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. 2002 Feb;160(2):623–635. doi: 10.1093/genetics/160.2.623

Rough eye is a gain-of-function allele of amos that disrupts regulation of the proneural gene atonal during Drosophila retinal differentiation.

Françoise Chanut 1, Katherine Woo 1, Shalini Pereira 1, Terrence J Donohoe 1, Shang-Yu Chang 1, Todd R Laverty 1, Andrew P Jarman 1, Ulrike Heberlein 1
PMCID: PMC1461986  PMID: 11861566

Abstract

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.

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Selected References

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  1. Adams M. D., Celniker S. E., Holt R. A., Evans C. A., Gocayne J. D., Amanatides P. G., Scherer S. E., Li P. W., Hoskins R. A., Galle R. F. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. doi: 10.1126/science.287.5461.2185. [DOI] [PubMed] [Google Scholar]
  2. Ashburner M., Misra S., Roote J., Lewis S. E., Blazej R., Davis T., Doyle C., Galle R., George R., Harris N. An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 1999 Sep;153(1):179–219. doi: 10.1093/genetics/153.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashburner M., Thompson P., Roote J., Lasko P. F., Grau Y., el Messal M., Roth S., Simpson P. 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. Genetics. 1990 Nov;126(3):679–694. doi: 10.1093/genetics/126.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker N. E., Mlodzik M., Rubin G. M. Spacing differentiation in the developing Drosophila eye: a fibrinogen-related lateral inhibitor encoded by scabrous. Science. 1990 Dec 7;250(4986):1370–1377. doi: 10.1126/science.2175046. [DOI] [PubMed] [Google Scholar]
  5. Baker N. E., Rubin G. M. Ellipse mutations in the Drosophila homologue of the EGF receptor affect pattern formation, cell division, and cell death in eye imaginal discs. Dev Biol. 1992 Apr;150(2):381–396. doi: 10.1016/0012-1606(92)90250-k. [DOI] [PubMed] [Google Scholar]
  6. Baker N. E., Yu S., Han D. Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye. Curr Biol. 1996 Oct 1;6(10):1290–1301. doi: 10.1016/s0960-9822(02)70715-x. [DOI] [PubMed] [Google Scholar]
  7. Blackman R. K., Grimaila R., Koehler M. M., Gelbart W. M. Mobilization of hobo elements residing within the decapentaplegic gene complex: suggestion of a new hybrid dysgenesis system in Drosophila melanogaster. Cell. 1987 May 22;49(4):497–505. doi: 10.1016/0092-8674(87)90452-1. [DOI] [PubMed] [Google Scholar]
  8. Blackman R. K., Sanicola M., Raftery L. A., Gillevet T., Gelbart W. M. An extensive 3' cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-beta family in Drosophila. Development. 1991 Mar;111(3):657–666. doi: 10.1242/dev.111.3.657. [DOI] [PubMed] [Google Scholar]
  9. Borod E. R., Heberlein U. Mutual regulation of decapentaplegic and hedgehog during the initiation of differentiation in the Drosophila retina. Dev Biol. 1998 May 15;197(2):187–197. doi: 10.1006/dbio.1998.8888. [DOI] [PubMed] [Google Scholar]
  10. Brand A. H., Manoukian A. S., Perrimon N. Ectopic expression in Drosophila. Methods Cell Biol. 1994;44:635–654. doi: 10.1016/s0091-679x(08)60936-x. [DOI] [PubMed] [Google Scholar]
  11. Brennan C. A., Moses K. Determination of Drosophila photoreceptors: timing is everything. Cell Mol Life Sci. 2000 Feb;57(2):195–214. doi: 10.1007/PL00000684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brown N. L., Sattler C. A., Paddock S. W., Carroll S. B. Hairy and emc negatively regulate morphogenetic furrow progression in the Drosophila eye. Cell. 1995 Mar 24;80(6):879–887. doi: 10.1016/0092-8674(95)90291-0. [DOI] [PubMed] [Google Scholar]
