigment cells, which are phenotypes opposite to those of the loss-of-function mutants. The argos gene is expressed in developing wing veins. Ubiquitous argos expression caused loss of veins in a dose-dependent manner. This phenotype was enhanced by the loss-of-function rhomboid mutation, implying the possibility that argos and rhomboid play key roles in a common pathway for normal wing vein formation. We propose that argos acts as an inhibitory signal for cellular differentiation in the developing eye and wing. Department of Molecular Neurobiology, University of Tokyo, Japan. Sawamoto K K Okano H H Kobayakawa Y Y Hayashi S S Mikoshiba K K Tanimura T T eng Journal Article

UNITED STATES Dev Biol 0372762 0 DNA, Complementary IM argos Animal Cell Communication Cell Differentiation DNA, Complementary genetics Drosophila melanogaster embryology genetics Eye embryology Gene Expression Support, Non-U.S. Gov't Wing embryology FBrf0057558 92390395 1518835 1992 10 07 1992 10 07 2000 12 18

0027-8424 89 17 1992 Sep 1 Binding of the Drosophila transformer and transformer-2 proteins to the regulatory elements of doublesex primary transcript for sex-specific RNA processing. 8092-6 Sex-specific alternative processing of double-sex (dsx) precursor messenger RNA (pre-mRNA) is one of the key steps that regulates somatic sexual differentiation in Drosophila melanogaster. By transfection analyses using dsx minigene constructs, we identified six copies of the 13-nucleotide sequences TC(T/A)(T/A)C(A/G)ATCAACA in the female-specific fourth exon that act as the cis elements for the female-specific splicing of dsx pre-mRNA. UV-crosslinking experiments revealed that both female-specific transformer (tra) and transformer-2 (tra-2) products bind to the 13-nucleotide sequences of dsx pre-mRNA. These results strongly suggest that the female-specific splicing of dsx pre-mRNA is activated by binding of these proteins to the 13-nucleotide sequences. Department of Biophysics, Faculty of Science, Kyoto University, Japan. Inoue K K Hoshijima K K Higuchi I I Sakamoto H H Shimura Y Y eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 Nucleic Acid Precursors 0 Oligodeoxyribonucleotides 0 RNA, Messenger 0 RNA-Binding Proteins 0 Ribonucleoproteins 0 transformer-2 protein IM dsx tra tra-2 Animal Base Sequence Drosophila melanogaster genetics Female Gene Expression Regulation Male Molecular Sequence Data Nucleic Acid Precursors metabolism Oligodeoxyribonucleotides chemistry RNA Splicing RNA, Messenger genetics RNA-Binding Proteins genetics Regulatory Sequences, Nucleic Acid Ribonucleoproteins metabolism Sex Differentiation Support, Non-U.S. Gov't Transfection FBrf0090589 96360335 8719770 1996 10 25 1996 10 25 2000 12 18

0167-7063 10 3 1995 Dec Distinct mechanisms of action of the Lozenge locus in Drosophila eye and antennal development are suggested by the analysis of dominant enhancers. 137-51 The development of the olfactory sense organs on the antenna of the fruit fly Drosophila utilises mechanisms distinct from those used in the rest of the adult peripheral nervous system. Lozenge (lz) is the only locus hither-to identified as required for the development of antennal sense organs. In addition to effects on the antenna, mutations in lz also affect the development of the eye and maxillary palp. We have used the readily-scored eye-phenotype in a temperature sensitive lz allele to screen for dominant modifiers of phenotypes at this locus. We analyse the phenotypes of both intragenic and extragenic modifiers. Our results reinforce the view from developmental studies that lz functions in eye and antennal development in distinct ways. Molecular Biology Unit, Tata Institute of Fundamental Research, Bombay, India. Gupta B P BP Rodrigues V V eng Journal Article

ENGLAND J Neurogenet 8406473 IM Alleles Animal Cell Lineage Drosophila melanogaster genetics growth & development Embryonic Induction Enhancer Elements (Genetics) Epistasis, Genetic Eye growth & development Gene Expression Regulation, Developmental Genes, Insect Genes, Regulator Mouth growth & development Mutagenesis Olfactory Pathways growth & development Phenotype Sense Organs growth & development Support, Non-U.S. Gov't FBrf0103055 98274203 9609827 1998 08 06 1998 08 06 2003 06 16

0950-1991 125 13 1998 Jul Recruitment of Tube and Pelle to signaling sites at the surface of the Drosophila embryo. 2443-50 A signaling pathway initiated by activation of the transmembrane receptor Toll defines dorsoventral polarity in the Drosophila embryo. Toll, which is present over the entire surface of the embryo, is activated ventrally by interaction with a spatially restricted, extracellular ligand. Tube and Pelle then transduce the signal from activated Toll to a complex of Dorsal and Cactus. Here we demonstrate by an mRNA microinjection assay that targeting of either Tube or Pelle to the plasma membrane by myristylation is sufficient to activate the signal transduction pathway that leads to Dorsal nuclear translocation. Using confocal immunofluorescence microscopy we also show that activated Toll induces a localized recruitment of Tube and Pelle to the plasma membrane. Together, these results strongly support the hypothesis that intracellular signaling requires the Toll-mediated formation of a membrane-associated complex containing both Tube and Pelle. Department of Molecular Biology and Oncology, UT Southwestern Medical Center, Dallas, Texas, USA. Towb P P Galindo R L RL Wasserman S A SA eng Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 RNA, Messenger 0 tube protein, Drosophila 544-63-8 Myristic Acid EC 2.7.1.- pelle protein EC 2.7.1.37 Protein-Serine-Threonine Kinases IM Animal Animals, Genetically Modified Body Patterning Cell Membrane metabolism Drosophila melanogaster embryology Embryo, Nonmammalian cytology physiology Insect Proteins biosynthesis physiology Microinjections Myristic Acid metabolism Protein-Serine-Threonine Kinases biosynthesis physiology RNA, Messenger metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0068416 94208532 8157002 1994 05 17 1994 05 17 2001 03 23

0261-4189 13 7 1994 Apr 1 The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway. 1628-35 Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the sevenless (Sev) RTK is required for development of the R7 photoreceptor cell. Components of the signal transduction pathway activated by Sev in the R7 precursor include proteins encoded by the gap1, drk, Sos, ras1 and raf loci. In this report we present evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and is required downstream of raf in the Sev signal transduction pathway. Howard Hughes Medical Institute, UCLA School of Medicine. Biggs W H WH 3rd Zavitz K H KH Dickson B B van der Straten A A Brunner D D Hafen E E Zipursky S L SL eng Journal Article

ENGLAND EMBO J 8208664 0 Eye Proteins 0 Membrane Glycoproteins 0 Proto-Oncogene Proteins 0 sevenless protein EC 2.7.1.112 Receptor Protein-Tyrosine Kinases EC 2.7.1.123 Ca(2+)-Calmodulin Dependent Protein Kinase EC 2.7.1.37 Proto-Oncogene Proteins c-raf EC 2.7.10.- ERK-A protein IM Animal Ca(2+)-Calmodulin Dependent Protein Kinase physiology DNA Mutational Analysis Drosophila embryology genetics Eye embryology ultrastructure Eye Proteins physiology Genetic Complementation Test Membrane Glycoproteins physiology Models, Biological Proto-Oncogene Proteins genetics Proto-Oncogene Proteins c-raf Receptor Protein-Tyrosine Kinases metabolism Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic FBrf0081900 95247821 7730407 1995 05 31 1995 05 31 2000 12 18

0021-9525 129 3 1995 May The Drosophila cell cycle gene fizzy is required for normal degradation of cyclins A and B during mitosis and has homology to the CDC20 gene of Saccharomyces cerevisiae. 725-37 The Drosophila cell cycle gene fizzy (fzy) is required for normal execution of the metaphase-anaphase transition. We have cloned fzy, and confirmed this by P-element mediated germline transformation rescue. Sequence analysis predicts that fzy encodes a protein of 526 amino acids, the carboxy half of which has significant homology to the Saccharomyces cerevisiae cell cycle gene CDC20. A monoclonal antibody against fzy detects a single protein of the expected size, 59 kD, in embryonic extracts. In early embryos fzy is expressed in all proliferating tissues; in late embryos fzy expression declines in a tissue-specific manner correlated with cessation of cell division. During interphase fzy protein is present in the cytoplasm; while in mitosis fzy becomes ubiquitously distributed throughout the cell except for the area occupied by the chromosomes. The metaphase arrest phenotype caused by fzy mutations is associated with failure to degrade both mitotic cyclins A and B, and an enrichment of spindle microtubules at the expense of astral microtubules. Our data suggest that fzy function is required for normal cell cycle-regulated proteolysis that is necessary for successful progress through mitosis. Department of Cell Biology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-0812, USA. Dawson I A IA Roth S S Artavanis-Tsakonas S S eng GENBANK U22419 NS26084 NS NINDS Journal Article

UNITED STATES J Cell Biol 0375356 0 Cdc20 protein 0 Cell Cycle Proteins 0 Cyclins 0 Fungal Proteins 0 fizzy protein IM fzy Amino Acid Sequence Animal Base Sequence Cell Compartmentation Cell Cycle genetics Cell Cycle Proteins genetics immunology isolation & purification physiology Cloning, Molecular Cyclins metabolism Drosophila melanogaster embryology genetics Fungal Proteins genetics Genes, Insect genetics Immunoblotting Immunohistochemistry Microtubules metabolism Mitosis genetics physiology Mitotic Spindle Apparatus physiology Molecular Sequence Data Saccharomyces cerevisiae genetics Sequence Analysis, DNA Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0058984 93183768 8443106 1993 04 08 1993 04 08 2002 12 26

0925-4773 40 1-2 1993 Jan Control of tailless expression by bicoid, dorsal and synergistically interacting terminal system regulatory elements. 47-61 Three different maternal morphogen gradients regulate expression of the gap gene tailless (tll), which is required to establish the acron and telson of the Drosophila embryo. To identify elements in the tll promoter that respond to these different maternal systems, we have generated promoter-lacZ fusions and transformed them into the germline. Expression of these constructs in both wild type and mutant embryos revealed the presence of at least two separate but synergistically interacting regions that mediate tll expression by the terminal system. This functional synergism between regulatory elements may play a role in the translation of the torso (tor) morphogen gradient into the sharp boundary of tll gene activity. In addition to regions mediating activation by the terminal system, regions mediating both activation and repression by bicoid (bcd), and repression by dorsal (dl) were identified. Binding sites of bcd protein in a 0.5 kb region, revealed by DNaseI footprinting, could be crucial for the bcd-dependent activation of tll expression in the anterior stripe. Department of Biology, University of California, Los Angeles 90024-1606. Liaw G J GJ Lengyel J A JA eng Journal Article

IRELAND Mech Dev 9101218 0 Insect Hormones 0 bicoid protein, Drosophila IM Animal Base Sequence Binding Sites DNA Mutational Analysis Drosophila melanogaster embryology genetics Gene Expression Regulation drug effects Insect Hormones metabolism pharmacology Molecular Sequence Data Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0108681 99282502 10353904 1999 07 08 1999 07 08 2000 12 18

0016-6731 152 2 1999 Jun Evidence for complex mutations at microsatellite loci in Drosophila. 617-27 Fifteen lines each of Drosophila melanogaster, D. simulans, and D. sechellia were scored for 19 microsatellite loci. One to four alleles of each locus in each species were sequenced, and microsatellite variability was compared with sequence structure. Only 7 loci had their size variation among species consistent with the occurrence of strictly stepwise mutations in the repeat array, the others showing extensive variability in the flanking region compared to that within the microsatellite itself. Polymorphisms apparently resulting from complex nonstepwise mutations involving the microsatellite were also observed, both within and between species. Maximum number of perfect repeats and variance of repeat count were found to be strongly correlated in microsatellites showing an apparently stepwise mutation pattern. These data indicate that many microsatellite mutation events are more complex than represented even by generalized stepwise mutation models. Care should therefore be taken in inferring population or phylogenetic relationships from microsatellite size data alone. The analysis also indicates, however, that evaluation of sequence structure may allow selection of microsatellites that more closely match the assumptions of stepwise models. Department of Zoology, University of Oxford, Oxford, OX1 3PS, United Kingdom. Colson I I Goldstein D B DB eng GENBANK AF067866 AF067867 AF067868 AF067869 AF067870 AF067871 AF067872 AF067873 AF067874 AF067875 AF067876 AF067877 AF067878 AF067879 AF067880 AF067881 AF067882 AF067883 AF067884 AF067885 AF067886 AF067887 AF067888 AF067889 AF067890 AF067891 AF067892 AF067893 AF067894 AF067895 Journal Article

UNITED STATES Genetics 0374636 0 Genetic Markers 9007-49-2 DNA IM Animal Base Sequence DNA chemistry genetics Drosophila genetics Genetic Markers Microsatellite Repeats genetics Molecular Sequence Data Mutation Polymorphism (Genetics) Sequence Alignment Sequence Analysis, DNA Sequence Homology, Nucleic Acid Species Specificity Support, Non-U.S. Gov't Variation (Genetics) FBrf0089555 96347573 8756662 1996 09 26 1996 09 26 2002 11 01

0270-7306 16 9 1996 Sep Sex-lethal interacts with splicing factors in vitro and in vivo. 5036-47 The Drosophila sex determination gene Sex-lethal controls its own expression and the expression of downstream target genes such as transformer by regulating RNA splicing. Genetic and molecular studies have established that Sxl requires the product of another gene, snf, to autoregulate the splicing of its own transcripts. snf has recently been shown to encode a Drosophila U1 and U2 small nuclear ribonucleoprotein particle protein. In the work reported here, we demonstrate that the Sxl and Snf proteins can interact directly in vitro and that these two proteins are part of an RNase-sensitive complex in vivo which can be immunoprecipitated with the Sxl antibody. Unlike bulk Snf protein, which sediments slowly in sucrose gradients, the Snf protein associated with Sxl is in a large, rapidly sedimenting complex. Detailed characterization of the Sxl-Snf complexes from cross-linked extracts indicates that these complexes contain additional small nuclear ribonucleoprotein particle proteins and the U1 and U2 small nuclear RNAs. Finally, consistent with the RNase sensitivity of the Sxl-Snf complexes, Sxl transcripts can also be immunoprecipitated by Sxl antibodies. On the basis of the physical interactions between Sxl and Snf, we present a model for Sxl splicing regulation. This model helps explain how the Sxl protein is able to promote the sex-specific splicing of Sxl transcripts, utilizing target sequences that are distant from the regulated splice sites. Department of Molecular Biology, Princeton University, New Jersey 08544, USA. Deshpande G G Samuels M E ME Schedl P D PD eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 Antibodies, Monoclonal 0 Macromolecular Systems 0 RNA-Binding Proteins 0 Ribonucleoprotein, U1 Small Nuclear 0 SNF protein 0 Sxl protein, Drosophila IM Animal Antibodies, Monoclonal immunology Base Sequence Drosophila melanogaster genetics Gene Expression Regulation Macromolecular Systems Models, Genetic Molecular Sequence Data RNA Splicing physiology RNA-Binding Proteins immunology physiology Ribonucleoprotein, U1 Small Nuclear physiology Sex Determination (Analysis) Support, Non-U.S. Gov't FBrf0080198 95194372 1365903 1995 04 10 1995 04 10 2000 12 18

0265-9247 14 8 1992 Aug Molecular movements in oocyte patterning and pole cell differentiation. 507-12 Central to the differentiation and patterning of the Drosophila oocyte is the asymmetric intracellular localization of numerous mRNA and protein molecules involved in developmental signalling. Recent advances have identified some of the molecules mediating oocyte differentiation, specification of the anterior pole of the embryo, and determination of the embryonic germ line. This work is considered in the context of the classical model of the germ plasm as a cytoplasmic determinant for germ cell formation. Department of Biology, McGill University, Montreal, PQ, Canada. Lasko P F PF eng Journal Article Review Review, Tutorial

ENGLAND Bioessays 8510851 IM Bic-D capu egl osk spor stau tud vas vasa Animal Cell Compartmentation Cell Differentiation Cell Polarity Cytoplasm physiology Drosophila melanogaster cytology embryology genetics Embryo, Nonmammalian metabolism ultrastructure Gene Expression Regulation, Developmental Oocytes physiology ultrastructure Oogenesis Support, Non-U.S. Gov't 66 FBrf0052844 90272714 2161539 1990 07 12 1990 07 12 2000 12 18

0027-8424 87 11 1990 Jun Potentiation of a polyadenylylation site by a downstream protein-DNA interaction. 4373-7 The gypsy retroposon of Drosophila melanogaster contains a sequence that potentiates upstream polyadenylylation sites. In contrast to other sequences that influence poly(A) site use, it appears to operate at the level of the DNA template. Nuclear extracts contained protein that bound to a repeated motif in the DNA. Flies with mutations that reduced transcripts polyadenylylated in the 5' long terminal repeat of gypsy contained less DNA-binding activity than wild type. A change in the repeat motif reduced both protein binding and poly(A) site potentiation. These findings provide evidence that DNA-binding proteins can regulate polyadenylylation sites. Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021. Dorsett D D eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA Transposable Elements 0 DNA-Binding Proteins 0 Nuclear Proteins 24937-83-5 Poly A IM Animal Base Sequence DNA Mutational Analysis DNA Transposable Elements DNA-Binding Proteins physiology Drosophila melanogaster genetics Gene Expression Molecular Sequence Data Mutation Nuclear Proteins physiology Poly A metabolism Protein Binding Repetitive Sequences, Nucleic Acid Transcription, Genetic FBrf0104429 98337843 9671597 1998 09 28 1998 09 28 2002 11 01

0950-1991 125 16 1998 Aug Key aspects of the primary sex determination mechanism are conserved across the genus Drosophila. 3259-68 In D. melanogaster, a set of 'X:A numerator genes', which includes sisterlessA (sisA), determines sex by controlling the transcription of Sex-lethal (Sxl). We characterized sisA from D. pseudoobscura and D. virilis and studied the timing of sisA and Sxl expression with single cell-cycle resolution in D. virilis, both to guide structure-function studies of sisA and to help understand sex determination evolution. We found that D. virilis sisA shares 58% amino acid identity with its melanogaster ortholog. The identities confirm sisA as an atypical bZIP transcription factor. Although virilis sisA can substitute for melanogaster sisA, the protein is not fully functional in a heterologous context. The putative sisA regulatory sequence CAGGTAG is a potential 'numerator box,' since it is shared with the other strong X:A numerator gene, sisB, and its target, SxlPe. Temporal and spatial features of sisA and SxlPe expression are strikingly conserved, including rapid onset and cessation of transcription in somatic nuclei, early cessation of sisA transcription in budding pole cells and persistent high-level sisA expression in yolk nuclei. Expression of sisA and Sxl is as tightly coupled in virilis as it is in melanogaster. Taken together, these data indicate that the same primary sex determination mechanism exists throughout the genus Drosophila. Department of Molecular and Cell Biology, Division of Genetics, University of California, Berkeley, CA 94720-3204, USA. Erickson J W JW Cline T W TW eng GENBANK AF045585 AF045586 AF045587 AF046044 AF046045 GM23468 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 0 Transcription Factors 0 scute protein, Drosophila 0 sisterless-a protein IM Amino Acid Sequence Animal Conserved Sequence genetics DNA-Binding Proteins chemistry Drosophila physiology Gene Expression Regulation, Developmental genetics Genes, Insect genetics In Situ Hybridization Molecular Sequence Data Promoter Regions (Genetics) genetics RNA-Binding Proteins chemistry Sequence Analysis, DNA Sequence Homology, Amino Acid Sex Determination (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription Factors chemistry FBrf0084674 96133695 8544820 1996 02 09 1996 02 09 2003 06 16

0026-8925 249 5 1995 Dec 15 Characterization of an EcR/USP heterodimer target site that mediates ecdysone responsiveness of the Drosophila Lsp-2 gene. 545-56 The Larval serum protein-2 gene (Lsp-2) of Drosophila melanogaster is uniquely expressed in the fat body tissue from the beginning of the third instar to the end of adult life. Accumulation of the larval Lsp-2 transcript is enhanced by 20-hydroxyecdysone. To study the molecular basis for ecdysone regulated Lsp-2 activity, deletion mutants of the Lsp-2 5'-flanking region were constructed by fusion to either the Escherichia coli chloramphenicol acetyltransferase (CAT) gene or to an hsp70-lacZ hybrid gene encoding beta-galactosidase. Constructs transfected into Drosophila S2/M3 cells were shown to confer transient ecdysone inducibility on the reporter genes. A single functional ecdysone response element (EcRE) was localized at position -75 relative to the Lsp-2 transcription initiation site. In gel mobility shift assays using fat body nuclear extracts or nuclear receptors synthesized in vitro, a 27-bp sequence harboring the EcRE bound both the Drosophila ecdysone receptor and the Drosophila retinoid-X homologue, Ultraspiracle, in a cooperative manner. Competition experiments indicate that the affinity of the Lsp-2 EcRE for the ecdysone receptor complex is comparable to that of the canonical EcRE of the hsp27 gene and is at least 4-fold greater than that of Fbp1, another fat body-specific Drosophila gene. Our results suggest that structural features of this EcRE determine its ability to induce ecdysone responsiveness at a lower ligand concentration and may form the basis for differential hormone responsiveness within the fat body. Institut Jacques Monod, Centre National de la Recherche Scientifique and Université de Paris 7, France. Antoniewski C C O'Grady M S MS Edmondson R G RG Lassieur S M SM Benes H H eng Journal Article

