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Second-site modifiers of the split mutation of Notch define genes involved in neurogenesis in Drosophila melanogaster

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Summary

We have searched for dominant modifiers, i.e., enhancers and suppressors, of the compound eye phenotype of split, a recessive viable allele of Notch. Among the spl modifiers found, we have detected mutations in loci whose functions were previously known to cooperate with Notch in embryonic neurogenesis, such as daughterless, master mind, Delta and Hairless. In addition, other spl modifier mutations have been found in loci that were not previously known to interact with Notch, such as scabrous, glass, roughened eye, and several other genes that have not yet been assigned to known loci. The phenotypes associated with mutations in some of these latter loci suggest the participation of the corresponding genes in embryonic neurogenesis. We show that in some cases the observed interactions are due to genetic haplo-insufficent expression of the genes, whereas allele-specific interactions with spl are observed in master mind and Delta alleles. From this observation, we propose a direct functional association between the proteins encoded by Notch, Delta and master mind.

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References

  • Agnel M, Kerridge S, Vola C, Griffin-Shea R (1989) Two transcripts from the rotund region of Drosophila show similar positional specificities in imaginal disc tissues. Genes Dev 3:85–95

    Google Scholar 

  • Bier E, Ackerman L, Barbel S, Jan L, Jan YN (1988) Identification and characterization of a neuron-specific nuclear antigen in Drosophila. Science 240:913–916

    Google Scholar 

  • Bodmer R, Jan YN (1987) Morphological differentiation of the embryonic peripheral neurons in Drosophila. Wilhelm Roux's Arch 196:69–77

    Google Scholar 

  • Botas J, Moscoso del Prado J, Garcia-Bellido A (1982) Gene-dose titration analysis in the search of trans-regulatory genes in Drosophila. EMBO J 1:307–310

    Google Scholar 

  • Botstein D, Maurer R (1982) Genetic approaches to the analysis of microbial development. Annu Rev Gen 16:61–83

    Google Scholar 

  • Brand M, Campos-Ortega JA (1988) Two groups of interrelated gene regulate early neurogenesis in Drosophila melanogaster. Roux's Arch Dev Biol 197:457–470

    Google Scholar 

  • Cabrera CV, Martinez-Arias A, Bate M (1987) The expression of three members of the achaete-scute gene complex correlates with neuroblast segregation in Drosophila. Cell 50:425–433

    Google Scholar 

  • Cagan RL, Ready DF (1989) Notch is required for successive cell decisions in the developing Drosophila eye. Genes Dev (in press)

  • Campos-Ortega JA (1980) On compound eye development in Drosophila melanogaster. Curr Top Dev Biol 15:347–371

    Google Scholar 

  • Campos-Ortega JA (1988) Cellular interactions during early neurogenesis of Drosophila melanogaster. Trends Neurosci 11:400–405

    Google Scholar 

  • Campos-Ortega JA, Hartenstein V (1985) The embryonic development of Drosophila melanogaster. Springer, Berlin Heidelberg New York Tokyo, pp 227

    Google Scholar 

  • Caudy M, Grell EH, Dambly-Chaudière C, Ghysen A, Jan LY, Jan YN (1988a) The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila. Genes Dev 2:843–852

    Google Scholar 

  • Caudy M, Vässin H, Brand M, Tuma R, Jan LY, Jan YN (1988b) daughterless, a gene essential for both neurogenesis and sex determination in Drosophila, has sequence similarities to myc and the achaete-scute complex. Cell 55:1061–1067

    Google Scholar 

  • Cavener DR, Otteson DC, Kaufman TC (1986) A rehabilitation of the genetic map of the 84B-D region of Drosophila melanogaster. Genetics 114:111–123

    Google Scholar 

  • Dambly-Chaudiàre C, Ghysen A, Jan LY, Jan YN (1988) The determination of sense organs in Drosophila: interactions of scute with daughterless. Roux's Arch Dev Biol 197:419–423

    Google Scholar 

  • de la Concha A, Dietrich U, Weigel D, Campos-Ortega JA (1988) Functional interactions of neurogenic genes of Drosophila melanogaster. Genetics 118:499–508

    Google Scholar 

  • Dietrich U, Campos-Ortega JA (1984) The expression of neurogenic loci in imaginal epidermal cells of Drosophila melanogaster. J Neurogenet 1:315–332

    Google Scholar 

  • Doe CQ, Goodman CS (1985) Early events in insect neurogenesis. II. The role of cell interactions and cell lineages in the determination of neuronal precursor cells. Dev Biol 111:206–219