  13. Cagan R. L., Krämer H., Hart A. C., Zipursky S. L. The bride of sevenless and sevenless interaction: internalization of a transmembrane ligand. Cell. 1992 May 1;69(3):393–399. doi: 10.1016/0092-8674(92)90442-f. [DOI] [PubMed] [Google Scholar]
  14. Cagan R. L., Ready D. F. Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev. 1989 Aug;3(8):1099–1112. doi: 10.1101/gad.3.8.1099. [DOI] [PubMed] [Google Scholar]
  15. Cagan R. Cell fate specification in the developing Drosophila retina. Dev Suppl. 1993:19–28. [PubMed] [Google Scholar]
  16. Caudy M., Vässin H., Brand M., Tuma R., Jan L. Y., Jan Y. N. daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell. 1988 Dec 23;55(6):1061–1067. doi: 10.1016/0092-8674(88)90250-4. [DOI] [PubMed] [Google Scholar]
  17. Chanut F., Heberlein U. Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina. Development. 1997 Jan;124(2):559–567. doi: 10.1242/dev.124.2.559. [DOI] [PubMed] [Google Scholar]
  18. Chanut F., Luk A., Heberlein U. 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. Genetics. 2000 Nov;156(3):1203–1217. doi: 10.1093/genetics/156.3.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Chen R., Amoui M., Zhang Z., Mardon G. Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell. 1997 Dec 26;91(7):893–903. doi: 10.1016/s0092-8674(00)80481-x. [DOI] [PubMed] [Google Scholar]
  20. Dokucu M. E., Zipursky S. L., Cagan R. L. Atonal, rough and the resolution of proneural clusters in the developing Drosophila retina. Development. 1996 Dec;122(12):4139–4147. doi: 10.1242/dev.122.12.4139. [DOI] [PubMed] [Google Scholar]
  21. Domínguez M., Hafen E. Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosophila eye. Genes Dev. 1997 Dec 1;11(23):3254–3264. doi: 10.1101/gad.11.23.3254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Freeman M. Cell determination strategies in the Drosophila eye. Development. 1997 Jan;124(2):261–270. doi: 10.1242/dev.124.2.261. [DOI] [PubMed] [Google Scholar]
  23. Freeman M. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell. 1996 Nov 15;87(4):651–660. doi: 10.1016/s0092-8674(00)81385-9. [DOI] [PubMed] [Google Scholar]
  24. Goulding S. E., zur Lage P., Jarman A. P. amos, a proneural gene for Drosophila olfactory sense organs that is regulated by lozenge. Neuron. 2000 Jan;25(1):69–78. doi: 10.1016/s0896-6273(00)80872-7. [DOI] [PubMed] [Google Scholar]
  25. Heanue T. A., Reshef R., Davis R. J., Mardon G., Oliver G., Tomarev S., Lassar A. B., Tabin C. J. Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes Dev. 1999 Dec 15;13(24):3231–3243. doi: 10.1101/gad.13.24.3231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Heberlein U., Mlodzik M., Rubin G. M. Cell-fate determination in the developing Drosophila eye: role of the rough gene. Development. 1991 Jul;112(3):703–712. doi: 10.1242/dev.112.3.703. [DOI] [PubMed] [Google Scholar]
  27. Heberlein U., Moses K. Mechanisms of Drosophila retinal morphogenesis: the virtues of being progressive. Cell. 1995 Jun 30;81(7):987–990. doi: 10.1016/s0092-8674(05)80003-0. [DOI] [PubMed] [Google Scholar]
  28. Heberlein U., Wolff T., Rubin G. M. The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell. 1993 Dec 3;75(5):913–926. doi: 10.1016/0092-8674(93)90535-x. [DOI] [PubMed] [Google Scholar]
  29. Horsfield J., Penton A., Secombe J., Hoffman F. M., Richardson H. decapentaplegic is required for arrest in G1 phase during Drosophila eye development. Development. 1998 Dec;125(24):5069–5078. doi: 10.1242/dev.125.24.5069. [DOI] [PubMed] [Google Scholar]
  30. Huang M. L., Hsu C. H., Chien C. T. The proneural gene amos promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system. Neuron. 2000 Jan;25(1):57–67. doi: 10.1016/s0896-6273(00)80871-5. [DOI] [PubMed] [Google Scholar]