GERMANY Mol Gen Genet 0125036 0 CF1 protein 0 DNA-Binding Proteins 0 Insect Hormones 0 Receptors, Steroid 0 Transcription Factors 0 ecdysone receptor 0 larval serum protein, Drosophila 3604-87-3 Ecdysone 9007-49-2 DNA IM Mol Gen Genet 1996 Aug 27;252(1-2):221 Animal Base Sequence Binding Sites Cell Line DNA genetics metabolism DNA-Binding Proteins metabolism Drosophila melanogaster genetics Ecdysone metabolism Genes, Insect Insect Hormones genetics metabolism Molecular Sequence Data Promoter Regions (Genetics) Receptors, Steroid metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription Factors metabolism FBrf0090446 97082052 8923295 1997 03 11 1997 03 11 2000 12 18

0167-7063 10 4 1996 Sep Genetic analysis of the lozenge gene complex in Drosophila melanogaster: adult visual system phenotypes. 193-220 Mutations at the lozenge (lz) locus are pleiotropic, primarily affecting the sense organs for sight, smell and taste. To better understand the role that lz plays in the visual system, we investigated its complex genetics and the effect mutations have on the structure of the compound eye. Complementation analysis within the lz locus reveals two functional units necessary for a normal eye, cistrons A and B. Previous recombination studies identified four subloci spanning 0.14 m.u. Cistron A mutations map to the distal-most spectacle sub-locus, which has been identified as an insertion point for P-elements. Southern blotting and chromosomal in situ hybridization show that P-allele lzmu2 contains a single P-element; a cosmid clone derived from lzmu2 confirms that the P-element is defective. Mutants of both cistrons perturb lens structure and eye pigmentation. However, the extent of the defects differs between the most severe mutations of the two cistrons. Within the eye, failure to form the fenestrated membrane permits photoreceptor neurons to "fall" into the brain disrupting neural structure. Our analysis shows that lz exerts control over the identity of cone cells, pigment cells and photoreceptor neurons. University of Melbourne, Parkville, Victoria, Australia. Batterham P P Crew J R JR Sokac A M AM Andrews J R JR Pasquini G M GM Davies A G AG Stocker R F RF Pollock J A JA eng 5T32GM08067-100031 GM NIGMS EY09093 EY NEI Journal Article

ENGLAND J Neurogenet 8406473 IM Alleles Animal Chromosome Mapping Cloning, Molecular Drosophila melanogaster genetics Eye anatomy & histology Genes, Insect Genes, Structural Genetic Complementation Test Mutagenesis Optic Lobe anatomy & histology Phenotype Recombination, Genetic Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Vision genetics FBrf0078360 95124348 7823955 1995 02 16 1995 02 16 2000 12 18

0270-7306 15 2 1995 Feb Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. 904-17 The choice of sexual identity in somatic tissues of the fruit fly Drosophila melanogaster is determined early in embryogenesis by the X-chromosome-to-autosome (X/A) ratio. The system that signals the X/A ratio selects the sexual development pathway by determining the activity state of the binary switch Sex-lethal (Sxl). In 2X/2A animals, the X/A signalling system turns the Sxl gene on, ultimately activating an RNA-splicing autoregulatory feedback loop which serves to maintain the female state during the remainder of development. In 1X/2A animals, this autoregulatory feedback loop is not activated and the male state is subsequently maintained by the default splicing machinery. In the studies reported here, we have examined how the X/A signalling system controls the initial choice of sexual identity through its action on a special early embryonic Sxl promoter, Sxl-Pe. We show that in the early embryo, the activity of Sxl-Pe is controlled in a highly dose-sensitive fashion by the genes on the X chromosome that function as numerator elements and by genes located on the autosomes that function as denominator elements. Functional dissection of Sxl-Pe indicates that activating the promoter in females requires the cumulative action of multiple numerator genes which appear to exert their effects through reiterated cis-acting target sites in the promoter. Conversely, maintaining the promoter silent in males requires the repressive activities of denominator genes, and at least one of the denominator genes also appears to function through target sequences within the promoter. Department of Molecular Biology, Princeton University, New Jersey 08544. Estes P A PA Keyes L N LN Schedl P P eng Journal Article

UNITED STATES Mol Cell Biol 8109087 IM Scl Scl-Pe sis-a sis-b Animal Crosses, Genetic Drosophila melanogaster genetics physiology Female Gene Deletion Gene Expression Regulation Genes, Insect Genes, Lethal Male Models, Genetic Multigene Family Promoter Regions (Genetics) Sex Characteristics Signal Transduction Transformation, Genetic X Chromosome FBrf0048245 88284311 2840331 1988 08 26 1988 08 26 2000 12 18

0016-6731 119 1 1988 May P element insertions and rearrangements at the singed locus of Drosophila melanogaster. 75-83 DNA from the singed gene of Drosophila melanogaster was isolated using an inversion between a previously cloned P element at cytological location 17C and the hypermutable allele singed-weak. Five out of nine singed mutants examined have alterations in their DNA maps in this region. The singed locus is a hotspot for mutation during P-M hybrid dysgenesis, and we have analyzed 22 mutations induced by P-M hybrid dysgenesis. All 22 have a P element inserted within a 700-bp region. The precise positions of 10 P element insertions were determined and they define 4 sites within a 100-bp interval. During P-M hybrid dysgenesis, the singed-weak allele is destabilized, producing two classes of phenotypically altered derivatives at high frequency. In singed-weak, two defective P elements are present in a "head-to-head" or inverse tandem arrangement. Excision of one element results in a more extreme singed bristle phenotype while excision of the other leads to a wild-type bristle phenotype. Department of Biochemistry, University of California, Berkeley 94720. Roiha H H Rubin G M GM O'Hare K K eng GENBANK Y00614 GM33135 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 DNA, Recombinant IM Alleles Animal Chromosome Mapping Cloning, Molecular DNA Transposable Elements DNA, Recombinant Drosophila melanogaster genetics Mutation Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0137213 21341787 11448635 2001 07 12 2001 11 01

0959-437X 11 4 2001 Aug Wing disc development in the fly: the early stages. 470-5 The establishment of the wing anlage in Drosophila is dependent on the presence of two organizing centers located at the boundaries of the dorsoventral and anteroposterior compartments. How these boundaries are defined was not understood until recently. Furthermore, nothing was known about how the hinge region of the wing is defined. Recent data have now started to provide some insight in the molecular processes required for the definition of the major boundaries and subdivision of the wing anlage into the hinge and blade region. Institut für Genetik, Universität zu Köln, Weyertal 121, 50931, Köln, Germany. th.klein@uni-koeln.de Klein T T eng Journal Article Review Review, Tutorial

England Curr Opin Genet Dev 9111375 IM Animal Drosophila melanogaster growth & development Support, Non-U.S. Gov't Wing growth & development 30 FBrf0128393 20283933 10823947 2000 06 30 2000 06 30 2000 12 18

0027-8424 97 11 2000 May 23 Reduced X-linked nucleotide polymorphism in Drosophila simulans. 5960-5 Population genetic theory predicts that selectively driven changes of allele frequency for both beneficial and deleterious mutants reduce polymorphism at tightly linked sites. All else being equal, these reductions in polymorphism are expected to be greater when recombination rates are lower. Therefore, the empirical observation of a positive correlation between recombination rates and amounts of DNA polymorphism across the Drosophila melanogaster genome can be explained by two very different types of natural selection. Here, we evaluate alternative models of effects of selection on linked sites by comparison of X-linked and autosomal variation. We present polymorphism data from 40 genes distributed across chromosome arms X and 3R of Drosophila simulans, a sibling species of D. melanogaster. We find significantly less silent polymorphism in D. simulans on the X chromosome than on 3R, but no difference between arms for silent divergence between species. This pattern is incompatible with predictions from theoretical studies on the effect of negative selection on linked sites. We propose that some form of positive selection having greater effects on sex chromosomes than on autosomes is the better explanation for the D. simulans data. Section of Integrative Biology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA. djbegun@mail.utexas.edu Begun D J DJ Whitley P P eng GENBANK AF204277 AF204278 AF204279 AF204280 AF204281 AF204282 AF204283 AF204284 AF204285 AF204286 AF204287 AF204288 AF204289 AF204290 AF256057 AF256058 AF256059 AF256060 AF256061 AF256062 AF256063 AF256064 AF256065 AF256066 AF256067 AF256068 AF256069 AF256070 AF256071 AF256072 GM55298 GM NIGMS Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 IM Animal Comparative Study Drosophila genetics Genes, Insect Genetics, Population In Vitro Male Molecular Sequence Data Polymorphism (Genetics) genetics Selection (Genetics) Support, U.S. Gov't, P.H.S. X Chromosome genetics FBrf0057925 93251922 8486077 1993 06 10 1993 06 10 2002 11 01

0009-5915 102 4 1993 Mar A combined molecular and cytogenetic approach to genome evolution in Drosophila using large-fragment DNA cloning. 253-66 Methods of genome analysis, including the cloning and manipulation of large fragments of DNA, have opened new strategies for uniting molecular evolutionary genetics with chromosome evolution. We have begun the development of a physical map of the genome of Drosophila virilis based on large DNA fragments cloned in bacteriophage P1. A library of 10,080 P1 clones with average insert sizes of 65.8 kb, containing approximately 3.7 copies of the haploid genome of D. virilis, has been constructed and characterized. Approximately 75% of the clones have inserts exceeding 50 kb, and approximately 25% have inserts exceeding 80 kb. A sample of 186 randomly selected clones was mapped by in situ hybridization with the salivary gland chromosomes. A method for identifying D. virilis clones containing homologs of D. melanogaster genes has also been developed using hybridization with specific probes obtained from D. melanogaster by means of the polymerase chain reaction. This method proved successful for nine of ten genes and resulted in the recovery of 14 clones. The hybridization patterns of a sample of P1 clones containing repetitive DNA were also determined. A significant fraction of these clones hybridizes to multiple euchromatic sites but not to the chromocenter, which is a pattern of hybridization that is very rare among clones derived from D. melanogaster. The materials and methods described will make it possible to carry out a direct study of molecular evolution at the level of chromosome structure and organization as well as at the level of individual genes. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138. Lozovskaya E R ER Petrov D A DA Hartl D L DL eng HG00357 HG NHGRI HG00750 HG NHGRI Journal Article

GERMANY Chromosoma 2985138R 0 DNA, Ribosomal 9007-49-2 DNA IM Animal Base Sequence Chromosome Mapping Chromosomes ultrastructure Cloning, Molecular Comparative Study Cytogenetics DNA genetics DNA, Ribosomal genetics Drosophila genetics Drosophila melanogaster genetics Evolution Gene Library In Situ Hybridization Molecular Biology Molecular Sequence Data Polymerase Chain Reaction Repetitive Sequences, Nucleic Acid Species Specificity Support, U.S. Gov't, P.H.S. FBrf0086941 96304592 8722779 1996 10 11 1996 10 11 2000 12 18

0016-6731 143 1 1996 May Single amino acid mutations in Drosophila fascin disrupt actin bundling function in vivo. 249-58 Fascins bundle actin filaments into large, tightly packed hexagonal arrays that support diverse cellular processes including microvillar projections and filopodial extensions. In Drosophila, fascin is encoded by the singed locus. Severe singed mutants have gnarled bristles and are female sterile due to a defect in rapid cytoplasm transport during oogenesis. In this paper, we report the results of a large EMS mutagenesis screen to generate new singed alleles. A mutation that changes glycine 409 to glutamic acid results in partial inactivation of fascin in vivo; singedG409E mutants have kinked bristles and are fertile with a mild nurse cell cytoplasm transport defect. This mutation is in a small conserved domain near the C-terminus of fascin. A mutation that changes serine 289 to asparagine almost completely inactivates fascin in vivo; singedS289N mutants have gnarled bristles and are sterile due to a severe defect in nurse cell cytoplasm transport caused by the absence of nurse cell cytoplasmic actin bundles. A subsequent EMS mutagenesis screen for dominant suppressors of singedS289N sterility revealed an intragenic suppressor mutation that changes serine 251 to phenylalanine and restores much of fascin's function. These two mutations, S289N and S251F, draw attention to a central domain in fascin. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA. Cant K K Cooley L L eng GM-07205 GM NIGMS GM-43301 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Actins 0 Carrier Proteins 0 Microfilament Proteins 0 Recombinant Proteins 146808-54-0 fascin 62-50-0 Ethyl Methanesulfonate IM Actins metabolism Alleles Amino Acid Sequence Animal Carrier Proteins biosynthesis genetics metabolism Crosses, Genetic Cytoplasm metabolism Drosophila melanogaster genetics metabolism Ethyl Methanesulfonate Female Genes, Insect Male Microfilament Proteins biosynthesis metabolism Molecular Sequence Data Mutagenesis Point Mutation Recombinant Proteins biosynthesis metabolism Sea Urchins Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0054607 92102951 1684714 1992 02 07 1992 02 07 2000 12 18

0925-4773 35 2 1991 Sep Molecular characterization of the trithorax gene, a positive regulator of homeotic gene expression in Drosophila. 113-27 The Drosophila gene trithorax (trx) is required for the normal expression of a number of the homeotic genes in the bithorax complex (BX-C) and the Antennapedia complex (ANT-C). Flies homozygous for trx mutations exhibit segmental identity transformations similar to those caused by loss-of-function mutations in the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B). We present a molecular characterization of the trx locus and show that it is necessary for normal levels of Antennapedia (Antp), Ubx, and abd-A protein accumulation. Interestingly, the loss of trx function differentially affects the expression these proteins; Ubx protein levels are greatly reduced, abd-A protein levels are reduced to a lesser extent, and Antp protein levels are only slightly reduced. P-element mediated transformation using 34 kb of genomic DNA containing the 25 kb trx transcription unit identifies all sequences necessary for normal trx function and limits the 5' and 3' flanking sequences that could be used in a regulatory capacity to relatively small regions. The primary transcription unit is differentially spliced to produce two large transcripts of 12 and 15 kb that have different developmental profiles. Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106. Breen T R TR Harte P J PJ eng GM-39255 GM NIGMS Journal Article

IRELAND Mech Dev 9101218 0 Genetic Markers 0 RNA, Messenger IM Antp Df(3R)red<up>P52</up> Scr T(Y;3)red<up>P4</up> Ubx abd-A l(3)JY16 l(3)M41 l(3)Z23 red<up>C1</up> st su(Hw) su(Hw)<up>V</up> trx trx<up>1</up> trx<up>3</up> trx<up>B11</up> trx<up>B14</up> Animal Chromosome Mapping Drosophila melanogaster embryology genetics Gene Expression Regulation Genes, Homeobox Genes, Regulator Genetic Markers Nervous System embryology RNA, Messenger biosynthesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0051363 90322423 1973634 1990 08 30 1990 08 30 2000 12 18

0092-8674 62 2 1990 Jul 27 Induction across germ layers in Drosophila mediated by a genetic cascade. 261-8 We report an induction process occurring between two germ layers in the Drosophila embryo that involves a cascade of five interacting genes. Two of these, Ultrabithorax and abdominal-A, encode nuclear homeobox proteins; each of them is expressed in one of two adjacent parasegments in the visceral mesoderm and directs expression in its parasegment of a separate target gene, decapentaplegic in parasegment 7 and wingless in parasegment 8. The activity of both target genes is required for normal expression of another homeotic gene, labial, in cells of the adhering midgut epithelium. Their products are putative extracellular proteins, which presumably act as signals between the two germ layers. Positional instruction of this kind may be needed since the endoderm, unlike the mesoderm, appears unsegmented at first as it originates from two primordia near the embryonic poles, outside the realm of segmentation genes. Zoological Institute, University of Zurich, Switzerland. Immerglück K K Lawrence P A PA Bienz M M eng Journal Article

UNITED STATES Cell 0413066 0 RNA, Messenger IM Animal Cell Differentiation Drosophila melanogaster embryology genetics Embryonic Induction Endoderm physiology Gene Expression Regulation Genes, Homeobox Intestines embryology Mesoderm Nucleic Acid Hybridization RNA, Messenger genetics Support, Non-U.S. Gov't FBrf0058587 93292926 8514133 1993 07 20 1993 07 20 2000 12 18

0016-6731 134 1 1993 May Suppression of a lethal trisomic phenotype in Drosophila melanogaster by increased dosage of an unlinked locus. 243-9 One of the most extreme examples of gene dosage sensitivity is the Triplo-lethal locus (Tpl) on the third chromosome of Drosophila melanogaster, which is lethal when present in either one or three copies. Increased dosage of an unlinked locus, Isis, suppresses the triplo-lethal phenotype of Tpl, but not the haplo-lethal phenotype. We have mapped Isis to the X chromosome region 7E3-8A5, and shown that the suppression is a gene dosage effect. Altered dosage of Isis in the presence of two copies of Tpl has no obvious effects. By examining the interactions between Isis dosage and Tpl we suggest that Isis does not directly repress Tpl expression, but acts downstream on the triplo-lethal phenotype of Tpl. Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541. Dorer D R DR Cadden M A MA Gordesky-Gold B B Harries G G Christensen A C AC eng R29-GM38483 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 IM Tpl Animal Chromosome Mapping Drosophila melanogaster genetics Female Genes, Lethal Linkage (Genetics) Male Multigene Family Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Suppression, Genetic Translocation (Genetics) Trisomy X Chromosome Y Chromosome FBrf0156100 22436423 12547518 2003 01 27 2003 04 16

0168-9525 19 2 2003 Feb Patterning the fly eye: the role of apoptosis. 91-6 Early development in many tissues is characterized by a rapid expansion in cell number. Excess cells are removed through activation of their intrinsic apoptotic machinery. This over-expansion followed by selective removal is important for the sculpting of these tissues, and how specific cells are selected to die is one of the central questions in development. The Drosophila eye is a unique example of such patterning through cell death. Because of its remarkable reiterative design, the fly eye lends itself to studies of mutants with increased or decreased apoptosis. We know that the process of elimination of lattice cells is highly regulated. And we have learned that each ommatidial unit is involved in the life-death decision of lattice cells through cell-cell signaling. But, we have yet to understand how this signaling is regulated spatially to result in such precision. In this article, we describe and speculate on the role of selective cell death during maturation of the fly eye. Developmental and Cell Biology, University of California, Irvine, 5205 McGaugh Hall, Irvine, CA 92697-2300, USA. Brachmann Carrie Baker CB Cagan Ross L RL eng Journal Article Review Review, Tutorial

England Trends Genet 8507085 EC 3.4.22.- Caspases IM Animal Apoptosis physiology Body Patterning Caspases metabolism Cell Death Drosophila melanogaster embryology Embryo, Nonmammalian cytology Eye anatomy & histology embryology ultrastructure Models, Biological Mutation Retina cytology Signal Transduction Support, Non-U.S. Gov't 44 FBrf0055876 92249213 1349523 1992 06 05 1992 06 05 2000 12 18

0950-1991 114 1 1992 Jan Organogenesis in Drosophila melanogaster: embryonic salivary gland determination is controlled by homeotic and dorsoventral patterning genes. 49-57 We have investigated Drosophila salivary gland determination by examining the effects of mutations in pattern forming genes on the salivary gland primordium. We find that the anterior-posterior extent of the primordium, a placode of columnar epithelial cells derived from parasegment 2, is established by the positive action of the homeotic gene Sex combs reduced (Scr). Embryos mutant for Scr lack a detectable placode, while ectopic Scr expression leads to the formation of ectopic salivary glands. In contrast, the dorsal-ventral extent of the placode is regulated negatively. Functions dependent on the decapentaplegic product place a dorsal limit on the placode, while dorsal-dependent genes act to limit the placode ventrally. We propose a model in which these pattern forming genes act early to determine the salivary gland anlage by regulating the expression of salivary gland determining genes, which in turn control genes that are involved in salivary gland morphogenesis. Department of Molecular and Cell Biology, University of California, Berkeley 94720. Panzer S S Weigel D D Beckendorf S K SK eng GM35668 GM NIGMS Journal Article

ENGLAND Development 8701744 IM Animal Drosophila melanogaster embryology genetics Genes, Homeobox physiology Genes, Structural physiology Immunohistochemistry Models, Genetic Morphogenesis genetics Mutation genetics Salivary Glands embryology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0080135 95148612 7846045 1995 03 03 1995 03 03 2003 06 16

0027-8424 92 3 1995 Jan 31 Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction. 739-43 The Drosophila homeotic selector (HOM) genes encode a family of DNA binding transcription factors that specify developmental fates of different body segments by differentially regulating the activity of downstream target genes. A central question is how the HOM proteins achieve their developmental specificity despite the very similar DNA binding specificities of isolated HOM proteins in vitro. Specificity could be achieved by differential interactions with protein cofactors. The extradenticle gene might encode such a cofactor since it interacts genetically in parallel with Ultrabithorax, abdominal-A, and perhaps other HOM genes. By using a yeast two-hybrid system, we demonstrate selective interaction of the extradenticle homeodomain protein with certain Ultrabithorax and abdominal-A proteins but not with an Antennapedia protein or a more distant homeodomain protein. Strong interaction with Ultrabithorax proteins requires only the Ultrabithorax homeodomain and a 15-residue N-terminal extension that includes Tyr-Pro-Trp-Met (YPWM), a tetrapeptide motif found near the homeodomain in most HOM proteins and their mammalian Hox counterparts. The size and sequence of the region between the YPWM element and the homeodomain differ among Ultrabithorax isoforms, and this variable region appears to affect the interaction detected in the assay. Department of Biochemistry, Stanford University, CA 94305. Johnson F B FB Parker E E Krasnow M A MA eng Journal Article