    Google Scholar 

  • Dressler GR, Gruss P (1988) Do multigene families regulate vertebrate development? Trends Genet 4:214–219

    Google Scholar 

  • Fujita SC, Zipursky SL, Benzer S, Ferrus A, Shotwell SL (1982) Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci USA 79:7929–7933

    Google Scholar 

  • Harris WA, Starck WS (1977) Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process. J Gen Physiol 69:261–291

    Google Scholar 

  • Hartenstein V, Campos-Ortega JA (1984) Early neurogenesis in wildtype Drosophila melanogaster. Wilhelm Roux's Arch 193:308–325

    Google Scholar 

  • Hartley DA, Xu T, Artavanis-Tsakonas S (1987) The embryonic expression of the Notch locus of Drosophila melanogaster and the implications of point mutations in the extracellular EGF-like domain of the predicted protein. EMBO J 6:3407–3417

    Google Scholar 

  • Hazelrigg TI, Kaufman TC (1983) Revertants of dominant mutations associated with the Antennapedia gene complex of Drosophila melanogaster: cytology and genetics. Genetics 105:581–600

    Google Scholar 

  • Jarvik J, Botstein D (1975) Conditional-lethal mutations that suppress genetic defects in morphogenesis by altering structural proteins. Proc Natl Acad Sci USA 72:2738–2742

    Google Scholar 

  • Jimenez F, Campos-Ortega JA (1979) A region of the Drosophila genome necessary for CNS development. Nature 282:310–312

    Google Scholar 

  • Jimenez F, Campos-Ortega JA (1987) Genes in subdivision 1B of the Drosophila melanogaster X-chromosome and their influence on neural development. J Neurogenet 4:179–200

    Google Scholar 

  • Johansen KM, Fehon RG, Artavanis-Tsakonas S (1989) The Notch gene product is a glycoprotein expressed on the cell surface of both epidermal and neuronal precursor cells during Drosophila development. J Cell Biol 109:2427–2440

    Google Scholar 

  • Kelley MR, Kidd S, Deutsch WA, Young MW (1987) Mutations altering the structure of epidermal growth factor-like coding sequences at the Drosophila Notch locus. Cell 51:539–548

    Google Scholar 

  • Kerridge S, Thomas-Cavallin M (1988) Appendage morphogenesis in Drosophila: a developmental study of the rotund (rn) gene. 197:19–26

    Google Scholar 

  • Kidd S, Kelley MR, Young MW (1986) Sequence of the Notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. Mol Cell Biol 6:3094–3108

    Google Scholar 

  • Kidd S, Baylies MK, Gasic GP, Young MW (1989) Structure and distribution of the Notch protein in developing Drosophila. Genes Dev 3, 1113–1129

    Google Scholar 

  • Klämbt C, Knust E, Tietze K, Campos-Ortega JA (1989) Closely related transcripts encoded by the neurogenic gene complex Enhancer of split of Drosophila melanogaster. EMBO J 8:203–210

    Google Scholar 

  • Knust E, Bremer KA, Vässin H, Ziemer A, Tepaß U, Campos-Ortega JA (1987a) The Enhancer of split locus and neurogenesis in Drosophila melanogaster. Dev Biol 122:262–273

    Google Scholar 

  • Knust E, Tietze K, Campos-Ortega JA (1987b) Molecular analysis of the neurogenic locus Enhancer of split of Drosophila melanogaster. EMBO J 6:4113–4123

    Google Scholar 

  • Lehmann R, Jimenez F, Dietrich U, Campos-Ortega JA (1983) On the phenotype and development of mutants of early neurogenesis in Drosophila melanogaster. Wilhelm Roux's Arch 192:62–74

    Google Scholar 

  • Lewis EB, Bacher F (1968) Method of feeding ethyl methanesulfonate (EMS) to Drosophila males. Drosophila Information Service 43:193

    Google Scholar 

  • Lindsley DL, Grell EH (1968) Genetic variations of Drosophila melanogaster. Carnegie Inst Publ, Washington

    Google Scholar 

  • Maine EM, Kimble J (1989) Identification of genes that interact with glp-1, a gene required for inductive cell interactions in Caenorhabditis elegans. Development 105:133–143

    Google Scholar 

  • Meyerowitz EM, Kankel DR (1978) A genetic analysis of visual system development in Drosophila melanogaster. Dev Biol 62:112–142

    Google Scholar 

  • Moses K, Ellis MC, Rubin GM (1989) The glass gene encodes a zinc-finger protein required by Drosophila photoreceptor cells. Nature 340:531–536