  31. Huang Y., Fischer-Vize J. A. Undifferentiated cells in the developing Drosophila eye influence facet assembly and require the Fat facets ubiquitin-specific protease. Development. 1996 Oct;122(10):3207–3216. doi: 10.1242/dev.122.10.3207. [DOI] [PubMed] [Google Scholar]
  32. Jarman A. P., Grau Y., Jan L. Y., Jan Y. N. atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell. 1993 Jul 2;73(7):1307–1321. doi: 10.1016/0092-8674(93)90358-w. [DOI] [PubMed] [Google Scholar]
  33. Jarman A. P., Grell E. H., Ackerman L., Jan L. Y., Jan Y. N. Atonal is the proneural gene for Drosophila photoreceptors. Nature. 1994 Jun 2;369(6479):398–400. doi: 10.1038/369398a0. [DOI] [PubMed] [Google Scholar]
  34. Kawamura K., Shibata T., Saget O., Peel D., Bryant P. J. A new family of growth factors produced by the fat body and active on Drosophila imaginal disc cells. Development. 1999 Jan;126(2):211–219. doi: 10.1242/dev.126.2.211. [DOI] [PubMed] [Google Scholar]
  35. Kopczynski C. C., Alton A. K., Fechtel K., Kooh P. J., Muskavitch M. A. Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates. Genes Dev. 1988 Dec;2(12B):1723–1735. doi: 10.1101/gad.2.12b.1723. [DOI] [PubMed] [Google Scholar]
  36. Krämer H., Cagan R. L., Zipursky S. L. Interaction of bride of sevenless membrane-bound ligand and the sevenless tyrosine-kinase receptor. Nature. 1991 Jul 18;352(6332):207–212. doi: 10.1038/352207a0. [DOI] [PubMed] [Google Scholar]
  37. Kumar J., Moses K. Transcription factors in eye development: a gorgeous mosaic? Genes Dev. 1997 Aug 15;11(16):2023–2028. doi: 10.1101/gad.11.16.2023. [DOI] [PubMed] [Google Scholar]
  38. Lee J. J., von Kessler D. P., Parks S., Beachy P. A. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 1992 Oct 2;71(1):33–50. doi: 10.1016/0092-8674(92)90264-d. [DOI] [PubMed] [Google Scholar]
  39. Ma C., Zhou Y., Beachy P. A., Moses K. The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye. Cell. 1993 Dec 3;75(5):927–938. doi: 10.1016/0092-8674(93)90536-y. [DOI] [PubMed] [Google Scholar]
  40. Mardon G., Solomon N. M., Rubin G. M. dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development. 1994 Dec;120(12):3473–3486. doi: 10.1242/dev.120.12.3473. [DOI] [PubMed] [Google Scholar]
  41. Penton A., Selleck S. B., Hoffmann F. M. Regulation of cell cycle synchronization by decapentaplegic during Drosophila eye development. Science. 1997 Jan 10;275(5297):203–206. doi: 10.1126/science.275.5297.203. [DOI] [PubMed] [Google Scholar]
  42. Pignoni F., Hu B., Zavitz K. H., Xiao J., Garrity P. A., Zipursky S. L. The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell. 1997 Dec 26;91(7):881–891. doi: 10.1016/s0092-8674(00)80480-8. [DOI] [PubMed] [Google Scholar]
  43. Powell P. A., Wesley C., Spencer S., Cagan R. L. Scabrous complexes with Notch to mediate boundary formation. Nature. 2001 Feb 1;409(6820):626–630. doi: 10.1038/35054566. [DOI] [PubMed] [Google Scholar]
  44. Ready D. F., Hanson T. E., Benzer S. Development of the Drosophila retina, a neurocrystalline lattice. Dev Biol. 1976 Oct 15;53(2):217–240. doi: 10.1016/0012-1606(76)90225-6. [DOI] [PubMed] [Google Scholar]
  45. Renfranz P. J., Benzer S. Monoclonal antibody probes discriminate early and late mutant defects in development of the Drosophila retina. Dev Biol. 1989 Dec;136(2):411–429. doi: 10.1016/0012-1606(89)90267-4. [DOI] [PubMed] [Google Scholar]