UNITED STATES Proc Natl Acad Sci U S A 7505876 0 DNA-Binding Proteins 0 Homeodomain Proteins 0 Proteins 0 Recombinant Fusion Proteins 0 Transcription Factors 0 exd protein, Drosophila 132084-67-4 abd-A protein, Drosophila 132084-67-4 abdominal A protein, Drosophila EC 3.2.1.23 beta-Galactosidase IM Ubx abd-A exd Amino Acid Sequence Animal Binding Sites DNA-Binding Proteins genetics metabolism Drosophila melanogaster metabolism Genes, Homeobox genetics Homeodomain Proteins genetics metabolism Molecular Sequence Data Proteins genetics metabolism Recombinant Fusion Proteins biosynthesis metabolism Saccharomyces cerevisiae genetics Sequence Deletion physiology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors genetics metabolism beta-Galactosidase biosynthesis FBrf0108625 99427624 10507837 1999 09 24 1999 09 24 2002 12 27

0925-4773 83 1-2 1999 May Dishevelled: at the crossroads of divergent intracellular signaling pathways. 27-37 During the development of multicellular organisms the formation of complex patterns relies on specific cell-cell signaling events. For tissues to become spatially organized and cells to become committed to specialized fates it is absolutely crucial for proper development that the underlying signaling systems receive and route information correctly. Recently, a wealth of genetic and biochemical experimental data has been collected about prevalent evolutionary conserved signaling families, such as the Wnts, Dpp/BMPs, and Hedgehogs, in flies, worms, and vertebrates. Paradoxically, members of a particular signaling family often have receptors with similar biochemical binding properties, though they activate different intracellular pathways in vivo and can be phenotypically distinguished. How are their specific biological responses then generated? With respect to signaling specificity in Wnt pathways, Dishevelled is an intriguing protein; in Drosophila melanogaster it is required in two distinct signaling pathways, that share Frizzled receptors of similar structure, but have distinct intracellular signaling routes. Recent results suggest that Dishevelled is a multifunctional protein at the crossroads of divergent Wnt/Fz pathways. Dishevelled appears to be a key factor in Wnt signaling to read' signals coming from the plasma membrane and route them into the correct intracellular pathways. Developmental Biology, Programme, European Molecular Biology Laboratory, Meyerhofstrasse 169117, Heidelberg, Germany. Boutros M M Mlodzik M M eng Journal Article Review Review, Tutorial

IRELAND Mech Dev 9101218 0 Dsh protein 0 Membrane Proteins 0 Phosphoproteins 0 Proto-Oncogene Proteins 0 frizzled protein, Drosophila 0 proto-oncogene protein int-1 117758-26-6 wingless protein, Drosophila IM Amino Acid Sequence Animal Drosophila embryology genetics Membrane Proteins metabolism Mice Models, Genetic Molecular Sequence Data Phosphoproteins genetics physiology Proto-Oncogene Proteins metabolism Sequence Homology, Amino Acid Signal Transduction Xenopus embryology genetics 67 FBrf0131248 20547711 11094082 2000 12 13 2001 01 11 2001 11 02

0270-7306 20 24 2000 Dec Functional interaction between the coactivator Drosophila CREB-binding protein and ASH1, a member of the trithorax group of chromatin modifiers. 9317-30 CREB-binding protein (CBP) is a coactivator for multiple transcription factors that transduce a variety of signaling pathways. Current models propose that CBP enhances gene expression by bridging the signal-responsive transcription factors with components of the basal transcriptional machinery and by augmenting the access of transcription factors to DNA through the acetylation of histones. To define the pathways and proteins that require CBP function in a living organism, we have begun a genetic analysis of CBP in flies. We have overproduced Drosophila melanogaster CBP (dCBP) in a variety of cell types and obtained distinct adult phenotypes. We used an uninflated-wing phenotype, caused by the overexpression of dCBP in specific central nervous system cells, to screen for suppressors of dCBP overactivity. Two genes with mutant versions that act as dominant suppressors of the wing phenotype were identified: the PKA-C1/DCO gene, encoding the catalytic subunit of cyclic AMP protein kinase, and ash1, a member of the trithorax group (trxG) of chromatin modifiers. Using immunocolocalization, we showed that the ASH1 protein is specifically expressed in the majority of the dCBP-overexpressing cells, suggesting that these proteins have the potential to interact biochemically. This model was confirmed by the findings that the proteins interact strongly in vitro and colocalize at specific sites on polytene chromosomes. The trxG proteins are thought to maintain gene expression during development by creating domains of open chromatin structure. Our results thus implicate a second class of chromatin-associated proteins in mediating dCBP function and imply that dCBP might be involved in the regulation of higher-order chromatin structure. Vollum Institute and Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97201, USA. Bantignies F F Goodman R H RH Smolik S M SM eng DK4Y239 DK NIDDK Journal Article

UNITED STATES Mol Cell Biol 8109087 0 ASH1 protein 0 CREB-binding protein 0 Chromatin 0 Nuclear Proteins 0 Recombinant Fusion Proteins 0 Trans-Activators 0 Transcription Factors EC 2.3.1. Acetyltransferases IM Acetyltransferases genetics metabolism Animal Animals, Genetically Modified genetics metabolism Chromatin genetics metabolism Chromosomes genetics immunology metabolism Drosophila melanogaster embryology genetics metabolism Embryo, Nonmammalian growth & development metabolism Female Gene Deletion Gene Expression Regulation Genes, Insect genetics Genes, Reporter Male Microscopy, Confocal Microscopy, Fluorescence Neurons metabolism Nuclear Proteins genetics metabolism Recombinant Fusion Proteins genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators genetics metabolism Transcription Factors genetics metabolism Wing anatomy & histology growth & development metabolism Zinc Fingers genetics FBrf0049525 89288760 2500289 1989 07 31 1989 07 31 2001 11 02

0192-253X 10 3 1989 Molecular genetics of Delta, a locus required for ectodermal differentiation in Drosophila. 261-72 Delta (Dl) is one of the six known zygotic neurogenic genes, each of which is essential for proper segregation of the embryonic ectoderm into neural and epidermal lineages. Molecular analysis of Dl reveals that it is a transcriptionally complex locus that yields multiple maternal and zygotic transcripts. DNA sequence analysis suggests that the predominant product of the locus is a putative transmembrane protein exhibiting homology to blood coagulation factors and epidermal growth factor of vertebrates. The structure of this product is consistent with the hypothesis that Dl participates in cell-cell interactions that are central to establishment of the epidermal lineage within the developing ectoderm. Genetic analyses demonstrate that Dl mutations can modify the imaginal phenotypes that result from heterozygosity for Notch (N) mutations as well as the interaction between particular alleles of Notch (N) and Enhancer of split [E(spl)], two other members of the neurogenic gene set. Vital interactions also occur between Dl and N. Given the structures of products encoded by N, Dl, and E(spl), we suggest that the synergistic phenotypic interactions observed among mutations in these three loci result from physical, as opposed to regulatory, interactions. Department of Biology, Indiana University, Bloomington 47405. Alton A K AK Fechtel K K Kopczynski C C CC Shepard S B SB Kooh P J PJ Muskavitch M A MA eng Journal Article

UNITED STATES Dev Genet 7909963 9007-49-2 DNA IM Alleles Animal DNA genetics Drosophila melanogaster genetics growth & development Ectoderm anatomy & histology Eye Abnormalities Female Mutation Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic Translation, Genetic FBrf0136863 21325907 11432817 2001 07 02 2001 08 09

0261-4189 20 13 2001 Jul 2 Nuclear interpretation of Dpp signaling in Drosophila. 3298-305 Signaling by Decapentaplegic (Dpp), a member of the TGFbeta superfamily of signaling molecules similar to vertebrate BMP2 and BMP4, has been implicated in many developmental processes in Drosophila melanogaster. Notably, Dpp acts as a long-range morphogen during imaginal disc growth and patterning. Genetic approaches led to the identification of a number of gene products that constitute the core signaling pathway. In addition to the ligand-activated heteromeric receptor complex and the signal-transducing intracellular Smad proteins, Dpp signaling requires two nuclear proteins, Schnurri (Shn) and Brinker (Brk), to prime cells for Dpp responsiveness. A complex interplay between the nuclear factors involved in Dpp signaling appears to control the transcriptional readout of the Dpp morphogen gradient. It remains to be seen whether similar molecular mechanisms operate in the nucleus in vertebrate systems. Abteilung Zellbiologie, Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4026 Basel, Switzerland. Markus.Affolter@unibas.ch Affolter M M Marty T T Vigano M A MA Jaźwińska A A eng Journal Article Review Review, Tutorial

England EMBO J 8208664 0 Insect Proteins 0 Transforming Growth Factor beta 0 dpp protein, Drosophila IM Animal Body Patterning Cell Nucleus physiology Drosophila melanogaster embryology genetics physiology Embryo, Nonmammalian physiology Insect Proteins physiology Models, Biological Morphogenesis Signal Transduction Support, Non-U.S. Gov't Transforming Growth Factor beta physiology 52 FBrf0055851 93130767 1483386 1993 02 12 1993 02 12 2000 12 18

0950-1991 116 1 1992 Sep The neurogenic locus brainiac cooperates with the Drosophila EGF receptor to establish the ovarian follicle and to determine its dorsal-ventral polarity. 177-92 We have characterized the function of a new neurogenic locus, brainiac (brn), during oogenesis. Homozygous brn females lay eggs with fused dorsal appendages, a phenotype associated with torpedo (top) alleles of the Drosophila EGF receptor (DER) locus. By constructing double mutant females for both brn and top, we have found that brn is required for determining the dorsal-ventral polarity of the ovarian follicle. However, embryos from mature brn eggs develop a neurogenic phenotype which can be zygotically rescued if a wild-type sperm fertilizes the egg. This is the first instance of a Drosophila gene required for determination of dorsal-ventral follicle cell fates that is not required for determination of embryonic dorsal-ventral cell fates. The temperature-sensitive period for brn dorsal-ventral patterning begins at the inception of vitellogenesis. The interaction between brn and DER is also required for at least two earlier follicle cell activities which are necessary to establish the ovarian follicle. Prefollicular cells fail to migrate between each oocyte/nurse cell complex, resulting in follicles with multiple sets of oocytes and nurse cells. brn and DER function is also required for establishing and/or maintaining a continuous follicular epithelium around each oocyte/nurse cell complex. These brn functions as well as the brn requirement for determination of dorsal-ventral polarity appear to be genetically separable functions of the brn locus. Genetic mosaic experiments show that brn is required in the germline during these processes whereas the DER is required in the follicle cells. We propose that brn may be part of a germline signaling pathway differentially regulating successive DER-dependent follicle cell activities of migration, division and/or adhesion and determination during oogenesis. These experiments indicate that brn is required in both tyrosine kinase and neurogenic intercellular signaling pathways. Moreover, the functions of brn in oogenesis are distinct from those of Notch and Delta, two other neurogenic loci that are known to be required for follicular development. University of Chicago, Department of Molecular Genetics and Cell Biology, Cummings Life Science Center, IL 60637. Goode S S Wright D D Mahowald A P AP eng T32 GM07197 GM NIGMS T32 HD7104 HD NICHD Journal Article

ENGLAND Development 8701744 EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Animal Drosophila melanogaster genetics Female Genes, Structural, Insect physiology Morphogenesis genetics Mutation genetics Oogenesis genetics Phenotype Receptor, Epidermal Growth Factor physiology Signal Transduction genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0105774 99077281 9862465 1999 01 14 1999 01 14 2003 06 16

0026-8925 260 2-3 1998 Nov The sugarless mutation affects the expression of the white eye color gene in Drosophila melanogaster. 131-43 Investigation of a modifier locus displaying a darker eye phenotype in white-apricot flies led to the isolation of the gene encoding UDP-glucose dehydrogenase (UDPGDH). The P-element insertion l(3)05007 occurs upstream of the transcription start site of the sugarless (sgl) gene and greatly reduces its transcription at various developmental stages. A single abundant sgl transcript shows a ubiquitous distribution and encodes a 53-kDa protein which is 64% identical in sequence to bovine UDP-glucose dehydrogenase. Overexpression of sgl in E. coli resulted in synthesis of a protein with high levels of UDPGDH activity. Expression of three genes that participate in pigment deposition, white, scarlet and brown, was significantly affected in populations segregating for sgl, suggesting that it is the decrease in UDPGDH level that produces the modifying effect observed. In addition, genetic effects on white-apricot were observed in sgl-wingless and sgl-hedgehog double mutants. Recent data have indicated an effect of UDPGDH on cell surface glycosaminoglycans (GAGs) which modulate the activity of growth factors, and in particular wingless signaling. Our results suggest that the levels of GAGs are rate limiting for cell-cell signaling pathways which mediate changes in gene expression. Division of Biological Sciences, University of Missouri-Columbia 65211, USA. Benevolenskaya E V EV Frolov M V MV Birchler J A JA eng GENBANK AF001310 AF001311 AF001312 Journal Article

GERMANY Mol Gen Genet 0125036 0 ATP-Binding Cassette Transporters 0 DNA Transposable Elements 0 Eye Proteins 0 Insect Proteins 0 Recombinant Proteins 0 bw protein, Drosophila 0 scarlet protein, Drosophila 0 white protein, Drosophila EC 1.1.1.22 Uridine Diphosphate Glucose Dehydrogenase IM ATP-Binding Cassette Transporters genetics metabolism Alleles Amino Acid Sequence Animal Cattle Cloning, Molecular DNA Transposable Elements Drosophila melanogaster genetics growth & development Escherichia coli genetics Eye Proteins genetics metabolism Female Gene Expression Regulation, Developmental Genes, Suppressor Insect Proteins genetics metabolism Male Molecular Sequence Data Mutation Recombinant Proteins genetics metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Uridine Diphosphate Glucose Dehydrogenase genetics metabolism FBrf0110270 99298190 10369678 1999 08 19 1999 08 19 2003 06 16

0261-4189 18 12 1999 Jun 15 A mosaic analysis in Drosophila fat body cells of the control of antimicrobial peptide genes by the Rel proteins Dorsal and DIF. 3380-91 Expression of the gene encoding the antifungal peptide Drosomycin in Drosophila adults is controlled by the Toll signaling pathway. The Rel proteins Dorsal and DIF (Dorsal-related immunity factor) are possible candidates for the transactivating protein in the Toll pathway that directly regulates the drosomycin gene. We have examined the requirement of Dorsal and DIF for drosomycin expression in larval fat body cells, the predominant immune-responsive tissue, using the yeast site-specific flp/FRT recombination system to generate cell clones homozygous for a deficiency uncovering both the dorsal and the dif genes. Here we show that in the absence of both genes, the immune-inducibility of drosomycin is lost but can be rescued by overexpression of either dorsal or dif under the control of a heat-shock promoter. This result suggests a functional redundancy between both Rel proteins in the control of drosomycin gene expression in the larvae of Drosophila. Interestingly, the gene encoding the antibacterial peptide Diptericin remains fully inducible in the absence of the dorsal and dif genes. Finally, we have used fat body cell clones homozygous for various mutations to show that a linear activation cascade Spaetzle--> Toll-->Cactus-->Dorsal/DIF leads to the induction of the drosomycin gene in larval fat body cells. Institut de Biologie Moléculaire et Cellulaire, UPR 9022 du Centre National de la Recherche Scientifique, 15, Rue René Descartes, F-67084 Strasbourg Cedex, France. Manfruelli P P Reichhart J M JM Steward R R Hoffmann J A JA Lemaitre B B eng Journal Article

ENGLAND EMBO J 8208664 0 Anti-Infective Agents 0 DNA-Binding Proteins 0 Dif protein 0 Insect Proteins 0 Membrane Glycoproteins 0 Nuclear Proteins 0 Phosphoproteins 0 diptericin A 0 dorsal protein, Drosophila 0 spatzle protein, Drosophila 118929-01-4 Toll protein, Drosophila 149059-01-8 cactus protein, Drosophila 159522-55-1 drosomycin IM Animal Anti-Infective Agents Clone Cells metabolism Comparative Study DNA-Binding Proteins genetics physiology Drosophila melanogaster cytology genetics immunology Fat Body metabolism Female Gene Expression Regulation Genes, Insect Genes, Reporter Insect Proteins genetics physiology Larva cytology genetics Male Membrane Glycoproteins genetics physiology Mosaicism Mutation Nuclear Proteins genetics physiology Phosphoproteins genetics physiology Signal Transduction genetics physiology Support, Non-U.S. Gov't FBrf0100677 98119834 9450931 1998 02 24 1998 02 24 2002 04 19

0890-9369 12 3 1998 Feb 1 Cdk7 is essential for mitosis and for in vivo Cdk-activating kinase activity. 370-81 Cdk7 has been shown previously to be able to phosphorylate and activate many different Cdks in vitro. However, conclusive evidence that Cdk7 acts as a Cdk-activating kinase (CAK) in vivo has remained elusive. Adding to the controversy is the fact that in the budding yeast Saccharomyces cerevisiae, CAK activity is provided by the CAK1/Civ1 protein, which is unrelated to Cdk7. Furthermore Kin28, the budding yeast Cdk7 homolog, functions not as a CAK but as the catalytic subunit of TFIIH. Vertebrate Cdk7 is also known to be part of TFIIH. Therefore, in the absence of better genetic evidence, it was proposed that the CAK activity of Cdk7 may be an in vitro artifact. In an attempt to resolve this issue, we cloned the Drosophila cdk7 homolog and created null and temperature-sensitive mutations. Here we demonstrate that cdk7 is necessary for CAK activity in vivo in a multicellular organism. We show that cdk7 activity is required for the activation of both Cdc2/Cyclin A and Cdc2/Cyclin B complexes, and for cell division. These results suggest that there may be a fundamental difference in the way metazoans and budding yeast effect a key modification of Cdks. Department of Biology, McGill University, Montreal, PQ, Canada H3A 1B1. Larochelle S S Pandur J J Fisher R P RP Salz H K HK Suter B B eng GENBANK U56661 Journal Article

UNITED STATES Genes Dev 8711660 0 Cyclins 9007-49-2 DNA EC 2.7.1.37 Protein p34cdc2 EC 2.7.1.37 Protein-Serine-Threonine Kinases EC 2.7.1.37 p40(MO15) protein IM Alleles Amino Acid Sequence Animal Cell Division physiology Chromosome Mapping Cyclins metabolism DNA isolation & purification Drosophila melanogaster genetics physiology Embryo, Nonmammalian metabolism Genes, Structural, Insect genetics Mitosis physiology Molecular Sequence Data Mutation genetics physiology Protein p34cdc2 genetics physiology Protein-Serine-Threonine Kinases genetics metabolism physiology Sequence Homology, Amino Acid Support, Non-U.S. Gov't Temperature FBrf0161020 22719031 12835379 2003 07 01 2003 09 30

0950-1991 130 16 2003 Aug Segment polarity and DV patterning gene expression reveals segmental organization of the Drosophila brain. 3607-20 The insect brain is traditionally subdivided into the trito-, deuto- and protocerebrum. However, both the neuromeric status and the course of the borders between these regions are unclear. The Drosophila embryonic brain develops from the procephalic neurogenic region of the ectoderm, which gives rise to a bilaterally symmetrical array of about 100 neuronal precursor cells, called neuroblasts. Based on a detailed description of the spatiotemporal development of the entire population of embryonic brain neuroblasts, we carried out a comprehensive analysis of the expression of segment polarity genes (engrailed, wingless, hedgehog, gooseberry distal, mirror) and DV patterning genes (muscle segment homeobox, intermediate neuroblast defective, ventral nervous system defective) in the procephalic neuroectoderm and the neuroblast layer (until stage 11, when all neuroblasts are formed). The data provide new insight into the segmental organization of the procephalic neuroectodem and evolving brain. The expression patterns allow the drawing of clear demarcations between trito-, deuto- and protocerebrum at the level of identified neuroblasts. Furthermore, we provide evidence indicating that the protocerebrum (most anterior part of the brain) is composed of two neuromeres that belong to the ocular and labral segment, respectively. These protocerebral neuromeres are much more derived compared with the trito- and deutocerebrum. The labral neuromere is confined to the posterior segmental compartment. Finally, similarities in the expression of DV patterning genes between the Drosophila and vertebrate brains are discussed. Institut für Genetik, Universität Mainz, D-55099 Mainz, Germany. Urbach Rolf R Technau Gerhard M GM eng Journal Article

England Development 8701744 0 Drosophila Proteins IM Animal Body Patterning Brain embryology Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics Ectoderm cytology physiology Gene Expression Regulation, Developmental Genes, Homeobox Genes, Reporter In Situ Hybridization Models, Anatomic Morphogenesis Support, Non-U.S. Gov't FBrf0054184 92009143 1916243 1991 11 08 1991 11 08 2000 12 18

0016-6731 128 4 1991 Aug Genetic analysis of chromosome region 63 of Drosophila melanogaster. 763-75 The salivary chromosome region including cytological division 63 of Drosophila melanogaster was genetically analyzed in order to (1) characterize this previously unstudied region and (2) attempt to isolate mutations in the hsp82 gene. Seven deletions which span this region were isolated, including four which remove the hsp82 gene. A Minute mutation was mapped to this region and this Minute was used to isolate duplications in the 63 region. These duplications map the Minute to 63B8-C1. F2 screens were initiated using deletions which remove the hsp82 gene. Over 15,000 chromosomes were screened, yielding 40 lethal mutations which comprise 14 complementation groups. Several of these mutations map outside the 63 region and appear to give second site interaction with the Minute locus. Four loci, including the Minute gene, are candidates for hsp82 mutations by cytogenetic mapping. These loci were tested for complementation with a P element carrying the hsp82 gene. However, none of the mutations was rescued. Department of Biology, Indiana University, Bloomington 47405. Wohlwill A D AD Bonner J J JJ eng GM26693 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Genetic Vectors 0 Heat-Shock Proteins IM Animal Chromosome Mapping Chromosomes Crosses, Genetic DNA Mutational Analysis Drosophila melanogaster genetics Female Genetic Vectors Heat-Shock Proteins genetics Male Support, U.S. Gov't, P.H.S. Transformation, Genetic FBrf0111512 99409636 10481910 1999 09 23 1999 09 23 2003 02 03