    Google Scholar 

  • Murre C, McCaw PS, Vaessin H, Caudy M, Jan LY, Jan YN, Cabrera CV, Buskin JN, Hauschka SD, Lassar AB, Weintraub H, Baltimore D (1989) Interactions between heterologous helixloop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58:537–544

    Google Scholar 

  • Nüsslein-Vollhard C, Wieschaus E, Kluding H (1984) Mutations affecting the pattern of the larval cuticle of Drosophila melanogaster. I. Zygotic loci on the second chromosome. Wilhelm Roux's Arch 193:267–282

    Google Scholar 

  • Poulson DF (1937) Chromosomal deficiencies and embryonic development of Drosophila melanogaster. Proc Natl Acad Sci USA 23:133–137

    Google Scholar 

  • Sandler L (1977) Evidence for a set of closely linked autosomal genes that interact with sex-chromosome heterochromatin in Drosophila melanogaster. Genetics 86:567–582

    Google Scholar 

  • Shellenbarger DL, Mohler JD (1975) Temperature-sensitive mutations of the Notch locus in Drosophila melanogaster. Genetics 81:143–162

    Google Scholar 

  • Shellenbarger DL, Mohler JD (1978) Temperature-sensitive periods and autonomy of pleiotropic effects of l(1)N ts, a conditional Notch lethal in Drosophila. Dev Biol 62:432–446

    Google Scholar 

  • Shepard SB, Broverman SA, Muskavitch MAT (1989) A tripartite interaction among alleles of Notch, Delta and Enhancer of split during imaginal development of Drosophila melanogaster. Genetics 122:429–438

    Google Scholar 

  • Technau GM, Campos-Ortega JA (1985) Fate mapping in wildtype Drosophila melanogaster. II. Injections of horseradish peroxidase in cells of the early gastrula stage. Roux's Arch Dev Biol 194:196–212

    Google Scholar 

  • Technau GM, Campos-Ortega JA (1986) Lineage analysis of transplanted individual cells in embryos of Drosophila melanogaster. II. Commitment and proliferative capabilities of neural and epidermal cell progenitors. Wilhelm Roux's Arch 195:445–454

    Google Scholar 

  • Technau GM, Campos-Ortega JA (1987) Cell autonomy of expression of neurogenic genes of Drosophila melanogaster. Proc Natl Acad Sci USA 84:4500–4504

    Google Scholar 

  • Vässin H, Campos-Ortega JA (1987) Genetic analysis of Delta, a neurogenic gene of Drosophila melanogaster. Genetics 116:433–445

    Google Scholar 

  • Vässin H, Vielmetter J, Campos-Ortega JA (1985) Genetic interactions in early neurogenesis of Drosophila melanogaster. J Neurogen 2:291–308

    Google Scholar 

  • Vässin H, Bremer KA, Knust E, Campos-Ortega JA (1987) The neurogenic locust Delta of Drosophila melanogaster is expressed in neurogenic territories and encodes a putative transmembrane protein with EGF-like repeats. EMBO J 6:3431–3440

    Google Scholar 

  • Weigel D, Knust E, Campos-Ortega JA (1987) Molecular organization of master mind, a neurogenic gene of Drosophila melanogaster. Mol Gen Genet 207:374–384

    Google Scholar 

  • Welshons WJ (1956) Dosage experiments with split mutants in the presence of an enhancer of split. Drosophila Information Service 30:157–158

    Google Scholar 

  • Wharton KA, Johansen KM, Xu T, Artavanis-Tsakonas S (1985) Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43:567–581

    Google Scholar 

  • White K (1980) Defective neural development in Drosophila melanogaster embryos deficient for the tip of the X-chromosome. Dev Biol 80:322–344

    Google Scholar 

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  1. Michael Brand

    Present address: Howard Hughes Medical Institute and Department of Physiology and Biochemistry, University of California, San Francisco, California, USA

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  1. Institut für Entwicklungsphysiologie, Universität Köln, Gyrhofstrasse 17, D-5000, Köln 41, Federal Republic of Germany

    Michael Brand & José A. Campos-Ortega

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  1. Michael Brand
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  2. José A. Campos-Ortega
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Brand, M., Campos-Ortega, J.A. Second-site modifiers of the split mutation of Notch define genes involved in neurogenesis in Drosophila melanogaster . Roux's Arch Dev Biol 198, 275–285 (1990). https://doi.org/10.1007/BF00377394

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