  46. Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Rubin G. M., Yandell M. D., Wortman J. R., Gabor Miklos G. L., Nelson C. R., Hariharan I. K., Fortini M. E., Li P. W., Apweiler R., Fleischmann W. Comparative genomics of the eukaryotes. Science. 2000 Mar 24;287(5461):2204–2215. doi: 10.1126/science.287.5461.2204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Schüpbach T., Wieschaus E. Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology. Genetics. 1991 Dec;129(4):1119–1136. doi: 10.1093/genetics/129.4.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Staehling-Hampton K., Jackson P. D., Clark M. J., Brand A. H., Hoffmann F. M. Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A. Cell Growth Differ. 1994 Jun;5(6):585–593. [PubMed] [Google Scholar]
  50. Strutt D. I., Mlodzik M. Hedgehog is an indirect regulator of morphogenetic furrow progression in the Drosophila eye disc. Development. 1997 Sep;124(17):3233–3240. doi: 10.1242/dev.124.17.3233. [DOI] [PubMed] [Google Scholar]
  51. Sun Y., Jan L. Y., Jan Y. N. Ectopic scute induces Drosophila ommatidia development without R8 founder photoreceptors. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6815–6819. doi: 10.1073/pnas.110154497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sun Y., Jan L. Y., Jan Y. N. Transcriptional regulation of atonal during development of the Drosophila peripheral nervous system. Development. 1998 Sep;125(18):3731–3740. doi: 10.1242/dev.125.18.3731. [DOI] [PubMed] [Google Scholar]
  53. Thomas B. J., Gunning D. A., Cho J., Zipursky L. Cell cycle progression in the developing Drosophila eye: roughex encodes a novel protein required for the establishment of G1. Cell. 1994 Jul 1;77(7):1003–1014. doi: 10.1016/0092-8674(94)90440-5. [DOI] [PubMed] [Google Scholar]
  54. Tomlinson A., Bowtell D. D., Hafen E., Rubin G. M. Localization of the sevenless protein, a putative receptor for positional information, in the eye imaginal disc of Drosophila. Cell. 1987 Oct 9;51(1):143–150. doi: 10.1016/0092-8674(87)90019-5. [DOI] [PubMed] [Google Scholar]
  55. Tomlinson A., Kimmel B. E., Rubin G. M. rough, a Drosophila homeobox gene required in photoreceptors R2 and R5 for inductive interactions in the developing eye. Cell. 1988 Dec 2;55(5):771–784. doi: 10.1016/0092-8674(88)90133-x. [DOI] [PubMed] [Google Scholar]
  56. Tomlinson A., Ready D. F. Cell fate in the Drosophila ommatidium. Dev Biol. 1987 Sep;123(1):264–275. doi: 10.1016/0012-1606(87)90448-9. [DOI] [PubMed] [Google Scholar]
  57. Tomlinson A., Ready D. F. Neuronal differentiation in Drosophila ommatidium. Dev Biol. 1987 Apr;120(2):366–376. doi: 10.1016/0012-1606(87)90239-9. [DOI] [PubMed] [Google Scholar]
  58. Tomlinson A. The cellular dynamics of pattern formation in the eye of Drosophila. J Embryol Exp Morphol. 1985 Oct;89:313–331. [PubMed] [Google Scholar]
  59. Wharton K. A., Johansen K. M., Xu T., Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell. 1985 Dec;43(3 Pt 2):567–581. doi: 10.1016/0092-8674(85)90229-6. [DOI] [PubMed] [Google Scholar]
  60. White N. M., Jarman A. P. Drosophila atonal controls photoreceptor R8-specific properties and modulates both receptor tyrosine kinase and Hedgehog signalling. Development. 2000 Apr;127(8):1681–1689. doi: 10.1242/dev.127.8.1681. [DOI] [PubMed] [Google Scholar]
  61. Wright T. R., Hodgetts R. B., Sherald A. F. The genetics of dopa decarboxylase in Drosophila melanogaster. I. Isolation and characterization of deficiencies that delete the dopa-decarboxylase-dosage-sensitive region and the alpha-methyl-dopa-hypersensitive locus. Genetics. 1976 Oct;84(2):267–285. doi: 10.1093/genetics/84.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Zinn K., McAllister L., Goodman C. S. Sequence analysis and neuronal expression of fasciclin I in grasshopper and Drosophila. Cell. 1988 May 20;53(4):577–587. doi: 10.1016/0092-8674(88)90574-0. [DOI] [PubMed] [Google Scholar]

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