0092-8674 98 4 1999 Aug 20 The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. 453-63 Drosophila Reaper (RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Based on these results, we propose that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP-caspase interactions and that DIAP1 is required to block apoptosis-inducing caspase activity. Supporting this hypothesis, we show that elimination of DIAP1 function results in global early embryonic cell death and a large increase in DIAP1-inhibitable caspase activity and that DIAP1 is still required for cell survival when expression of rpr, hid, and grim is eliminated. Division of Biology MC 156-29, California Institute of Technology, Pasadena 91125, USA. Wang S L SL Hawkins C J CJ Yoo S J SJ Müller H A HA Hay B A BA eng GM057422-01 GM NIGMS Journal Article

UNITED STATES Cell 0413066 0 Fluorescent Dyes 0 Insect Proteins 0 Neuropeptides 0 Peptides 0 Recombinant Fusion Proteins 0 grim protein, Drosophila 0 head involution defective protein 0 inhibitor of apoptosis 1, Drosophila 0 reaper peptide, Drosophila 65-61-2 Acridine Orange EC 3.4.22.- Caspases IM Acridine Orange Animal Apoptosis genetics physiology Caspases antagonists & inhibitors Drosophila melanogaster embryology genetics physiology Epistasis, Genetic Fluorescent Dyes Genes, Lethal In Situ Nick-End Labeling Insect Proteins genetics physiology Morphogenesis genetics Neuropeptides genetics physiology Peptides genetics physiology Recombinant Fusion Proteins physiology Saccharomyces cerevisiae cytology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0125452 20155477 10693810 2000 03 20 2000 03 20 2003 06 16

0028-0836 403 6771 2000 Feb 17 naked cuticle encodes an inducible antagonist of Wnt signalling. 789-95 During animal development, cells have to respond appropriately to localized secreted signals. Proper responses to Hedgehog, transforming growth factor-beta, epidermal growth factor and fibroblast growth factor/Ras signals require cognate inducible antagonists such as Patched, Dad, Argos and Sprouty. Wnt signals are crucial in development and neoplasia. Here we show that naked cuticle (nkd), a Drosophila segment-polarity gene, encodes an inducible antagonist for the Wnt signal Wingless (Wg). In fly embryos and imaginal discs nkd transcription is induced by Wg. In embryos, decreased nkd function has an effect similar to excess Wg; at later stages such a decrease appears to have no effect. Conversely, overproduction of Nkd in Drosophila and misexpression of Nkd in the vertebrate Xenopus laevis result in phenotypes resembling those of loss of Wg/Wnt function. nkd encodes a protein with a single EF hand (a calcium-binding motif) that is most similar to the recoverin family of myristoyl switch proteins. Nkd may therefore link ion fluxes to the regulation of the potency, duration or distribution of Wnt signals. Signal-inducible feedback antagonists such as nkd may limit the effects of Wnt proteins in development and disease. Department of Developmental Biology, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, California 94305, USA. Zeng W W Wharton K A KA Jr Mack J A JA Wang K K Gadbaw M M Suyama K K Klein P S PS Scott M P MP eng GENBANK AF213376 Journal Article

ENGLAND Nature 0410462 0 Insect Proteins 0 Proto-Oncogene Proteins 0 dpp protein, Drosophila 0 naked cuticle protein, Drosophila 117758-26-6 wingless protein, Drosophila IM Amino Acid Sequence Animal Cloning, Molecular Drosophila melanogaster Gene Expression Regulation, Developmental Insect Proteins genetics metabolism physiology Molecular Sequence Data Proto-Oncogene Proteins antagonists & inhibitors Sequence Homology, Amino Acid Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Xenopus FBrf0141281 21556880 11700289 2001 11 08 2002 01 15

0066-4197 35 2001 Conservation and divergence in molecular mechanisms of axis formation. 407-37 Genetic screens in Drosophila melanogaster have helped elucidate the process of axis formation during early embryogenesis. Axis formation in the D. melanogaster embryo involves the use of two fundamentally different mechanisms for generating morphogenetic activity: patterning the anteroposterior axis by diffusion of a transcription factor within the syncytial embryo and specification of the dorsoventral axis through a signal transduction cascade. Identification of Drosophila genes involved in axis formation provides a launch-pad for comparative studies that examine the evolution of axis specification in different insects. Additionally, there is similarity between axial patterning mechanisms elucidated genetically in Drosophila and those demonstrated for chordates such as Xenopus. In this review we examine the postfertilization mechanisms underlying axis specification in Drosophila. Comparative data are then used to ask whether aspects of axis formation might be derived or ancestral. Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA. Lall S S Patel N H NH eng Journal Article Review Review, Academic

United States Annu Rev Genet 0117605 IM Animal Body Patterning genetics Cell Polarity Comparative Study Drosophila melanogaster cytology embryology genetics Female Gene Expression Regulation, Developmental Morphogenesis Signal Transduction Support, Non-U.S. Gov't 199 FBrf0147188 21902072 11904431 2002 03 20 2002 04 24 2003 03 28

0027-8424 99 6 2002 Mar 19 A screen for dominant mutations applied to components in the Drosophila EGF-R pathway. 3752-7 The Drosophila epidermal growth factor receptor (EGF-R) controls many critical cell fate choices throughout development. Several proteins collaborate to promote localized EGF-R activation, such as Star and Rhomboid (Rho), which act sequentially to ensure the maturation and processing of inactive membrane-bound EGF ligands. To gain insights into the mechanisms underlying Rho and Star function, we developed a mutagenesis scheme to isolate novel overexpression activity (NOVA) alleles. In the case of rho, we isolated a dominant neomorphic allele, which interferes with Notch signaling, as well as a dominant-negative allele, which produces RNA interference-like flip-back transcripts that reduce endogenous rho expression. We also obtained dominant-negative and neomorphic Star mutations, which have phenotypes similar to those of rho NOVA alleles, as well as dominant-negative Egf-r alleles. The isolation of dominant alleles in several different genes suggests that NOVA mutagenesis should be widely applicable and emerge as an effective tool for generating dominant mutations in genes of unknown function. Section of Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349, USA. Guichard Annabel A Srinivasan Shaila S Zimm Georgianna G Bier Ethan E eng NS 29870 NS NINDS Journal Article

United States Proc Natl Acad Sci U S A 7505876 0 Drosophila Proteins 0 Membrane Proteins 0 Rho protein, Drosophila 0 notch protein 0 rho-2 protein, Drosophila 0 star protein, Drosophila 63231-63-0 RNA EC 2.7.1.112 Receptor, Epidermal Growth Factor IM Alleles Amino Acid Sequence Animal Drosophila Proteins genetics metabolism Drosophila melanogaster embryology genetics metabolism Female Gene Expression Genes, Dominant genetics Genes, Insect genetics Male Membrane Proteins genetics metabolism Molecular Sequence Data Mutagenesis genetics Phenotype RNA genetics metabolism Receptor, Epidermal Growth Factor metabolism Signal Transduction Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Wing embryology physiology FBrf0064739 94032494 8218421 1993 12 02 1993 12 02 2000 12 18

0006-3002 1216 1 1993 Oct 19 An AP-1 binding site in the upstream region of Deb-A is part of a developmentally regulated negative element. 94-104 The Deb-A gene from Drosophila melanogaster encodes a small membrane-associated protein, regulated during development, with peak abundance at 12-15 h of embryogenesis. The cis-acting regulatory elements that control expression of Deb-A during embryogenesis were localized using a somatic transformation assay. The Adh gene of D. melanogaster was used as a 'reporter' gene. The promoterless ADH coding sequence was fused to the 5'-upstream control region of Deb-A. Deletions were introduced into the 5'-region using various restriction sites and Bal31 deletion mutagenesis. A negative regulatory element, or silencer, was localized to a segment 47 base pairs long, between -395 and -442. It is responsible for 80% of the repression of gene expression during late development and reduces levels of Deb-A RNA nearly 5-fold. This negative element is temporally functional. It becomes active after 15 h of embryogenesis and it has no effect on gene expression prior to that. Within this negative element of 47 base pairs, two footprint regions were protected from DNase I digestion by embryonic nuclear extracts: one region contains an AP-1 binding site, but the other footprint is due to unknown element(s). High molecular weight DNA-protein complexes on an oligonucleotide probe spanning the AP-1 binding site were identified in gel retardation assays using partially purified bacterially expressed Djun protein or nuclear extracts from Drosophila embryos. These data suggest that the AP-1 site may be partly responsible for decreasing Deb-A expression during the late embryonic developmental stages of D. melanogaster. Zoology Department, Arizona State University, Tempe 85287. Wang G L GL Goldstein E S ES eng GENBANK L07249 L08443 L19103 M86450 S67478 S67479 S67480 S67481 S67526 S67527 2 S07 RR07112 RR NCRR Journal Article

NETHERLANDS Biochim Biophys Acta 0217513 0 Proto-Oncogene Proteins c-jun EC 3.1.21.1 Deoxyribonuclease I IM Adh Deb-A Amino Acid Sequence Animal Base Sequence Binding Sites Cloning, Molecular Deoxyribonuclease I Drosophila melanogaster embryology genetics Molecular Sequence Data Proto-Oncogene Proteins c-jun genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0123041 20085749 10619029 2000 01 14 2000 01 14 2001 11 02

1097-2765 4 5 1999 Nov Relish, a central factor in the control of humoral but not cellular immunity in Drosophila. 827-37 The NF-kappa B-like Relish gene is complex, with four transcripts that are all located within an intron of the Nmdmc gene. Using deletion mutants, we show that Relish is specifically required for the induction of the humoral immune response, including both antibacterial and antifungal peptides. As a result, the Relish mutants are very sensitive to infection. A single cell of E. cloacae is sufficient to kill a mutant fly, and the mutants show increased susceptibility to fungal infection. In contrast, the blood cell population, the hematopoietic organs, and the phagocytic, encapsulation, and melanization responses are normal. Our results illustrate the importance of the humoral response in Drosophila immunity and demonstrate that Relish plays a key role in this response. Umeå Center for Molecular Pathogenesis, Umeå University, Sweden. Hedengren M M Asling B B Dushay M S MS Ando I I Ekengren S S Wihlborg M M Hultmark D D eng GENBANK AF186073 AF186074 AF186075 AF186076 AF186077 AF186078 AF186079 Journal Article

UNITED STATES Mol Cell 9802571 0 Anti-Infective Agents 0 Antifungal Agents 0 Peptides 0 Transcription Factors 0 relish protein IM Animal Anti-Infective Agents metabolism Antibody Formation genetics immunology Antifungal Agents metabolism Bacteria immunology Cloning, Molecular Drosophila melanogaster cytology genetics immunology microbiology Exons genetics Fungi immunology Genes, Insect genetics physiology Hemocytes immunology Immunity, Cellular genetics immunology Introns genetics Larva cytology immunology microbiology Models, Immunological Molecular Sequence Data Peptides genetics metabolism Phagocytosis immunology Sequence Deletion genetics Signal Transduction Support, Non-U.S. Gov't Transcription Factors genetics immunology Up-Regulation FBrf0125175 20148542 10683183 2000 04 18 2000 04 18 2001 11 02

0950-1991 127 6 2000 Mar The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation. 1315-24 Neurofibromatosis-2 is an inherited disorder characterized by the development of benign schwannomas and other Schwann-cell-derived tumors associated with the central nervous system. The Neurofibromatosis-2 tumor suppressor gene encodes Merlin, a member of the Protein 4.1 superfamily most closely related to Ezrin, Radixin and Moesin. This discovery suggested a novel function for Protein 4.1 family members in the regulation of cell proliferation; proteins in this family were previously thought to function primarily to link transmembrane proteins to underlying cortical actin. To understand the basic cellular functions of Merlin, we are investigating a Drosophila Neurofibromatosis-2 homologue, Merlin. Loss of Merlin function in Drosophila results in hyperplasia of the affected tissue without significant disruptions in differentiation. Similar phenotypes have been observed for mutations in another Protein 4.1 superfamily member in Drosophila, expanded. Because of the phenotypic and structural similarities between Merlin and expanded, we asked whether Merlin and Expanded function together to regulate cell proliferation. In this study, we demonstrate that recessive loss of function of either Merlin or expanded can dominantly enhance the phenotypes associated with mutations in the other. Consistent with this genetic interaction, we determined that Merlin and Expanded colocalize in Drosophila tissues and cells, and physically interact through a conserved N-terminal region of Expanded, characteristic of the Protein 4.1 family, and the C-terminal domain of Merlin. Loss of function of both Merlin and expanded in clones revealed that these proteins function to regulate differentiation in addition to proliferation in Drosophila. Further genetic analyses suggest a role for Merlin and Expanded specifically in Decapentaplegic-mediated differentiation events. These results indicate that Merlin and Expanded function together to regulate proliferation and differentiation, and have implications for understanding the functions of other Protein 4.1 superfamily members. Developmental, Cell and Molecular Biology Group, Duke University, Durham, NC 27708-1000, USA. McCartney B M BM Kulikauskas R M RM LaJeunesse D R DR Fehon R G RG eng F32-NS10224 NS NINDS NS34783 NS NINDS Journal Article

ENGLAND Development 8701744 0 Insect Proteins 0 Membrane Proteins 0 dpp protein, Drosophila 0 expanded protein, Drosophila 0 merlin, Drosophila IM Animal Body Patterning genetics Cell Differentiation genetics Cell Division genetics Drosophila melanogaster cytology genetics growth & development Eye growth & development Female Genes, Insect Genes, Neurofibromatosis 2 Genes, Tumor Suppressor Human Insect Proteins genetics physiology Male Membrane Proteins genetics physiology Phenotype Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tissue Distribution Wing growth & development FBrf0095713 97342670 9199367 1997 07 17 1997 07 17 2000 12 18

0950-1991 124 12 1997 Jun The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila. 2409-19 During animal development cellular differentiation is often preceded by an asymmetric cell division whose polarity is determined by the orientation of the mitotic spindle. In the fruit fly, Drosophila melanogaster, the oocyte differentiates in a 16-cell syncytium that arises from a cystoblast which undergoes 4 synchronous divisions with incomplete cytokinesis. During these divisions, spindle orientation is highly ordered and is thought to impart a polarity to the cyst that is necessary for the subsequent differentiation of the oocyte. Using mutations in the Drosophila cytoplasmic dynein heavy chain gene, Dhc64C, we show that cytoplasmic dynein is required at two stages of oogenesis. Early in oogenesis, dynein mutations disrupt spindle orientation in dividing cysts and block oocyte determination. The localization of dynein in mitotic cysts suggests spindle orientation is mediated by the microtubule motor cytoplasmic dynein. Later in oogenesis, dynein function is necessary for proper differentiation, but does not appear to participate in morphogen localization within the oocyte. These results provide evidence for a novel developmental role for the cytoplasmic dynein motor in cellular determination and differentiation. Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108, USA. McGrail M M Hays T S TS eng Journal Article

ENGLAND Development 8701744 EC 3.6.1.33 Dynein ATPase IM Animal Cell Differentiation genetics Cell Division genetics Cell Polarity Cytoplasm physiology Drosophila melanogaster genetics Dynein ATPase physiology Female Germ Cells physiology Microtubules physiology Mitotic Spindle Apparatus genetics Mutation Oocytes physiology Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. FBrf0034236 81064675 6777047 1981 02 19 1981 02 19 2000 12 18

0092-8674 21 3 1980 Oct The isolation and characterization of Drosophila yolk protein genes. 729-38 We have isolated recombinant DNA clones that contain the genomic sequences coding for the three most abundant proteins in Drosophila eggs, the yolk proteins (YP1, YP2 and YP3). The identity of these cloned genes was established by a two-step procedure. We used the genes to isolate complementary mRNA from total Drosophila RNA; we than showed the in vitro translation products of the isolated mRNAs to be the yolk proteins by comparing their protease digestion products to those of yolk proteins isolated from eggs. An examination of these isolated genes and of their DNA complements in the Drosophila genome showed that each of the three coordinately expressed yolk proteins is encoded by a different single-copy gene. Three genes were cloned; each has a different pattern of restriction endonuclease sites and each appears to be homologous to a different yolk protein mRNA. Southern transfer blots demonstrated that there is only one copy of each gene in the Drosophila genome. Our structural studies have shown that these three genes are not adjacent. In situ hybridization to polytene chromosomes demonstrated, in fact, that the YP3 gene is approximately 1000 kb from the closely spaced YP1 and YP2 genes. Thus, if the coordinate synthesis of the yolk proteins is due to transcriptional control, there must be coordinate control of initiation at two distant sites. Barnett T T Pachl C C Gergen J P JP Wensink P C PC eng Journal Article

UNITED STATES Cell 0413066 0 DNA, Recombinant IM Animal Chromosome Mapping Cloning, Molecular DNA, Recombinant Drosophila melanogaster genetics Female Genes, Structural Male Ovum analysis Support, U.S. Gov't, P.H.S. FBrf0057371 93040226 1418999 1992 12 17 1992 12 17 2000 12 18

0896-6273 9 5 1992 Nov Single amino acid substitutions in EGF-like elements of Notch and Delta modify Drosophila development and affect cell adhesion in vitro. 847-59 Notch locus EGF-like element mutations spl, altering eye development, and AxE2, affecting wing and sensilla development, are modified by mutations at Delta. It is shown that two allele-specific suppressors of spl involve single amino acid substitutions in the 4th (Dlsup5) and 9th (Dlsup4) EGF-like elements of the Delta protein. Cultured cells producing spl or AxE2 aggregate with cells producing wild-type Delta or Dlsup5 protein, and Dlsup5-producing cells adhere to cells producing wild-type Notch protein. However, spl,AxE2, and Dlsup5 are each defective in promoting these cell affinities, as none of the mutant proteins can compete with the corresponding wild-type proteins for formation of cell aggregates. Thus, widely separated EGF-like elements of Notch and Delta appear to participate in functional molecular interactions between the proteins. Dlsup5 does not improve adhesiveness of spl in vitro, so suppression in vivo may involve altered developmental signaling by spl-Dlsup5 complexes, rather than modified cell adhesion. Laboratory of Genetics, Rockefeller University, New York, New York 10021. Lieber T T Wesley C S CS Alcamo E E Hassel B B Krane J F JF Campos-Ortega J A JA Young M W MW eng GENBANK L03725 GM5-25103 GM NIGMS Journal Article

UNITED STATES Neuron 8809320 0 Insect Hormones 0 Membrane Proteins 0 delta protein 0 notch protein 62229-50-9 Epidermal Growth Factor IM Amino Acid Sequence Animal Base Sequence Blotting, Western Cell Adhesion Cell Aggregation Cell Line, Transformed Drosophila melanogaster genetics growth & development Epidermal Growth Factor chemistry genetics Insect Hormones chemistry genetics physiology Membrane Proteins chemistry genetics physiology Molecular Sequence Data Mutagenesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection FBrf0076120 95046887 7958432 1994 11 29 1994 11 29 2002 11 01

0012-1606 165 2 1994 Oct A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. 716-26 We have identified a Drosophila homolog of vertebrate classic cadherins. A monoclonal antibody to Drosophila alpha-catenin (D alpha-catenin) copurifies a 150-kDa glycoprotein (gp150) along with the alpha-catenin. To further characterize this protein, we generated monoclonal antibodies to gp150 and isolated its cDNAs using the antibodies. Predicted sequences of the encoded product revealed that it is a transmembrane protein with similarity to vertebrate classic cadherins, and so we designated this molecule DE-cadherin. The extracellular domain has six cadherin-specific repeats, although the first repeat seems to be cleaved off upon maturation, and the cytoplasmic domain shows significant identity to that of vertebrate classic cadherins. DE-cadherin is distinguishable from its vertebrate counterparts by a large insertion with local sequence similarity to Fat, laminin A chain, Slit, and neurexin I at the proximal region of the extracellular domain. Despite such differences, DE-cadherin is functionally similar to vertebrate classic cadherins. For example, it is associated with alpha-catenin and beta-catenin (Armadillo), and protected from trypsin digestion only in the presence of Ca2+, as is the case for many of classic cadherins. Transfection of S2 cells with the DE-cadherin cDNA enhances their Ca(2+)-dependent cell aggregation. Antibodies to this molecule inhibited aggregation of not only the transfectants but also early embryonic cells. DE-cadherin is concentrated at the apical poles of epithelial cell-cell junctions. All these results suggest that DE-cadherin is a homolog of vertebrate classic cadherins and that the vertebrate and invertebrate share common mechanisms for regulation of cell-cell adhesion. Department of Biophysics, Faculty of Science, Kyoto University, Japan. Oda H H Uemura T T Harada Y Y Iwai Y Y Takeichi M M eng GENBANK D28749 Journal Article

UNITED STATES Dev Biol 0372762 0 Cadherins 0 DNA, Complementary 0 Glycoproteins 0 Proteins 0 armadillo protein, Drosophila IM arm Amino Acid Sequence Animal Cadherins chemistry Cell Adhesion Cell Aggregation Cloning, Molecular Comparative Study DNA, Complementary genetics Drosophila melanogaster chemistry embryology Glycoproteins chemistry genetics Molecular Sequence Data Multigene Family Proteins metabolism Sequence Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't FBrf0105191 99018260 9799737 1998 12 09 1998 12 09 2001 03 23

0960-9822 8 21 1998 Oct 22 Sexual behaviour in Drosophila is irreversibly programmed during a critical period. 1187-90 Sexual differentiation in Drosophila is controlled by a short cascade of regulatory genes, the expression pattern of which determines all aspects of maleness and femaleness, including complex behaviours displayed by males and females [1-3]. One sex-determining gene is transformer (tra), the activity of which is needed for female development. Flies with a female karyotype (XX) but which are mutant for tra develop and behave as males. In such flies, a female phenotype can be restored by a transgene that carries the female-specific cDNA of tra under the control of a heat-shock promoter. This transgene, called hs[trafem], also transforms XY animals into sterile females [4]. When we raised these XX and XY 'females' at 25 degreesC, however, they displayed vigorous male courtship while at the same time, as a result of their female pheromone pattern, they were attractive to males. Intriguingly, their male courtship behaviour was indiscriminately directed towards both females and males. When we forced expression of tra by heat shock, applied during a limited period around puparium formation, male behaviour was abolished and replaced by female behaviour. We conclude that sexual behaviour is irreversibly programmed during a critical period as a result of the activity or inactivity of a single control gene. Zoological Institute University of Zurich Winterthurerstrasse. 190, CH-8057, Zurich, Switzerland. Arthur B I BI Jr Jallon J M JM Caflisch B B Choffat Y Y Nöthiger R R eng Journal Article

ENGLAND Curr Biol 9107782 IM Animal Drosophila melanogaster genetics physiology Female Genes, Insect Infertility, Female genetics Male Models, Biological Phenotype Sex Behavior, Animal Sex Characteristics Support, Non-U.S. Gov't X Chromosome Y Chromosome FBrf0149123 22010444 12015606 2002 05 16 2002 06 10 2002 11 08

0028-0836 417 6886 2002 May 16 Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. 299-304 Although mutations that activate the Hedgehog (Hh) signalling pathway have been linked to several types of cancer, the molecular and cellular basis of Hh's ability to induce tumour formation is not well understood. We identified a mutation in patched (ptc), an inhibitor of Hh signalling, in a genetic screen for regulators of the Retinoblastoma (Rb) pathway in Drosophila. Here we show that Hh signalling promotes transcription of Cyclin E and Cyclin D, two inhibitors of Rb, and principal regulators of the cell cycle during development in Drosophila. Upregulation of Cyclin E expression, accomplished through binding of Cubitus interruptus (Ci) to the Cyclin E promoter, mediates the ability of Hh to induce DNA replication. Upregulation of Cyclin D expression by Hh mediates the distinct ability of Hh to promote cellular growth. The discovery of a direct connection between Hh signalling and principal cell-cycle regulators provides insight into the mechanism by which deregulated Hh signalling promotes tumour formation. Ben May Institute for Cancer Research and Center for Molecular Oncology, The University of Chicago, 924 E. 57th Street, Chicago, Illinois 60637, USA. Duman-Scheel Molly M Weng Li L Xin Shijie S Du Wei W eng Journal Article

England Nature 0410462 0 Cyclin E 0 Cyclins 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Insect Proteins 0 Membrane Proteins 0 Retinoblastoma Protein 0 cubitus interruptus protein 0 cyclin D 0 patched protein, Drosophila 149291-21-4 hedgehog protein, Drosophila 59-14-3 Bromodeoxyuridine IM Animal Bromodeoxyuridine Cell Division Cyclin E genetics Cyclins genetics DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster cytology embryology genetics metabolism Eye cytology embryology metabolism Gene Expression Regulation, Developmental Insect Proteins genetics metabolism Membrane Proteins genetics metabolism Promoter Regions (Genetics) genetics Retinoblastoma Protein metabolism S Phase Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0152308 22223049 12221285 2002 09 18 2002 10 28 2003 03 28

0027-8424 99 19 2002 Sep 17 A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes. 12208-13 Epidermal growth factor receptor (EGFr) is a key mediator of cell communication during animal development and homeostasis. In Drosophila, the signaling event is commonly regulated by the polytopic membrane protein Rhomboid (RHO), which mediates the proteolytic activation of EGFr ligands, allowing the secretion of the active signal. Until very recently, the biochemical function of RHO had remained elusive. It is now believed that Drosophila RHO is the founder member of a previously undescribed family of serine proteases, and that it could be directly responsible for the unusual, intramembranous cleavage of EGFr ligands. Here we show that the function of RHO is conserved in Gram-negative bacteria. AarA, a Providencia stuartii RHO-related protein, is active in Drosophila on the fly EGFr ligands. Vice versa, Drosophila RHO-1 can effectively rescue the bacterium's ability to produce or release the signal that activates density-dependent gene regulation (or quorum sensing). This study provides the first evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell communication and that their biochemical properties could be more similar than previously anticipated. Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden. marco.gallio@sh.se Gallio Marco M Sturgill Gwen G Rather Philip P Kylsten Per P eng Journal Article 2002 09 09

United States Proc Natl Acad Sci U S A 7505876 0 Bacterial Proteins 0 Drosophila Proteins 0 Ligands 0 Membrane Proteins 0 Repressor Proteins 0 Rho protein, Drosophila 0 aarA protein 0 rho-2 protein, Drosophila EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 3.4.21 Serine Endopeptidases IM Amino Acid Sequence Animal Bacterial Proteins genetics metabolism Comparative Study Conserved Sequence Drosophila Proteins genetics metabolism Drosophila melanogaster genetics growth & development metabolism Evolution, Molecular Human Ligands Membrane Proteins genetics metabolism Models, Biological Molecular Sequence Data Phylogeny Providencia genetics metabolism Receptor, Epidermal Growth Factor genetics metabolism Repressor Proteins genetics metabolism Sequence Homology, Amino Acid Serine Endopeptidases genetics metabolism Signal Transduction genetics physiology Support, U.S. Gov't, Non-P.H.S. FBrf0155516 22341472 12454071 2002 11 27 2003 06 10

0016-6731 162 3 2002 Nov Regulation of larval hematopoiesis in Drosophila melanogaster: a role for the multi sex combs gene. 1259-74 Drosophila larval hematopoietic organs produce circulating hemocytes that ensure the cellular host defense by recognizing and neutralizing non-self or noxious objects through phagocytosis or encapsulation and melanization. Hematopoietic lineage specification as well as blood cell proliferation and differentiation are tightly controlled. Mutations in genes that regulate lymph gland cell proliferation and hemocyte numbers in the body cavity cause hematopoietic organ overgrowth and hemocyte overproliferation. Occasionally, mutant hemocytes invade self-tissues, behaving like neoplastic malignant cells. Two alleles of the Polycomb group (PcG) gene multi sex combs (mxc) were previously isolated as such lethal malignant blood neoplasm mutations. PcG genes regulate Hox gene expression in vertebrates and invertebrates and participate in mammalian hematopoiesis control. Hence we investigated the need for mxc in Drosophila hematopoietic organs and circulating hemocytes. We show that mxc-induced hematopoietic hyperplasia is cell autonomous and that mxc mainly controls plasmatocyte lineage proliferation and differentiation in lymph glands and circulating hemocytes. Loss of the Toll pathway, which plays a similar role in hematopoiesis, counteracted mxc hemocyte proliferation but not mxc hemocyte differentiation. Several PcG genes tested in trans had no effects on mxc hematopoietic phenotypes, whereas the trithorax group gene brahma is important for normal and mutant hematopoiesis control. We propose that mxc provides one of the regulatory inputs in larval hematopoiesis that control normal rates of plasmatocyte and crystal lineage proliferation as well as normal rates and timing of hemocyte differentiation. Centre de Génétique Moléculaire du CNRS UPR 2167, F-91198 Gif sur Yvette Cedex, France. Remillieux-Leschelle Nathalie N Santamaria Pedro P Randsholt Neel B NB eng Journal Article

United States Genetics 0374636 IM Animal Cell Division Drosophila melanogaster genetics physiology Hematopoiesis genetics physiology Larva genetics physiology Lymphatic System growth & development physiology Lymphocytes cytology Support, Non-U.S. Gov't FBrf0082297 95246734 7729418 1995 05 30 1995 05 30 2001 11 02

0261-4189 14 7 1995 Apr 3 An amino acid substitution in the Drosophila hopTum-l Jak kinase causes leukemia-like hematopoietic defects. 1412-20 Proteins of the Jak family of non-receptor kinases play important roles in mammalian hematopoietic signal transduction. They mediate the cellular response to a wide range of cytokines and growth factors. A dominant mutation in a Drosophila Jak kinase, hopscotchTumorous-lethal (hopTum-l), causes hematopoietic defects. Here we conduct a molecular analysis of hopTum-l. We demonstrate that the hopTum-l hematopoietic phenotype is caused by a single amino acid substitution of glycine to glutamic acid at residue 341. We generate a true revertant of the hopTum-l mutation, in which both the molecular lesion and the mutant hematopoietic phenotype revert back to wild type. We also examine the effects of the G341E substitution in transgenic flies. The results indicate that a mutant Jak kinase can cause leukemia-like abnormalities. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Luo H H Hanratty W P WP Dearolf C R CR eng HL 48823 HL NHLBI Journal Article

ENGLAND EMBO J 8208664 0 DNA Primers EC 2.7.1.- Hop protein EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal Animals, Genetically Modified Base Sequence Crosses, Genetic DNA Primers Drosophila melanogaster enzymology genetics physiology Female Genes, Lethal Genotype Hematopoiesis genetics physiology Heterozygote Larva Leukemia, Experimental Male Molecular Sequence Data Mutagenesis, Site-Directed Point Mutation Protein-Tyrosine Kinase biosynthesis genetics metabolism Pupa Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0130188 20453808 10996811 2000 10 25 2000 12 07 2003 06 16

0960-9822 10 18 2000 Sep 21 Sex determination: co-opted signals determine gender. R682-4 The Drosophila JAK-STAT pathway and its ligand Unpaired are required for a wide range of developmental processes. Recent results have identified Unpaired as an activator of sex-lethal and revealed a new role for the JAK-STAT pathway in sex determination. Hughes Medical Institute, Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. Zeidler M P MP Perrimon N N eng Journal Article

ENGLAND Curr Biol 9107782 0 DNA-Binding Proteins 0 Glycoproteins 0 Insect Hormones 0 RNA-Binding Proteins 0 Sxl protein, Drosophila 0 Trans-Activators 0 gamma-activated factor, 91-kD 0 outstretched protein, Drosophila EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal DNA-Binding Proteins metabolism Drosophila melanogaster genetics physiology Female Gene Expression Regulation Glycoproteins genetics metabolism Insect Hormones genetics metabolism Male Protein-Tyrosine Kinase metabolism RNA-Binding Proteins genetics metabolism Sex Chromosomes genetics metabolism Sex Determination (Genetics) Signal Transduction Trans-Activators metabolism FBrf0059051 93268301 8497266 1993 06 23 1993 06 23 2000 12 18

0270-7306 13 6 1993 Jun Regulation of the proneural gene achaete by helix-loop-helix proteins. 3514-21 The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo. Centro de Biología Molecular Severo Ochoa, Madrid, Spain. Martínez C C Modolell J J Garrell J J eng Journal Article

UNITED STATES Mol Cell Biol 8109087 0 DNA-Binding Proteins 0 Oligodeoxyribonucleotides 0 Recombinant Fusion Proteins 0 emc protein EC 3.2.1.23 beta-Galactosidase IM ac emc sc Amino Acid Sequence Animal Base Sequence DNA-Binding Proteins genetics metabolism Drosophila melanogaster genetics physiology Gene Expression Regulation Genes, Structural Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides Polymerase Chain Reaction Promoter Regions (Genetics) Recombinant Fusion Proteins metabolism Support, Non-U.S. Gov't Transcription, Genetic beta-Galactosidase genetics metabolism FBrf0083777 96129283 8582615 1996 03 20 1996 03 20 2003 06 16

0016-6731 141 3 1995 Nov Genomic regions required for morphogenesis of the Drosophila embryonic midgut. 1087-100 The Drosophila midgut is an excellent system for studying the cell migration, cell-cell communication, and morphogenetic events that occur in organ formation. Genes representative of regulatory gene families common to all animals, including homeotic, TGF beta, and Wnt genes, play roles in midgut development. To find additional regulators of midgut morphogenesis, we screened a set of genomic deficiencies for midgut phenotypes. Fifteen genomic intervals necessary for proper midgut morphogenesis were identified, three contain genes already known to act in the midgut. Three other genomic regions are required for formation of the endoderm or visceral mesoderm components of the midgut. Nine regions are required for proper formation of the midgut constrictions. The E75 ecdysone-induced gene, which encodes a nuclear receptor superfamily member, is the relevant gene in one region and is essential for proper formation of midgut constrictions. E75 acts downstream of the previously known constriction regulators or in parallel. Temporal hormonal control may therefore work in conjunction with spatial regulation by the homeotic genes in midgut development. Another genomic region is required to activate transcription of the homeotic genes Antp and Scr specifically in visceral mesoderm. The genomic regions identified by this screen provide a map to novel midgut development regulators. Department of Developmental Biology, Stanford University School of Medicine, California 94305-5427, USA. Bilder D D Scott M P MP eng 18163 PHS Journal Article

UNITED STATES Genetics 0374636 0 Antennapedia homeodomain protein 0 DNA-Binding Proteins 0 GmE75 receptor 0 Insect Hormones 0 Receptors, Steroid 0 Sex combs reduced protein, Drosophila IM Animal DNA-Binding Proteins genetics physiology Drosophila melanogaster embryology genetics Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Insect Hormones genetics physiology Intestines embryology Morphogenesis genetics Organ Specificity Phenotype Receptors, Steroid genetics physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0082203 96120242 7498743 1996 01 17 1996 01 17 2000 12 18

0016-6731 140 2 1995 Jun Regulatory regions of the homeotic gene proboscipedia are sensitive to chromosomal pairing. 643-58 We have identified regulatory regions of the homeotic gene proboscipedia that are capable of repressing a linked white minigene in a manner that is sensitive to chromosomal pairing. Normally, the eye color of transformants containing white in a P-element vector is affected by the number of copies of the transgene; homozygous flies have darker eyes than heterozygotes. However, we found that flies homozygous for select pb DNA-containing transgenes had lighter eyes than heterozygotes. Several pb DNA fragments are capable of causing this pairing sensitive (PS) negative regulation of white. Two fragments in the upstream DNA of pb, 0.58 and 0.98 kb, are PS; additionally, two PS sites are located in the second intron, including a 0.5-kb region and 49-bp sequence. This phenotype is not observed when two PS sites are located at different chromosomal insertion sites (in trans-heterozygous transgenic animals), indicating that the pb-DNA-mediated repression of white is dependent on the pairing or proximity of the PS regions. The observed phenomenon is similar to transvection in which certain alleles of a gene can complement each other, but only when homologous chromosomes are paired. Interestingly, the intronic PS regions contain positive regulatory sequences for pb, whereas the upstream PS sites contain pb negative regulatory elements. Howard Hughes Medical Institute, Department of Biology, Indiana University, Bloomington 47405, USA. Kapoun A M AM Kaufman T C TC eng GM24299 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Oligonucleotide Probes 0 Recombinant Fusion Proteins IM Alleles Animal Base Sequence Drosophila melanogaster anatomy & histology genetics Eye ultrastructure Eye Color genetics Genes, Homeobox Germ-Line Mutation Linkage (Genetics) Microscopy, Electron, Scanning Models, Genetic Molecular Sequence Data Oligonucleotide Probes Recombinant Fusion Proteins genetics Regulatory Sequences, Nucleic Acid Sequence Deletion Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Suppression, Genetic FBrf0107310 99168778 10071220 1999 04 07 1999 04 07 2002 11 01

0026-8925 261 1 1999 Feb Mutations in the predicted aspartyl tRNA synthetase of Drosophila are lethal and function as dosage-sensitive maternal modifiers of the sex determination gene Sex-lethal. 142-51 Stable activation of the Drosophila sex determination gene Sex-lethal in the female embryo is a multistep process. Early in embryogenesis Sex-lethal is regulated at the level of transcription, and then later in embryogenesis Sex-lethal regulation switches to an autoregulatory RNA splicing mechanism. Previous studies have shown that successful activation of Sxl requires both maternally and zygotically provided gene products, many of which are essential for viability and have other, non-sex specific functions. Using a screen for dosage-sensitive modifiers we identified a new maternally expressed gene, l(2)49Db, as a likely participant in Sxl activation. We show that the establishment of the Sxl autoregulatory splicing loop, but not the earlier steps in Sxl activation, is sensitive to the maternal dosage of l(2)49Db. We further demonstrate that l(2)49Db encodes an aspartyl tRNA synthetase. Finally we present evidence that this effect is indirect, by demonstrating that mutations in tryptophanyl tRNA synthetase are also dosage-sensitive maternal modifiers of Sex-lethal. These data suggest that stable activation of Sex-lethal in the embryo may be particularly sensitive to perturbation of the translational machinery. Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4955, USA. Stitzinger S M SM Pellicena-Palle A A Albrecht E B EB Gajewski K M KM Beckingham K M KM Salz H K HK eng GENBANK AF113612 Journal Article

GERMANY Mol Gen Genet 0125036 0 DNA, Complementary 0 RNA-Binding Proteins 0 Ribonucleoprotein, U1 Small Nuclear 0 SNF protein 0 Sxl protein, Drosophila EC 6.1.1. Amino Acyl-tRNA Ligases EC 6.1.1.12 Aspartate-tRNA Ligase IM S Amino Acid Sequence Amino Acyl-tRNA Ligases genetics Animal Aspartate-tRNA Ligase genetics Cloning, Molecular DNA, Complementary chemistry genetics Drosophila melanogaster enzymology genetics Embryo, Nonmammalian metabolism Female Gene Dosage Gene Expression Regulation, Developmental Genes, Lethal genetics Genes, Structural, Insect genetics Molecular Sequence Data Mutation Promoter Regions (Genetics) RNA Splicing RNA-Binding Proteins genetics Ribonucleoprotein, U1 Small Nuclear genetics Sequence Alignment Sequence Analysis, DNA Sequence Homology, Amino Acid Sex Determination (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Transcription, Genetic Non-programmatic FBrf0144841 21818631 11830571 2002 02 06 2002 03 04 2003 06 16

0950-1991 129 3 2002 Feb JAK signaling is somatically required for follicle cell differentiation in Drosophila. 705-17 Janus kinase (JAK) pathway activity is an integral part of signaling through a variety of ligands and receptors in mammals. The extensive re-utilization and pleiotropy of this pathway in vertebrate development is conserved in other animals as well. In Drosophila melanogaster, JAK signaling has been implicated in embryonic pattern formation, sex determination, larval blood cell development, wing venation, planar polarity in the eye, and formation of other adult structures. Here we describe several roles for JAK signaling in Drosophila oogenesis. The gene for a JAK pathway ligand, unpaired, is expressed specifically in the polar follicle cells, two pairs of somatic cells at the anterior and posterior poles of the developing egg chamber. Consistent with unpaired expression, reduced JAK pathway activity results in the fusion of developing egg chambers. A primary defect of these chambers is the expansion of the polar cell population and concomitant loss of interfollicular stalk cells. These phenotypes are enhanced by reduction of unpaired activity, suggesting that Unpaired is a necessary ligand for the JAK pathway in oogenesis. Mosaic analysis of both JAK pathway transducers, hopscotch and Stat92E, reveals that JAK signaling is specifically required in the somatic follicle cells. Moreover, JAK activity is also necessary for the initial commitment of epithelial follicle cells. Many of these roles are in common with, but distinct from, the known functions of Notch signaling in oogenesis. Consistent with these data is a model in which Notch signaling determines a pool of cells to be competent to adopt stalk or polar fate, while JAK signaling assigns specific identity within that competent pool. University of Kentucky, T. H. Morgan School of Biological Sciences, 101 Morgan Building, Lexington, KY 40506, USA. McGregor Jennifer R JR Xi Rongwen R Harrison Douglas A DA eng Journal Article

England Development 8701744 0 Drosophila Proteins 0 Glycoproteins 0 outstretched protein, Drosophila EC 2.7.1.- Hop protein EC 2.7.1.112 Protein-Tyrosine Kinase IM Animal Cell Compartmentation Cell Differentiation Drosophila cytology physiology Drosophila Proteins isolation & purification Enzyme Activation Epithelial Cells cytology Female Glycoproteins isolation & purification Models, Biological Mutation Oogenesis physiology Ovarian Follicle cytology physiology Phenotype Protein-Tyrosine Kinase isolation & purification metabolism Signal Transduction Support, U.S. Gov't, Non-P.H.S. FBrf0132342 21100346 11156990 2001 02 22 2001 05 24

0016-6731 157 2 2001 Feb Complex organization of promoter and enhancer elements regulate the tissue- and developmental stage-specific expression of the Drosophila melanogaster Gld gene. 699-716 The Drosophila melanogaster Gld gene has multiple and diverse developmental and physiological functions. We report herein that interactions among proximal promoter elements and a cluster of intronically located enhancers and silencers specify the complex regulation of Gld that underlies its diverse functions. Gld expression in nonreproductive tissues is largely determined by proximal promoter elements with the exception of the embryonic labium where Gld is activated by an enhancer within the first intron. A nuclear protein, GPAL, has been identified that binds the Gpal elements in the proximal promoter region. Regulation of Gld in the reproductive organs is particularly complex, involving interactions among the Gpal proximal promoter elements, a unique TATA box, three distinct enhancer types, and one or more silencer elements. The three somatic reproductive organ enhancers each activate expression in male and female pairs of reproductive organs. One of these pairs, the male ejaculatory duct and female oviduct, are known to be developmentally homologous. We report evidence that the other two pairs of organs are developmentally homologous as well. A comprehensive model to explain the full developmental regulation of Gld and its evolution is presented. Department of Molecular Biology, Vanderbilt University, Nashville, TN 37205, USA. Keplinger B L BL Guo X X Quine J J Feng Y Y Cavener D R DR eng GM-34170 GM NIGMS Journal Article

United States Genetics 0374636 0 Plasmids EC 1.1.1. Glucose Dehydrogenases EC 1.1.1.47 glucose dehydrogenase EC 3.2.1.23 beta-Galactosidase IM Animal Base Sequence Cell Nucleus metabolism Drosophila melanogaster genetics Enhancer Elements (Genetics) Evolution, Molecular Female Gene Expression Regulation, Developmental Glucose Dehydrogenases chemistry genetics Introns Male Models, Biological Models, Genetic Molecular Sequence Data Mutagenesis Mutagenesis, Site-Directed Plasmids metabolism Promoter Regions (Genetics) Protein Binding Sex Factors Support, U.S. Gov't, P.H.S. Time Factors Tissue Distribution beta-Galactosidase metabolism FBrf0148977 22060500 12065414 2002 06 14 2002 08 29 2003 06 16

0261-4189 21 12 2002 Jun 17 Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. 3009-18 Drosophila provides a powerful genetic model for studying the in vivo regulation of cell death. In our large-scale gain-of-function screen, we identified Eiger, the first invertebrate tumor necrosis factor (TNF) superfamily ligand that can induce cell death. Eiger is a type II transmembrane protein with a C-terminal TNF homology domain. It is predominantly expressed in the nervous system. Genetic evidence shows that Eiger induces cell death by activating the Drosophila JNK pathway. Although this cell death process is blocked by Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), it does not require caspase activity. We also show genetically that Eiger is a physiological ligand for the Drosophila JNK pathway. Our findings demonstrate that Eiger can initiate cell death through an IAP-sensitive cell death pathway via JNK signaling. Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Igaki Tatsushi T Kanda Hiroshi H Yamamoto-Goto Yuki Y Kanuka Hirotaka H Kuranaga Erina E Aigaki Toshiro T Miura Masayuki M eng GENBANK AB073865 Journal Article

England EMBO J 8208664 0 Drosophila Proteins 0 Insect Proteins 0 Ligands 0 MAP Kinase Signaling System 0 Membrane Proteins 0 Peptides 0 Tumor Necrosis Factor 0 eiger protein, Drosophila 0 inhibitor-of-apoptosis protein 0 reaper peptide, Drosophila EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.10.- c-Jun amino-terminal kinase IM Amino Acid Sequence Animal Apoptosis physiology Drosophila Proteins chemistry genetics metabolism Drosophila melanogaster anatomy & histology genetics growth & development physiology Embryo anatomy & histology physiology Genes, Insect In Situ Hybridization Insect Proteins physiology Ligands MAP Kinase Signaling System physiology Membrane Proteins chemistry genetics metabolism Mitogen-Activated Protein Kinases metabolism Molecular Sequence Data Multigene Family Peptides genetics metabolism Phenotype Photoreceptors, Invertebrate growth & development Sequence Alignment Support, Non-U.S. Gov't Tumor Necrosis Factor genetics metabolism FBrf0139770 21468410 11584269 2001 10 03 2001 12 04 2003 05 30

1465-7392 3 10 2001 Oct Spatial control of the actin cytoskeleton in Drosophila epithelial cells. 883-90 The actin cytoskeleton orders cellular space and transduces many of the forces required for morphogenesis. Here we combine genetics and cell biology to identify genes that control the polarized distribution of actin filaments within the Drosophila follicular epithelium. We find that profilin and cofilin regulate actin-filament formation throughout the cell cortex. In contrast, CAP-a Drosophila homologue of Adenylyl Cyclase Associated Proteins-functions specifically to limit actin-filament formation catalysed by Ena at apical cell junctions. The Abl tyrosine kinase also collaborates in this process. We therefore propose that CAP, Ena and Abl act in concert to modulate the subcellular distribution of actin filaments in Drosophila. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. bbaum@rascal.med.harvard.edu Baum B B Perrimon N N eng Journal Article

England Nat Cell Biol 100890575 0 Actins 0 Cell Cycle Proteins 0 DNA-Binding Proteins 0 Insect Proteins 0 adenyl cyclase-associated protein 0 ena protein IM Actins genetics metabolism Animal Cell Cycle Proteins metabolism Cell Polarity genetics DNA-Binding Proteins metabolism Drosophila melanogaster cytology genetics Epithelial Cells metabolism Female Genes, abl Insect Proteins metabolism Microfilaments metabolism ultrastructure Microscopy, Fluorescence Models, Biological Ovarian Follicle cytology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0156039 22364107 12461171 2002 12 11 2003 01 28

0027-8424 99 25 2002 Dec 10 Near-neutrality in evolution of genes and gene regulation. 16134-7 The nearly neutral theory contends that the interaction of drift and selection is important and occurs at various levels, including synonymous and nonsynonymous substitutions in protein coding regions and sequence turnover of regulatory elements. Recent progress of the theory is reviewed, and the interaction between drift and selection is suggested to differ at these different levels. Weak selective force on synonymous changes is stable, whereas its consequence on nonsynonymous changes depends on environmental factors. Selection on differentiation of regulatory elements is even more dependent on environmental factors than on amino acid changes. Of particular significance is the role of drift in the evolution of gene regulation that directly participates in morphological evolution. The range of near neutrality depends on the effective size of the population that is influenced by selected linked loci. In addition to the effective population size, molecular chaperones such as heat shock protein 90 have significant effects on the range of near neutrality. National Institute of Genetics, Mishima 411-8540, Japan. tohta@lab.nig.ac.jp Ohta Tomoko T eng Journal Article 2002 12 02

United States Proc Natl Acad Sci U S A 7505876 0 Molecular Chaperones IM Amino Acid Substitution Animal Arabidopsis genetics Drosophila genetics Drosophila melanogaster genetics Evolution, Molecular Gene Expression Regulation Genes Genetic Drift Linkage (Genetics) Models, Genetic Molecular Chaperones physiology Regulatory Sequences, Nucleic Acid Selection (Genetics) Species Specificity FBrf0144898 21850432 11861561 2002 03 07 2002 05 24 2002 10 21

0016-6731 160 2 2002 Feb The Drosophila gene taranis encodes a novel trithorax group member potentially linked to the cell cycle regulatory apparatus. 547-60 Genes of the Drosophila Polycomb and trithorax groups (PcG and trxG, respectively) influence gene expression by modulating chromatin structure. Segmental expression of homeotic loci (HOM) initiated in early embryogenesis is maintained by a balance of antagonistic PcG (repressor) and trxG (activator) activities. Here we identify a novel trxG family member, taranis (tara), on the basis of the following criteria: (i) tara loss-of-function mutations act as genetic antagonists of the PcG genes Polycomb and polyhomeotic and (ii) they enhance the phenotypic effects of mutations in the trxG genes trithorax (trx), brahma (brm), and osa. In addition, reduced tara activity can mimic homeotic loss-of-function phenotypes, as is often the case for trxG genes. tara encodes two closely related 96-kD protein isoforms (TARA-alpha/-beta) derived from broadly expressed alternative promoters. Genetic and phenotypic rescue experiments indicate that the TARA-alpha/-beta proteins are functionally redundant. The TARA proteins share evolutionarily conserved motifs with several recently characterized mammalian nuclear proteins, including the cyclin-dependent kinase regulator TRIP-Br1/p34(SEI-1), the related protein TRIP-Br2/Y127, and RBT1, a partner of replication protein A. These data raise the possibility that TARA-alpha/-beta play a role in integrating chromatin structure with cell cycle regulation. Centre de Biologie du Développement, Université Paul Sabatier, 31062 Toulouse Cedex, France. Calgaro Stéphane S Boube Muriel M Cribbs David L DL Bourbon Henri-Marc HM eng GENBANK AF227211 AF227212 Journal Article

United States Genetics 0374636 0 Cell Cycle Proteins 0 DNA, Complementary 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Homeodomain Proteins 0 Protein Isoforms 0 RNA, Messenger 0 Transcription Factors 0 proboscipedia protein, Drosophila 0 taranis protein, Drosophila 0 trithorax gene product IM Amino Acid Sequence Animal Base Sequence Cell Cycle genetics physiology Cell Cycle Proteins genetics DNA, Complementary genetics DNA-Binding Proteins genetics Drosophila Proteins genetics Drosophila melanogaster cytology genetics Exons genetics Gene Expression Regulation genetics physiology Genes, Insect Homeodomain Proteins genetics physiology Molecular Sequence Data Protein Isoforms genetics physiology RNA, Messenger genetics Sequence Analysis, DNA Support, Non-U.S. Gov't Transcription Factors genetics physiology FBrf0074771 95009532 7925007 1994 11 01 1994 11 01 2001 11 02

0950-1991 120 7 1994 Jul Drosophila virilis oskar transgenes direct body patterning but not pole cell formation or maintenance of mRNA localization in D. melanogaster. 2027-37 The Drosophila melanogaster gene oskar is required for both posterior body patterning and germline formation in the early embryo; precisely how oskar functions is unknown. The oskar transcript is localized to the posterior pole of the developing oocyte, and oskar mRNA and protein are maintained at the pole through early embryogenesis. The posterior maintenance of oskar mRNA is dependent upon the presence of oskar protein. We have cloned and characterized the Drosophila virilis oskar homologue, virosk, and examined its activity as a transgene in Drosophila melanogaster flies. We find that the cis-acting mRNA localization signals are conserved, although the virosk transcript also transiently accumulates at novel intermediate sites. The virosk protein, however, shows substantial differences from oskar: while virosk is able to rescue body patterning in a D. melanogaster oskar- background, it is impaired in both mRNA maintenance and pole cell formation. Furthermore, virosk induces a dominant maternal-effect lethality when introduced into a wild-type background, and interferes with the posterior maintenance of the endogenous oskar transcript in early embryogenesis. Our data suggest that virosk protein is unable to anchor at the posterior pole of the early embryo; this defect could account for all of the characteristics of virosk mentioned above. Our observations support a model in which oskar protein functions both by nucleating the factors necessary for the activation of the posterior body patterning determinant and the germ cell determinant, and by anchoring these factors to the posterior pole of the embryo. While the posterior body patterning determinant need not be correctly localized to provide body patterning activity, the germ cell determinant may need to be highly concentrated adjacent to the cortex in order to direct pole cell formation. Department of Biological Sciences, Stanford University, CA 94305-5020. Webster P J PJ Suen J J Macdonald P M PM eng GENBANK L22556 Journal Article

ENGLAND Development 8701744 0 RNA, Messenger IM Amino Acid Sequence Animal Animals, Genetically Modified genetics Base Sequence Comparative Study Drosophila genetics Drosophila melanogaster embryology Germ Cells physiology Immunohistochemistry In Situ Hybridization Molecular Sequence Data RNA, Messenger metabolism Sequence Homology FBrf0092648 97209479 9056779 1997 04 07 1997 04 07 2003 03 28

0950-1991 124 5 1997 Mar Two-step induction of chordotonal organ precursors in Drosophila embryogenesis. 1045-53 The chordotonal (Ch) organ, an internal stretch receptor located in the subepidermal layer, is one of the major sensory organs in the peripheral nervous system of Drosophila melanogaster. Although the cell lineage of the Ch organ has been well characterized in many studies, the determination machinery of Ch organ precursor cells (COPs) remains largely unresolved. Here we report that the rhomboid (rho) gene and the activity of the Drosophila EGF receptor (DER) signaling pathway are necessary to induce specifically three of the eight COPs in an embryonic abdominal hemisegment. The cell-lineage analysis of COPs using the yeast flpase (flp/FRT) method indicated that each of the eight COPs originated from an individual undifferentiated ectodermal cell. The eight COPs in each abdominal hemisegment seemed to be determined by a two-phase induction: first, five COPs are determined by the action of the proneural gene atonal and neurogenic genes. Subsequently, these five COPs start to express the rho gene, and rho activates the DER-signaling pathway in neighboring cells and induces argos expression. Three of these argos-expressing cells differentiate into the three remaining COPs and they prevent neighboring cells from becoming extra COPs. Department of Molecular Neurobiology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan. Okabe M M Okano H H eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Eye Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Rho protein, Drosophila 0 ato protein 0 rho-2 protein, Drosophila 147954-53-8 gil protein IM Animal DNA-Binding Proteins physiology Drosophila melanogaster embryology Eye Proteins metabolism Helix-Loop-Helix Motifs In Situ Hybridization Mechanoreceptors embryology Membrane Proteins genetics Models, Molecular Nerve Tissue Proteins metabolism Signal Transduction Support, Non-U.S. Gov't FBrf0135682 21234973 11336671 2001 05 04 2001 05 31

0092-8674 105 2 2001 Apr 20 Drosophila wingless and pair-rule transcripts localize apically by dynein-mediated transport of RNA particles. 209-19 Asymmetric mRNA localization targets proteins to their cytoplasmic site of function. We have elucidated the mechanism of apical localization of wingless and pair-rule transcripts in the Drosophila blastoderm embryo by directly visualizing intermediates along the entire path of transcript movement. After release from their site of transcription, mRNAs diffuse within the nucleus and are exported to all parts of the cytoplasm, regardless of their cytoplasmic destinations. Endogenous and injected apical RNAs assemble selectively into cytoplasmic particles that are transported apically along microtubules. Cytoplasmic dynein is required for correct localization of endogenous transcripts and apical movement of injected RNA particles. We propose that dynein-dependent movement of RNA particles is a widely deployed mechanism for mRNA localization. Wellcome Trust Centre for Cell Biology, ICMB, University of Edinburgh, King's Buildings, Edinburgh EH9 3JR, Scotland, United Kingdom. Wilkie G S GS Davis I I eng Journal Article

United States Cell 0413066 0 Antineoplastic Agents, Phytogenic 0 DNA-Binding Proteins 0 Fluorescent Dyes 0 Homeodomain Proteins 0 Proto-Oncogene Proteins 0 RNA, Messenger 0 Runt protein 0 fushi tarazu protein 117758-26-6 wingless protein, Drosophila 477-30-5 Demecolcine EC 3.6.1.33 Dynein ATPase IM Active Transport, Cell Nucleus drug effects physiology Animal Antineoplastic Agents, Phytogenic pharmacology Cell Polarity DNA-Binding Proteins metabolism Demecolcine pharmacology Drosophila melanogaster physiology Dynein ATPase genetics metabolism Embryo, Nonmammalian cytology physiology Fluorescent Dyes metabolism Homeodomain Proteins metabolism In Situ Hybridization, Fluorescence Microinjections Microscopy, Fluorescence Microtubules metabolism Proto-Oncogene Proteins metabolism RNA, Messenger metabolism Support, Non-U.S. Gov't Time Factors FBrf0079894 95229050 7713421 1995 05 18 1995 05 18 2002 11 01

0016-6731 139 2 1995 Feb Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing. 631-48 Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle "on" vs. "off" reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. "Male-lethal" (SxlM) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, SxlM haplo-X animals (chromosomal males) die because of improper dosage compensation, and SxlM chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Five independent spontaneous SxlM alleles were shown previously to be transposon insertions into what was subsequently found to be the region of regulated sex-specific Sxl RNA splicing. We show that these five alleles represent three different mutant types: SxlM1, SxlM3, and SxlM4. SxlM1 is an insertion of a roo element 674 bp downstream of the translation-terminating male-specific exon. SxlM3 is an insertion of a hobo transposon (not 297 as previously reported) into the 3' splice site of the male exon, and SxlM4 is an insertion of a novel transposon into the male-specific exon itself. We show that these three gain-of-function mutants differ considerably in their ability to bypass the sex determination signal, with SxlM4 being the strongest and SxlM1 the weakest. This difference is also reflected in effects of these mutations on sex-specific RNA splicing and on the rate of appearance of SXL protein in male embryos. Transcript analysis of double-mutant male-viable SxlM derivatives in which the SxlM insertion is cis to loss-of-function mutations, combined with other results reported here, indicates that the constitutive character of these SxlM alleles is a consequence of an alteration of the structure of the pre-mRNA that allows some level of female splicing to occur even in the absence of functional SXL protein. Surprisingly, however, most of the constitutive character of SxlM alleles appears to depend on the mutant alleles' responsiveness, perhaps greater than wild-type, to the autoregulatory splicing activity of the wild-type SXL proteins they produce. Department of Biology, Princeton University, New Jersey 08544, USA. Bernstein M M Lersch R A RA Subrahmanyan L L Cline T W TW eng GENBANK X80025 GM23468 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 DNA Transposable Elements 0 Insect Hormones 0 RNA Precursors 0 RNA, Messenger 0 Sxl protein, Drosophila IM Sxl Amino Acid Sequence Animal Base Sequence Cloning, Molecular DNA Mutational Analysis DNA Transposable Elements genetics Dosage Compensation (Genetics) Drosophila melanogaster embryology genetics Female Genes, Insect physiology Genes, Lethal physiology Genes, Switch Insect Hormones genetics Male Molecular Sequence Data Mutation physiology RNA Precursors analysis RNA Splicing RNA, Messenger analysis Sex Differentiation genetics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0099763 98072490 9409832 1998 02 19 1998 02 19 2000 12 18

0016-6731 147 4 1997 Dec P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: mutations affecting embryonic PNS development. 1723-41 To identify novel genes and to isolate tagged mutations in known genes that are required for the development of the peripheral nervous system (PNS), we have screened a novel collection of 2460 strains carrying lethal or semilethal P element insertions on the third chromosome. Monoclonal antibody 22C10 was used as a marker to visualize the embryonic PNS. We identified 109 mutant strains that exhibited reproducible phenotypes in the PNS. Cytological and genetic analyses of these strains indicated that 87 mutations affect previously identified genes: tramtrack (n = 18 alleles), string (n = 15), cyclin A (n = 13), single-minded (n = 13), Delta (n = 9), neuralized (n = 4), pointed (n = 4), extra macrochaetae (n = 4), prospero (n = 3), tartan (n = 2), and pebble (n = 2). In addition, 13 mutations affect genes that we identified recently in a chemical mutagenesis screen designed to isolate similar mutants: hearty (n = 3), dorsotonals (n = 2), pavarotti (n = 2), sanpodo (n = 2), dalmatian (n = 1), missensed (n = 1), senseless (n = 1), and sticky ch1 (n = 1). The remaining nine mutations define seven novel complementation groups. The data presented here demonstrate that this collection of P elements will be useful for the identification and cloning of novel genes on the third chromosome, since >70% of mutations identified in the screen are caused by the insertion of a P element. A comparison between this screen and a chemical mutagenesis screen undertaken earlier highlights the complementarity of the two types of genetic screens. Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. Salzberg A A Prokopenko S N SN He Y Y Tsai P P Pál M M Maróy P P Glover D M DM Deák P P Bellen H J HJ eng Journal Article

UNITED STATES Genetics 0374636 0 Antibodies, Monoclonal 0 DNA Transposable Elements IM Alleles Animal Antibodies, Monoclonal metabolism Axons Chromosome Mapping Chromosomes DNA Transposable Elements Drosophila melanogaster embryology genetics Gene Expression Genes, Insect Lac Operon Mutagenesis Neurons metabolism Peripheral Nervous System cytology embryology Phenotype Support, Non-U.S. Gov't FBrf0111967 20042294 10572049 2000 01 21 2000 01 21 2003 03 28

0950-1991 126 24 1999 Dec A temporal switch in DER signaling controls the specification and differentiation of veins and interveins in the Drosophila wing. 5739-47 The Drosophila EGF receptor (DER) is required for the specification of diverse cell fates throughout development. We have examined how the activation of DER controls the development of vein and intervein cells in the Drosophila wing. The data presented here indicate that two distinct events are involved in the determination and differentiation of wing cells. (1) The establishment of a positive feedback amplification loop, which drives DER signaling in larval stages. At this time, rhomboid (rho), in combination with vein, initiates and amplifies the activity of DER in vein cells. (2) The late downregulation of DER activity. At this point, the inactivation of MAPK in vein cells is necessary for the maintenance of the expression of decapentaplegic (dpp) and becomes essential for vein differentiation. Together, these temporal and spatial changes in the activity of DER constitute an autoregulatory network that controls the definition of vein and intervein cell types. Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK. emblanco@trasto.cbm.uam.es Martín-Blanco E E Roch F F Noll E E Baonza A A Duffy J B JB Perrimon N N eng Journal Article

ENGLAND Development 8701744 0 Eye Proteins 0 Insect Proteins 0 Membrane Proteins 0 Nerve Tissue Proteins 0 Receptors, Invertebrate Peptide 0 Rho protein, Drosophila 0 dpp protein, Drosophila 0 epidermal growth factor receptor homolog, Drosophila 0 rho-2 protein, Drosophila 147954-53-8 gil protein EC 2.7.1.112 Receptor, Epidermal Growth Factor EC 2.7.1.37 Mitogen-Activated Protein Kinases EC 2.7.1.37 Proto-Oncogene Proteins c-raf IM Animal Cell Differentiation Drosophila melanogaster embryology Eye Proteins metabolism Gene Expression Insect Proteins genetics Membrane Proteins genetics metabolism Mitogen-Activated Protein Kinases metabolism Nerve Tissue Proteins metabolism Proto-Oncogene Proteins c-raf metabolism Pupa growth & development Receptor, Epidermal Growth Factor metabolism Receptors, Invertebrate Peptide metabolism Signal Transduction Support, Non-U.S. Gov't Wing embryology FBrf0106053 99054981 9834198 1999 02 22 1999 02 22 2002 11 01

0950-1991 126 1 1999 Jan Direct activation of Sex-lethal transcription by the Drosophila runt protein. 191-200 Runt functions as a transcriptional regulator in multiple developmental pathways in Drosophila melanogaster. Recent evidence indicates that Runt represses the transcription of several downstream target genes in the segmentation pathway. Here we demonstrate that runt also functions to activate transcription. The initial expression of the female-specific sex-determining gene Sex-lethal in the blastoderm embryo requires runt activity. Consistent with a role as a direct activator, Runt shows sequence-specific binding to multiple sites in the Sex-lethal early promoter. Using an in vivo transient assay, we demonstrate that Runt's DNA-binding activity is essential for Sex-lethal activation in vivo. These experiments further reveal that increasing the dosage of runt alone is sufficient for triggering the transcriptional activation of Sex-lethal in males. In addition, a Runt fusion protein, containing a heterologous transcriptional activation domain activates Sex-lethal expression, indicating that this regulation is direct and not via repression of other repressors. Moreover, we demonstrate that a small segment of the Sex-lethal early promoter that contains Runt-binding sites mediates Runt-dependent transcriptional activation in vivo. Department of Biochemistry and Cell Biology and The Institute for Cell and Developmental Biology, State University of New York at Stony Brook, Stony Brook, New York 11794-5215, USA. Kramer S G SG Jinks T M TM Schedl P P Gergen J P JP eng GM53229 GM NIGMS Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 RNA-Binding Proteins 0 Runt protein 0 Sxl protein, Drosophila IM Animal Base Sequence Binding Sites DNA-Binding Proteins genetics metabolism Drosophila melanogaster embryology genetics Embryo, Nonmammalian Female Gene Dosage Gene Expression Regulation, Developmental Male Molecular Sequence Data Promoter Regions (Genetics) RNA-Binding Proteins genetics metabolism Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics) FBrf0076484 95047427 7958946 1994 12 01 1994 12 01 2003 07 04

0378-1119 148 2 1994 Oct 21 Cloning of a Drosophila melanogaster homologue of the mouse type-I bone morphogenetic proteins-2/-4 receptor: a potential decapentaplegic receptor. 203-9 The Drosophila melanogaster (Dm) decapentaplegic (dpp) gene product plays an essential role during several stages of Dm development. The DPP protein is a member of the transforming growth factor-beta (TGF-beta) superfamily and an orthologue of mammalian bone morphogenetic proteins (BMP-2 and -4). Recently, a cDNA clone encoding the mouse Ser/Thr kinase receptor specific for BMP-2/-4 (mTFR11) was isolated. Here, we describe the deduced primary structure, the cytogenetic position and expression pattern of the Dm homologue of mTFR11 (DTFR), a putative DPP receptor. The cytogenetic position of the Dm dtfr gene was mapped to 25D. DTFR has striking homology to mTFR11, especially in the cytoplasmic domain (approx. 63%), including a Ser + Gly-rich box that is characteristic of type-I receptors for the TGF-beta superfamily. Although the amino acid (aa) sequence of the extracellular domain is less conserved than that of the cytoplasmic domain, the extracellular domains of these two molecules were more homologous (approx. 27%) to each other than any other receptors for the TGF-beta superfamily. The spacing of Cys residues in the extracellular domain, which is considered crucial to ligand specificity, is highly conserved in these two receptors. During Dm embryonic development, its expression pattern changes in a dynamic fashion with high levels of expression in mesoderm and midgut, with some relation to dpp mutant phenotypes. Department of Molecular Neurobiology, University of Tokyo, Japan. Okano H H Yoshikawa S S Suzuki A A Ueno N N Kaizu M M Okabe M M Takahashi T T Matsumoto M M Sawamoto K K Mikoshiba K K eng GENBANK D30646 Z23143 Journal Article

NETHERLANDS Gene 7706761 0 Insect Hormones 0 RNA, Messenger 0 Receptors, Cell Surface 0 Receptors, Transforming Growth Factor beta 0 Transforming Growth Factor beta 0 bone morphogenetic protein receptors 0 dpp protein, Drosophila EC 1.5.1.3 Tetrahydrofolate Dehydrogenase EC 2.7.1.- DTFR protein, Drosophila IM dtfr Amino Acid Sequence Animal Base Sequence Cloning, Molecular Drosophila melanogaster genetics Insect Hormones metabolism Mice Molecular Sequence Data RNA, Messenger metabolism Receptors, Cell Surface chemistry genetics metabolism Receptors, Transforming Growth Factor beta chemistry genetics metabolism Sequence Homology, Amino Acid Support, Non-U.S. Gov't Tetrahydrofolate Dehydrogenase genetics Transforming Growth Factor beta metabolism FBrf0074249 94243034 8186464 1994 06 20 1994 06 20 2000 12 18

1059-1524 5 1 1994 Jan A family of dynein genes in Drosophila melanogaster. 45-55 We report the identification and initial characterization of seven Drosophila dynein heavy chain genes. Each gene is single copy and maps to a unique genomic location. Sequence analysis of partial clones reveals that each encodes a highly conserved portion of the putative dynein hydrolytic ATP-binding site in dyneins that includes a consensus phosphate-binding (P-loop) motif. One of the clones is derived from a Drosophila cytoplasmic dynein heavy chain gene, Dhc64C, that shows extensive amino acid identity to cytoplasmic dynein isoforms from other organisms. Two other Drosophila dynein clones are 85 and 90% identical at the amino acid level to the corresponding region of the beta heavy chain of sea urchin axonemal dynein. Probes for all seven of the dynein-related sequences hybridize to transcripts that are of the appropriate size, approximately 14 kilobases, to encode the characteristic high molecular weight dynein heavy chain polypeptides. The Dhc64C transcript is readily detected in RNA from ovaries, embryos, and testes. Transcripts from five of the six remaining genes are also detected in much lesser amounts in tissues other than testes. All but one of the dynein transcripts are expressed at comparable levels in testes suggesting their participation in flagellar axoneme assembly and motility. Department of Genetics and Cell Biology, University of Minnesota, St. Paul 55108. Rasmusson K K Serr M M Gepner J J Gibbons I I Hays T S TS eng GENBANK L23196 L23197 L23198 L23199 L23200 L23201 L25122 GM-30401 GM NIGMS GM-44757 GM NIGMS Journal Article

UNITED STATES Mol Biol Cell 9201390 56-65-5 Adenosine Triphosphate EC 3.6.1.33 Dynein ATPase IM Adenosine Triphosphate metabolism Amino Acid Sequence Animal Base Sequence Binding Sites Chromosome Mapping Comparative Study Consensus Sequence Drosophila melanogaster genetics Dynein ATPase genetics Genes, Structural, Insect Molecular Sequence Data Multigene Family Polymerase Chain Reaction Sea Urchins genetics Sequence Alignment Sequence Homology, Amino Acid Species Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0085406 96100388 8555105 1996 02 27 1996 02 27 2000 12 18

0925-4773 53 1 1995 Sep Trans-regulation of thoracic homeotic selector genes of the Antennapedia and bithorax complexes by the trithorax group genes: absent, small, and homeotic discs 1 and 2. 123-39 Genes of the trithorax group appear to be required for the maintenance of expression of the homeotic selector genes of the Antennapedia and bithorax complexes. According to genetic criteria, the Drosophila melanogaster genes absent, small, or homeotic discs 1 and 2 (ash1 and ash2) are members of the trithorax group. In this paper we examine the consequences of ash1 and ash2 mutations on the expression of homeotic selector genes in imaginal discs. The results of these experiments demonstrates that both ash1 and ash2 are trans-regulatory elements of homeotic selector gene regulation. Hypomorphic ash1 mutations cause variegated expression of Antennapedia, Sex combs reduced, Ultrabithorax, and engrailed. Complete loss of ash2 activity causes the loss of expression of Sex combs reduced in first leg imaginal discs, loss of expression of Ultrabithorax in third leg discs, and a late-patterned loss of expression of Ultrabithorax within haltere discs, yet has no effect on engrailed or Antennapedia expression. These results suggest that the range and action of trithorax group genes is varied and complex and argue against any model in which all of the products of the trithorax group act together in a single mechanism or complex. Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. LaJeunesse D D Shearn A A eng AG 01822 AG NIA Journal Article

IRELAND Mech Dev 9101218 EC 3.2.1.23 beta-Galactosidase IM Animal Drosophila melanogaster genetics Gene Expression Regulation, Developmental physiology Genes, Homeobox Genes, Insect Genes, Regulator Immunohistochemistry Larva genetics Mutation Support, U.S. Gov't, P.H.S. Thorax beta-Galactosidase analysis FBrf0108054 99196982 10095103 1999 05 17 1999 05 17 2000 12 18

0378-1119 229 1-2 1999 Mar 18 GEM, a cluster of repetitive sequences in the Drosophila subobscura genome. 47-57 GEM is a new family of repetitive sequences detected in the D. subobscura genome. Two of the four described GEM elements encompass a heterogeneous central module, with no detectable ORF, flanked by two long inverted repeats. These elements are composed of a set of repetitive modules, which are inverted repeat (IR), direct repeat (DR), palindromic sequence (PS), long sequence (LS) and short sequence (SS). These five modules can be found either clustered or dispersed as single modules in the D. subobscura genome, in euchromatic and heterochromatic regions. In addition to the 3' region of Adh retrosequences, single IR and LS blocks were found associated with the promoter region of different genes, in particular, LS-like blocks have also been found associated with functional genes in D. melanogaster and D. virilis. Conversely, the DR block is highly similar to satellite DNAs from some other species of the obscura group. In addition, GEM elements share some structural features with IS elements described in different Drosophila species. It is likely that both GEM and IS sequences would be vestiges of an ancestral transposable element. Departamento de Genética, Facultad de Ciencias Biológicas, Dr. Moliner 50, Burjassot 46100, Valencia, Spain. Vivas M V MV García-Planells J J Ruiz C C Marfany G G Paricio N N Gonzàlez-Duarte R R de Frutos R R eng GENBANK AJ131628 AJ131629 Journal Article

NETHERLANDS Gene 7706761 0 DNA Transposable Elements EC 1.1.1.1 Alcohol Dehydrogenase IM Alcohol Dehydrogenase genetics Animal Base Sequence Cloning, Molecular DNA Transposable Elements genetics Drosophila genetics Evolution, Molecular Genes, Insect Genome Molecular Sequence Data Repetitive Sequences, Nucleic Acid genetics Sequence Alignment Support, Non-U.S. Gov't TATA Box genetics FBrf0054740 91141550 1996129 1991 03 25 1991 03 25 2000 12 18

0027-5107 252 1 1991 Feb Inhalation exposure in Drosophila mutagenesis assays: experiments with aliphatic halogenated hydrocarbons, with emphasis on the genetic activity profile of 1,2-dichloroethane. 17-33 A series of mutation experiments was carried out with Drosophila melanogaster using inhalation exposure. 1,2-Dichloroethane (DCE) and 1,2-dibromoethane (DBE) were active in the sex-linked recessive lethal assay (SLRLT), whereas dichloromethane, dibromomethane, 1,2-dichloropropane and 1,3-dichloropropane were not. Compared to DBE, DCE is a less potent mutagen in the SLRL system. For both compounds, there is no evidence of a clear-cut dose-rate effect. DCE and dichloromethane were also investigated in the somatic mutation and recombination test (SMART), with results similar to those from the SLRLT. For DCE the genetic activity profile was further analyzed by carrying out a sex-chromosome loss assay and a complementation analysis of a series of induced recessive lethal mutations. A review of the use of inhalation in mutagenicity assays with Drosophila shows that this route of exposure is an effective one. Especially with chronic exposure times, rather low exposure concentrations can be detected. With compounds of intermediate volatility inhalation is not superior to other modes of administration; nor is it likely to be sensitive enough for in situ monitoring. National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands. Kramers P G PG Mout H C HC Bissumbhar B B Mulder C R CR eng Journal Article

NETHERLANDS Mutat Res 0400763 0 Ethylene Dichlorides 0 Hydrocarbons, Brominated 0 Hydrocarbons, Halogenated 106-93-4 Ethylene Dibromide 107-06-2 ethylene dichloride 142-28-9 1,3-dichloropropane 70-18-8 Glutathione 74-95-3 methylene bromide 74-98-6 Propane 75-09-2 Methylene Chloride 78-87-5 propylene dichloride IM Administration, Inhalation Animal Chromosome Mapping Dose-Response Relationship, Drug Drosophila genetics Ethylene Dibromide toxicity Ethylene Dichlorides toxicity Gene Frequency Genes, Lethal Glutathione metabolism Hydrocarbons, Brominated toxicity Hydrocarbons, Halogenated toxicity Male Methylene Chloride toxicity Mutagenesis drug effects Mutation Propane analogs & derivatives toxicity Recombination, Genetic drug effects Ring Chromosomes FBrf0044226 87053871 3023068 1986 12 19 1986 12 19 2000 12 18

0261-4189 5 9 1986 Sep The anterobithorax and bithorax mutations of the bithorax complex. 2293-303 The anterobithorax (abx) and bithorax (bx) genes together direct the development of the posterior second and anterior third thoracic segments of the fruit fly. We have characterized the phenotypes and DNA lesions of 19 abx and bx alleles. abx and bx mutations differ both in the nature and location of their DNA lesions, forming two clusters within a relatively small region of the Ultrabithorax transcription unit. Correlation between phenotype and DNA lesion suggests the presence of two or more genetic elements in this region distinct from the Ultrabithorax transcript. Mutant transformations do not strictly obey segmental or parasegmental boundaries. Most of the bx mutations result from insertions of the mobile element gypsy. The strength of these alleles varies in a regular way dependent on the position and orientation of the gypsy element. We propose models for gypsy element action and bithorax complex expression in the light of these results. Peifer M M Bender W W eng Journal Article

ENGLAND EMBO J 8208664 0 DNA Transposable Elements 0 DNA, Recombinant IM Animal Chromosome Deletion Crosses, Genetic DNA Transposable Elements DNA, Recombinant metabolism Drosophila melanogaster anatomy & histology genetics Genes Mutation Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Thorax anatomy & histology FBrf0145167 21824255 11835058 2002 02 08 2002 08 08

1465-7392 4 2 2002 Feb Establishing cell polarity in development. E39-44 Polarity is a common feature of many different cell types, including the Caenorhabditis elegans zygote, the Drosophila oocyte and mammalian epithelial cells. The initial establishment of cell polarity depends on asymmetric cues that lead to reorganization of the cytoskeleton and polarized localization of several cortical proteins that act downstream of the polarization cues. The past year revealed that homologs of the C. elegans par (partitioning defective) genes are also essential for establishing polarity in Drosophila and vertebrate cells. There is growing evidence that the proteins encoded by these genes interact with key regulators of both the actin and the microtubule cytoskeletons. Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. wodarz@uni-duesseldorf.de Wodarz Andreas A eng Journal Article Review Review, Tutorial

England Nat Cell Biol 100890575 0 Cytoskeletal Proteins IM Animal Caenorhabditis elegans cytology physiology Cell Polarity Cytoskeletal Proteins metabolism Drosophila melanogaster physiology Epithelial Cells cytology metabolism Human Models, Biological Oogenesis Support, Non-U.S. Gov't Zygote metabolism 72 FBrf0090690 97108751 8951072 1997 01 23 1997 01 23 2000 12 18

0950-1991 122 11 1996 Nov hedgehog signaling independent of engrailed and wingless required for post-S1 neuroblast formation in Drosophila CNS. 3567-75 The hedgehog gene product, secreted from engrailed-expressing neuroectoderm, is required for the formation of post-S1 neuroblasts in rows 2, 5 and 6. The hedgehog protein functions not only as a paracrine but also as an autocrine factor and its transient action on the neuroectoderm 1-2 hours (at 18 degrees C) prior to neuroblast delamination is necessary and sufficient to form normal neuroblasts. In contrast to epidermal development, hedgehog expression required for neuroblast formation is regulated by neither engrailed nor wingless. hedgehog and wingless bestow composite positional cues on the neuroectodermal regions for S2-S4 neuroblasts at virtually the same time and, consequently, post-S1 neuroblasts in different rows can acquire different positional values along the anterior-posterior axis. The average number of proneural cells for each of three eagle-positive S4-S5 neuroblasts was found to be 5-9, the same for S1 NBs. As with wingless (Chu-LaGraff et al., Neuron 15, 1041-1051, 1995), huckebein expression in putative proneural regions for certain post-S1 neuroblasts is under the control of hedgehog. hedgehog and wingless are involved in separate, parallel pathways and loss of either is compensated for by the other in NB 7-3 formation. NBs 6-4 and 7-3, arising from the engrailed domain, were also found to be specified by the differential expression of two homeobox genes, gooseberry-distal and engrailed. Department of Biophysics and Biochemistry, University of Tokyo, Bunkyo-ku, Japan. Matsuzaki M M Saigo K K eng Journal Article

ENGLAND Development 8701744 0 Homeodomain Proteins 0 Insect Hormones 0 Proteins 0 Proto-Oncogene Proteins 0 Transcription Factors 0 engrail protein, Drosophila 117758-26-6 wingless protein, Drosophila 149291-21-4 hedgehog protein, Drosophila IM Animal Body Patterning Central Nervous System embryology Drosophila melanogaster embryology Ectoderm cytology Genes, Homeobox Homeodomain Proteins physiology Insect Hormones physiology Neurons cytology Proteins physiology Proto-Oncogene Proteins physiology Support, Non-U.S. Gov't Transcription Factors physiology FBrf0047011 88121735 3123894 1988 02 26 1988 02 26 2000 12 18

0026-8925 210 3 1987 Dec Studies on transvection at the bithorax complex in Drosophila melanogaster. 557-63 We have studied the influence of some mutations in the bithorax complex on the observed synapsis dependent phenotype of the genotypes Cbx1Ubx1/+ and bx3 4e/Ubx1. The effect of these mutations is similar to that introduced by disruption of pairing or by the za mutation. Among the bx mutations, we find that bx8 behaves differently from most other bx mutations in its influence on the synapsis dependent phenotype. This observation induced us to map the position of bx8 with respect to other bx mutations; we find that it maps between bx3 4e and bx3. We show how some of the observations reported here can be fitted into a model of activation of the bithorax complex proposed by one of us. Molecular Biology Unit, Tata Institute of Fundamental Research, Bombay, India. Babu P P Selvakumar K S KS Bhosekar S S eng Journal Article

GERMANY, WEST Mol Gen Genet 0125036 IM Animal Chromosome Mapping Drosophila melanogaster embryology genetics Gene Expression Regulation Genetic Complementation Test Meiosis Morphogenesis Mutation Phenotype Thorax FBrf0079925 95157518 7854314 1995 03 16 1995 03 16 2000 12 18

0026-8925 246 3 1995 Feb 6 Genetic interactions and dosage effects of Polycomb group genes of Drosophila. 291-300 The Polycomb (Pc) group of genes are required for maintenance of cell determination in Drosophila melanogaster. At least 11 Pc group genes have been described and there may be up to 40; all are required for normal regulation of homeotic genes, but as a group, their phenotypes are rather diverse. It has been suggested that the products of Pc group genes might be members of a heteromeric complex that acts to regulate the chromatin structure of target loci. We examined the phenotypes of adult flies heterozygous for every pairwise combination of Pc group genes in an attempt to subdivide the Pc group functionally. The results support the idea that Additional sex combs (Asx), Pc, Polycomblike (Pcl), Posterior sex combs (Psc), Sex combs on midleg (Scm), and Sex combs extra (Sce) have similar functions in some imaginal tissues. We show genetic interactions among extra sex combs (esc) and Asx, Enhancer of Pc, Pcl, Enhancer of zeste E(z), and super sex combs and reassess the idea that most Pc group genes function independently of esc. Most duplications of Pc group genes neither exhibit anterior transformations nor suppress the extra sex comb phenotype of Pc group mutations, suggesting that not all Pc group genes behave as predicted by the mass-action model. Surprisingly, duplications of E(z) enhance homeotic phenotypes of esc mutants. Flies with increasing doses of esc+ exhibit anterior transformations, but these are not enhanced by mutations in trithorax group genes. The results are discussed with respect to current models of Pc group function. Department of Zoology, University of British Columbia, Vancouver, Canada. Campbell R B RB Sinclair D A DA Couling M M Brock H W HW eng Journal Article

GERMANY Mol Gen Genet 0125036 0 Proteins 134549-01-2 Polycomb protein, insect IM Alleles Animal Crosses, Genetic Drosophila melanogaster embryology genetics growth & development Female Gene Dosage Genes, Insect physiology Genes, Lethal Genes, Regulator physiology Male Mutation genetics Phenotype Proteins genetics Support, Non-U.S. Gov't Suppression, Genetic FBrf0058578 93216093 8462854 1993 05 06 1993 05 06 2000 12 18

0016-6731 133 4 1993 Apr Complex function and expression of Delta during Drosophila oogenesis. 967-78 Delta (Dl) encodes a cell surface protein that mediates cell-cell interactions central to the specification of a variety of cell fates during embryonic and postembryonic development of Drosophila melanogaster. We find that the Delta protein is expressed intermittently in follicle cells and in germ-line cells during stages 1-10 of oogenesis. Furthermore, Delta expression during oogenesis can be correlated with a number of morphogenetic defects associated with sterility observed in Dl mutant females, including failure of stalk formation within the germarium and subsequent fusion of egg chambers, necrosis in germ-line cells, and multiphasic embryonic arrest of fertilized eggs. We have also identified a Dl mutation that leads to context-dependent defects in Dl function during oogenesis. Direct comparison of Delta protein expression with that of the Notch protein in the ovary reveals substantial, but incomplete, coincidence of expression patterns in space and time. We discuss possible roles for the Delta protein in cell-cell interactions required for cell fate specification processes during oogenesis in light of available developmental and histochemical data. Department of Biology, Indiana University, Bloomington 47405. Bender L B LB Kooh P J PJ Muskavitch M A MA eng GM33291 GM NIGMS Journal Article

UNITED STATES Genetics 0374636 0 Insect Hormones 0 Membrane Proteins 0 delta protein 0 notch protein IM Dl Alleles Animal Drosophila melanogaster embryology genetics physiology Female Gene Expression Insect Hormones genetics physiology Larva Male Membrane Proteins genetics physiology Mutation Oogenesis genetics physiology Ovary cytology physiology Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. FBrf0158945 22557627 12670867 2003 04 02 2003 05 07

0890-9369 17 7 2003 Apr 1 In vivo analysis of a developmental circuit for direct transcriptional activation and repression in the same cell by a Runx protein. 838-43 Runx proteins have been implicated in acute myeloid leukemia, cleidocranial dysplasia, and stomach cancer. These proteins control key developmental processes in which they function as both transcriptional activators and repressors. How these opposing regulatory modes can be accomplished in the in vivo context of a cell has not been clear. In this study we use the developing cone cell in the Drosophila visual system to elucidate the mechanism of positive and negative regulation by the Runx protein Lozenge (Lz). We describe a regulatory circuit in which Lz causes transcriptional activation of the homeodomain protein Cut, which can then stabilize a Lz repressor complex in the same cell. Whether a gene is activated or repressed is determined by whether the Lz activator or the repressor complex binds to its upstream sequence. This study provides a mechanistic basis for the dual function of Runx proteins that is likely to be conserved in mammalian systems. Department of Biological Chemistry and Department of Molecular, Cell, and Developmental Biology, Molecular Biology Institute, University of California-Los Angeles, Los Angeles, CA 90095, USA. Canon Jude J Banerjee Utpal U eng EY 08152 EY NEI GM 07185 GM NIGMS Journal Article

United States Genes Dev 8711660 0 Cut protein 0 DNA Probes 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Insect Hormones 0 Nerve Tissue Proteins 0 Nuclear Proteins 0 Repressor Proteins 0 Transcription Factors 0 lozenge protein, Drosophila IM Animal Animals, Genetically Modified Base Sequence Binding Sites Cell Line DNA Probes DNA-Binding Proteins genetics Drosophila Proteins genetics Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Insect Hormones genetics Nerve Tissue Proteins genetics Nuclear Proteins genetics Repressor Proteins metabolism Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics) physiology Transcription Factors genetics Transfection FBrf0058121 94357076 8076519 1994 10 03 1994 10 03 2002 11 01

0950-1991 118 3 1993 Jul Sex determination in the germ line of Drosophila melanogaster: activation of the gene Sex-lethal. 813-6 The germ line exhibits sexual dimorphism as do the somatic tissues. Cells with the 2X;2A chromosome constitution will follow the oogenic pathway and X;2A cells will develop into sperm. In both somatic and germ-line tissues, the sexual pathway chosen by the cells depends on the gene Sex-lethal (Sxl), whose function is continuously needed for female development. In the soma, the sex of the cells is autonomously determined by the X:A signal while, in the germ line, the sex is determined by cell autonomous (the X:A signal) and somatic inductive signals. Three X-linked genes have been identified, scute (sc), sisterless-a (sis-a) and runt (run), that determine the initial functional state of Sxl in the soma. Using pole cell transplantation, we have tested whether these genes are also needed to activate Sxl in the germ line. We found that germ cells simultaneously heterozygous for sc, sis-a, run and a deficiency for Sxl transplanted into wild-type female hosts develop into functional oocytes. We conclude that the genes sc, sis-a and run needed to activate Sxl in the soma seem not to be required to activate this gene in the germ line; therefore, the X:A signal would be made up by different genes in somatic and germ-line tissues. The Sxlf7M1/Sxlfc females do not have developed ovaries. We have shown that germ cells of this genotype transplanted into wild-type female hosts produce functional oocytes. We conclude that the somatic component of the gonads in Sxlf7M1/Sxlfc females is affected, and consequently germ cells do not develop.(ABSTRACT TRUNCATED AT 250 WORDS) Centro de Investigaciones Biológicas, Madrid, Spain. Granadino B B Santamaria P P Sánchez L L eng Journal Article

ENGLAND Development 8701744 0 DNA-Binding Proteins 0 Insect Hormones 0 Runt protein 0 Sxl protein, Drosophila 0 Transcription Factors 0 scute protein, Drosophila 0 sisterless-a protein IM Sxl Sxl<up>7M1</up> Sxl<up>fc</up> dpn liz ovo ovov run sc sis-a snf Animal DNA-Binding Proteins genetics physiology Drosophila melanogaster embryology genetics Female Gene Expression Regulation Genes, Structural, Insect Germ Cells transplantation Insect Hormones biosynthesis genetics Male Mutation Sex Determination (Analysis) Support, Non-U.S. Gov't Transcription Factors genetics physiology X Chromosome FBrf0035968 82116475 6799259 1982 04 12 1982 04 12 2000 12 18

0009-5915 84 2 1981 Cytogenetic and genetic mapping of a salivary gland secretion protein in Drosophila melanogaster. 173-85 The larval salivary gland secretion of Drosophila melanogaster is separated, by acid-urea polyacrylamide electrophoresis, into several different protein components. The genes specifying three of these had hitherto been located both genetically and cytogenetically, and shown to map close to sites that form prominent puffs in larval salivary gland chromosomes. A fourth component of the secretion (SGS-6), present in some, but not all, stocks of D. melanogaster, is shown to be under the control of a gene that maps to 3-42.0 and to bands 71 C1,2-71 F3,5. In those stocks that possess SGS-6 a puff is active in 71 C3-4 in Puff Stage 1, but not in older larvae. We conclude that this puff is the manifestation of a transcriptionally active Sgs-6 gene. Velissariou V V Ashburner M M eng Journal Article

GERMANY, WEST Chromosoma 2985138R 0 Salivary Proteins IM Animal Chromosome Mapping Chromosomes ultrastructure Drosophila melanogaster genetics Electrophoresis, Polyacrylamide Gel Genes, Structural Larva metabolism Salivary Proteins genetics Support, Non-U.S. Gov't FBrf0155997 22399855 12510193 2003 01 03 2003 02 21 2003 06 16

1465-7392 5 1 2003 Jan Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. 46-52 Several protein complexes that are involved in epithelial apicobasal polarity have been identified. However, the mechanism by which these complexes interact to form an integrated polarized cell morphology remains unclear. Crumbs (Crb) and Lethal giant larvae (Lgl) are components of distinct complexes that regulate epithelial polarization in Drosophila melanogaster, but may not interact directly as they localize to the apical and basolateral membrane, respectively. Nevertheless, a genetic screen identifies marked functional interactions between crb and lgl. These interactions extend to other genes within the crb (stardust, sdt) and lgl (discs large, dlg; scribble, scrib) pathways. Our findings suggest that the crb and lgl pathways function competitively to define apical and basolateral surfaces. They also suggest that in the absence of lgl pathway activity, the crb pathway is not required to maintain epithelial polarity. Moreover, we show that crb and lgl cooperate in zonula adherens formation early in development. At later stages, epithelial cells in these mutants acquire normal polarity, indicating the presence of compensatory mechanisms. We find that bazooka (baz) functions redundantly with crb/sdt to support apical polarity at mid- to late-embryogenesis. Despite regaining cell polarity, however, epithelial cells in crb and lgl pathway mutants fail to re-establish normal overall tissue architecture, indicating that the timely acquisition of polarized cell structure is essential for normal tissue organization. Department of Zoology, University of Toronto, Toronto, Ontario M5S 3G5, Canada. Tanentzapf Guy G Tepass Ulrich U eng Journal Article

England Nat Cell Biol 100890575 0 Drosophila Proteins 0 Membrane Proteins 0 crb protein, Drosophila 0 lethal (2) giant larvae protein, Drosophila IM Nat Cell Biol. 2003 Jan;5(1):12-4 12511884 Animal Cell Differentiation Cell Polarity physiology Drosophila Proteins physiology Drosophila melanogaster embryology growth & development physiology Embryo, Nonmammalian cytology physiology Epithelial Cells cytology physiology ultrastructure Larva Membrane Proteins physiology Microscopy, Electron Support, Non-U.S. Gov't FBrf0056178 93093478 1334025 1993 01 14 1993 01 14 2003 06 16

0016-6707 87 1 1992 Super-unstable mutations associated with P-M hybrid dysgenesis in Drosophila melanogaster. 17-29 Super-unstable mutations occasionally appear either in natural populations of Drosophila melanogaster or in P-M hybrid dysgenesis. We found that they may be reproducibly obtained with a high frequency from crosses between males from the pi 2 strain and females from the waG* strain or its derivatives. Super-unstable mutations in the ocelliless, singed, white, yellow and other loci have been obtained. Each super-unstable mutation gives rise to a large family of new super-unstable mutations with a wide range of phenotypic expression. Mutations with the same phenotype often differ in the specificity of their potential for further mutation. As a rule, a super-unstable mutation is associated with a specific reversible mutation and paired alleles are formed in this way. Other mutations are usually irreversible, but new mutations of these may also form paired alleles. Active transposase encoded by transposable P elements is necessary to maintain super-instability. Finally, some preliminary molecular data are discussed which suggest that this type of super-instability is a result of interaction between P elements and a novel mobile element, designated as X. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow. Georgiev P P Yelagin V V eng Journal Article

NETHERLANDS Genetica 0370740 0 DNA Transposable Elements 0 Insect Hormones 0 white protein, Drosophila 0 yellow protein, Drosophila EC 2.7.7 Nucleotidyltransferases EC 2.7.7.- Transposase IM Animal DNA Transposable Elements Drosophila melanogaster genetics Female Hybridization, Genetic genetics Insect Hormones genetics Male Mutation Nucleotidyltransferases metabolism Transposase FBrf0042035 86079532 3935322 1986 02 12 1986 02 12 2000 12 18

0092-8674 43 2 Pt 1 1985 Dec Regulation of the Ultrabithorax gene of Drosophila by other bithorax complex genes. 507-19 The bithorax complex of Drosophila is composed of three major units of gene function, Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B), each having a precise realm of action within the thorax and abdomen. Recent molecular studies have established that the transcripts and protein products of the Ubx gene are expressed principally in a restricted portion of the body, beginning in the second thoracic segment and ending in the eighth abdominal segment (i.e., in parasegments 5-13). However, within this region, both show complex, heterogeneous patterns of expression. Using mutations in the abd-A, Abd-B, and esc (extra sex combs) genes we show that these distinct patterns result in large part from regulation of Ubx gene expression by the abd-A and Abd-B gene functions. Struhl G G White R A RA eng 5 PO1 GM29301 GM NIGMS Journal Article

UNITED STATES Cell 0413066 IM Animal Drosophila melanogaster anatomy & histology genetics growth & development Embryo, Nonmammalian anatomy & histology Gene Expression Regulation Larva anatomy & histology Morphogenesis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transcription, Genetic FBrf0138518 21417728 11504926 2001 08 29 2001 10 04 2003 01 03

0027-8424 98 18 2001 Aug 28 Hemocytes are essential for wing maturation in Drosophila melanogaster. 10190-5 Newly eclosed flies have wings that are highly folded and compact. Within an hour, each wing has expanded, the dorsal and ventral cuticular surfaces bonding to one another to form the mature wing. To initiate a dissection of this process, we present studies of two mutant phenotypes. First, the batone mutant blocks wing expansion, a behavior that is shown to have a mutant focus anterior to the wing in the embryonic fate map. Second, ectopic expression of protein kinase A catalytic subunit (PKAc) using certain GAL4 enhancer detector strains mimics the batone wing phenotype and also induces melanotic "tumors." Surprisingly, these GAL4 strains express GAL4 in cells, which seem to be hemocytes, found between the dorsal and ventral surfaces of newly opened wings. Ectopic expression of Ricin A in these cells reduces their number and prevents bonding of the wing surfaces without preventing wing expansion. We propose that hemocytes are present in the wing to phagocytose apoptotic epithelial cells and to synthesize an extracellular matrix that bonds the two wing surfaces together. Hemocytes are known to form melanotic tumors either as part of an innate immune response or under other abnormal conditions, including evidently ectopic PKAc expression. Ectopic expression of PKAc in the presence of the batone mutant causes dominant lethality, suggesting a functional relationship. We propose that batone is required for the release of a hormone necessary for wing expansion and tissue remodeling by hemocytes in the wing. Molecular and Cellular Biology, University of California, 1 Shields Avenue, Davis, CA 95616, USA. jakiger@ucdavis.edu Kiger J A JA Jr Natzle J E JE Green M M MM eng Journal Article 2001 08 14

United States Proc Natl Acad Sci U S A 7505876 9009-86-3 Ricin EC 2.7.1.37 Cyclic AMP-Dependent Protein Kinases IM Animal Animals, Genetically Modified Cyclic AMP-Dependent Protein Kinases genetics Drosophila melanogaster cytology genetics growth & development Gene Expression Genes, Dominant Genes, Insect Genes, Lethal Hemocytes cytology Mutation Phenotype Ricin genetics Support, Non-U.S. Gov't Wing growth & development FBrf0155705 22354100 12466192 2002 12 05 2003 03 10

0950-1991 130 2 2003 Jan Activation of the knirps locus links patterning to morphogenesis of the second wing vein in Drosophila. 235-48 The adjacent knirps (kni) and knirps-related (knrl) genes encode functionally related zinc finger transcription factors that collaborate to initiate development of the second longitudinal wing vein (L2). kni and knrl are expressed in the third instar larval wing disc in a narrow stripe of cells just anterior to the broad central zone of cells expressing high levels of the related spalt genes. Here, we identify a 1.4 kb cis-acting enhancer element from the kni locus that faithfully directs gene expression in the L2 primordium. We find that three independent ri alleles have alterations mapping within the L2-enhancer element and show that two of these observed lesions eliminate the ability of the enhancer element to direct gene expression in the L2 primordium. The L2 enhancer can be subdivided into distinct activation and repression domains. The activation domain mediates the combined action of the general wing activator Scalloped and a putative locally provided factor, the activity of which is abrogated by a single nucleotide alteration in the ri(53j) mutant. We also find that misexpression of genes in L2 that are normally expressed in veins other than L2 results in abnormal L2 development. These experiments provide a mechanistic basis for understanding how kni and knrl link AP patterning to morphogenesis of the L2 vein by orchestrating the expression of a selective subset of vein-promoting genes in the L2 primordium. Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349, USA. Lunde Karen K Trimble Jennifer L JL Guichard Annabel A Guss Kirsten A KA Nauber Ulrich U Bier Ethan E eng 1F32HD08326 HD NICHD R01 GM60585 GM NIGMS Journal Article

England Development 8701744 0 DNA-Binding Proteins 0 Drosophila Proteins 0 Insect Hormones 0 KNI protein 0 Repressor Proteins 0 Transcription Factors 0 scalloped protein IM Alleles Animal Base Sequence Body Patterning DNA-Binding Proteins genetics metabolism Drosophila Proteins genetics metabolism Drosophila melanogaster genetics growth & development Enhancer Elements (Genetics) Gene Expression Regulation, Developmental Genes, Insect In Situ Hybridization Insect Hormones metabolism Molecular Sequence Data Morphogenesis Protein Binding Repressor Proteins genetics metabolism Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S. Transcription Factors metabolism Transgenes Wing anatomy & histology growth & development FBrf0151929 22283630 12397101 2002 10 24 2002 12 03

0950-1991 129 21 2002 Nov Transcription activates repressed domains in the Drosophila bithorax complex. 4923-30 A series of mutations have been recovered in the bithorax complex of D. melanogaster that transform the first segment of the abdomen into a copy of the second or third abdominal segment. These dominant Ultraabdominal alleles are all associated with P element insertions which are transcribed in the first abdominal segment. The transcripts proceed past the end of the P element for up to 50 kb, extending through the regulatory regions for the second and third abdominal segments. Blocking transcription from the P element promoter reverts the mutant phenotype. Previously identified Ultraabdominal alleles, not associated with P elements, also show abnormal transcription of the same region. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Bender Welcome W Fitzgerald Daniel P DP eng Journal Article

England Development 8701744 63231-63-0 RNA IM Alleles Animal Body Patterning genetics Drosophila melanogaster genetics growth & development Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Genes, Regulator Multigene Family Mutation Phenotype Promoter Regions (Genetics) RNA genetics Transcription, Genetic FBrf0055061 92073903 1962194 1992 01 08 1992 01 08 2000 12 18

0036-8075 254 5036 1991 Nov 29 A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. 1359-61 Three cytoplasmic proteins, called catenins, bind to the cytoplasmic tail of the epithelial cell-cell adhesion molecule E-cadherin. The complementary DNA sequence was determined for the 92-kilodalton beta catenin of Xenopus laevis. The sequence is homologous to mammalian plakoglobin, a protein of desmosomal and zonula adherens cell junctions, and to the plakoglobin homolog in Drosophila melanogaster, the product of the segment polarity gene armadillo. A monoclonal antibody to bovine plakoglobin recognizes the analogous beta catenin in the Madin-Darby canine kidney (MDCK) cell line. Armadillo plakoglobin may link E-cadherin to the underlying actin cytoskeleton at cell-cell junctions; the E-cadherin-catenin protein complex may also participate in the transmission of developmental information. Department of Pharmacology, University of California, San Francisco 94143. McCrea P D PD Turck C W CW Gumbiner B B eng GENBANK M63875 M65143 M74517 M76239 M76240 M76241 M76242 M76243 M76244 M77013 5-F32-GM-13060 GM NIGMS GM37432 GM NIGMS Journal Article

UNITED STATES Science 0404511 0 Cadherins 0 Cytoskeletal Proteins 0 desmoplakin 146409-33-8 beta catenin 9007-49-2 DNA IM Amino Acid Sequence Animal Cadherins genetics Cell Line Comparative Study Cytoskeletal Proteins genetics DNA genetics Drosophila melanogaster genetics Molecular Sequence Data Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Xenopus laevis FBrf0098246 97454252 9310327 1997 10 28 1997 10 28 2003 06 16

0950-1991 124 17 1997 Sep A genetic screen for modifiers of Deformed homeotic function identifies novel genes required for head development. 3321-31 Only a few genes have been identified that participate in the developmental pathways which modulate homeotic (HOX) protein specificity or mediate HOX morphogenetic function. To identify more HOX pathway genes, we screened for mutations on loci on the Drosophila second chromosome that interact with the homeotic gene Deformed (Dfd). Genetic and molecular tests on the eight genes isolated in the screen place them in three general categories. Two genes appear to encode trithorax group functions, i.e. they are general activators of Hox gene expression or function. Four genes encode abundant, widely expressed proteins that may be required to mediate Dfd morphogenetic functions in certain tissues, including two genes for collagen IV protein variants. Finally, two of the genes are required for the development of a subset of embryonic Dfd-dependent structures, while leaving many other segmental structures intact. We cloned and characterized one of these two, which we have named apontic (apt). apt is required for the elaboration of dorsal and ventral head structures. It encodes a 484-amino-acid protein with no significant similarity to known protein sequences. The apt transcript pattern is normal in Dfd and Scr mutants, and the Dfd and Scr transcript patterns are normal in apt mutants. We propose that apt acts in parallel to, or as a cofactor with, HOX proteins to regulate homeotic targets in the ventral gnathal region. Department of Biology, Yale University, New Haven, CT 06520-8114, USA. Gellon G G Harding K W KW McGinnis N N Martin M M MM McGinnis W W eng GENBANK AF009676 HD30368 HD NICHD Journal Article

ENGLAND Development 8701744 0 Dfd protein 0 Homeodomain Proteins 0 Insect Proteins 0 apontic protein, Drosophila 134549-01-2 Polycomb protein, insect IM Amino Acid Sequence Animal Drosophila melanogaster embryology genetics metabolism Female Gene Expression Regulation, Developmental Genes, Homeobox Genes, Insect Genetic Complementation Test Head embryology Homeodomain Proteins genetics metabolism In Situ Hybridization Insect Proteins genetics metabolism Male Molecular Sequence Data Mutation Phenotype Support, U.S. Gov't, P.H.S. FBrf0125149 20123178 10659782 2000 04 14 2000 04 14 2003 06 16

0831-2796 42 6 1999 Dec Genetic organization of the ci-M-pan region on chromosome IV in Drosophila melanogaster. 1144-9 The genes cubitus interruptus (ci), ribosomal protein S3A (RpS3A), and pangolin (pan) are localized within 73 kb in the cytological region 101F-102A on chromosome IV in Drosophila melanogaster. A region of 13 kb harbours the regulatory regions of both ci and pan, transcribed in opposite directions, and a 1.1-kb gene encoding RpS3A. This dense clustering gives rise to very complicated complementation patterns between different alleles in these loci. We investigated this region genetically and molecularly by use of an enhancer trap line (IA5), where the P-element was found to be inserted into the first intron of pan. Screens for imprecise excisions of the P-element were performed, and complementations between new and old established mutant lines were investigated. We found that when mutated or deleted the RpS3A gene gives rise to a Minute phenotype, and we conclude that M(4)101 encodes the ribosomal protein S3A. Department of Genetics, Umeå University, Sweden. Kronhamn J J Rasmuson-Lestander A A eng Journal Article

CANADA Genome 8704544 0 DNA Transposable Elements 0 DNA-Binding Proteins 0 Insect Proteins 0 Ribosomal Proteins 0 Transcription Factors 0 cubitus interruptus protein 0 ribosomal protein S3a, insect EC 3.2.1.23 beta-Galactosidase IM Animal Blotting, Northern DNA Transposable Elements DNA-Binding Proteins genetics Drosophila melanogaster embryology genetics Female Genes, Insect Genetic Complementation Test Insect Proteins genetics Male Ribosomal Proteins genetics Support, Non-U.S. Gov't Transcription Factors genetics beta-Galactosidase genetics