Skip to main content
Genetics logoLink to Genetics
. 1998 Mar;148(3):1189–1201. doi: 10.1093/genetics/148.3.1189

Genetic analysis of Drosophila larval optic nerve development.

A L Holmes 1, R N Raper 1, J S Heilig 1
PMCID: PMC1460051  PMID: 9539434

Abstract

To identify genes necessary for establishing connections in the Drosophila sensory nervous system, we designed a screen for mutations affecting development of the larval visual system. The larval visual system has a simple and stereotypic morphology, can be recognized histologically by a variety of techniques, and is unnecessary for viability. Therefore, it provides an opportunity to identify genes involved in all stages of development of a simple, specific neuronal connection. By direct observation of the larval visual system in mutant embryos, we identified 24 mutations affecting its development; 13 of these are larval visual system-specific. These 13 mutations can be grouped phenotypically into five classes based on their effects on location, path or morphology of the larval visual system nerves and organs. These mutants and phenotypic classifications provide a context for further analysis of neuronal development, pathfinding and target recognition.

Full Text

The Full Text of this article is available as a PDF (825.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bellen H. J., O'Kane C. J., Wilson C., Grossniklaus U., Pearson R. K., Gehring W. J. P-element-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev. 1989 Sep;3(9):1288–1300. doi: 10.1101/gad.3.9.1288. [DOI] [PubMed] [Google Scholar]
  2. Bentley D., Keshishian H. Pathfinding by peripheral pioneer neurons in grasshoppers. Science. 1982 Dec 10;218(4577):1082–1088. doi: 10.1126/science.218.4577.1082. [DOI] [PubMed] [Google Scholar]
  3. Bonhoeffer F., Huf J. Position-dependent properties of retinal axons and their growth cones. 1985 May 30-Jun 5Nature. 315(6018):409–410. doi: 10.1038/315409a0. [DOI] [PubMed] [Google Scholar]
  4. Cheng H. J., Nakamoto M., Bergemann A. D., Flanagan J. G. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell. 1995 Aug 11;82(3):371–381. doi: 10.1016/0092-8674(95)90426-3. [DOI] [PubMed] [Google Scholar]
  5. Cheyette B. N., Green P. J., Martin K., Garren H., Hartenstein V., Zipursky S. L. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron. 1994 May;12(5):977–996. doi: 10.1016/0896-6273(94)90308-5. [DOI] [PubMed] [Google Scholar]
  6. Chiba A., Snow P., Keshishian H., Hotta Y. Fasciclin III as a synaptic target recognition molecule in Drosophila. Nature. 1995 Mar 9;374(6518):166–168. doi: 10.1038/374166a0. [DOI] [PubMed] [Google Scholar]
  7. Colamarino S. A., Tessier-Lavigne M. The axonal chemoattractant netrin-1 is also a chemorepellent for trochlear motor axons. Cell. 1995 May 19;81(4):621–629. doi: 10.1016/0092-8674(95)90083-7. [DOI] [PubMed] [Google Scholar]
  8. Drescher U., Kremoser C., Handwerker C., Löschinger J., Noda M., Bonhoeffer F. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell. 1995 Aug 11;82(3):359–370. doi: 10.1016/0092-8674(95)90425-5. [DOI] [PubMed] [Google Scholar]
  9. Fambrough D., Goodman C. S. The Drosophila beaten path gene encodes a novel secreted protein that regulates defasciculation at motor axon choice points. Cell. 1996 Dec 13;87(6):1049–1058. doi: 10.1016/s0092-8674(00)81799-7. [DOI] [PubMed] [Google Scholar]
  10. Fambrough D., Pan D., Rubin G. M., Goodman C. S. The cell surface metalloprotease/disintegrin Kuzbanian is required for axonal extension in Drosophila. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13233–13238. doi: 10.1073/pnas.93.23.13233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujita S. C., Zipursky S. L., Benzer S., Ferrús A., Shotwell S. L. Monoclonal antibodies against the Drosophila nervous system. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7929–7933. doi: 10.1073/pnas.79.24.7929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goodman C. S., Shatz C. J. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell. 1993 Jan;72 (Suppl):77–98. doi: 10.1016/s0092-8674(05)80030-3. [DOI] [PubMed] [Google Scholar]
  13. Green P., Hartenstein A. Y., Hartenstein V. The embryonic development of the Drosophila visual system. Cell Tissue Res. 1993 Sep;273(3):583–598. doi: 10.1007/BF00333712. [DOI] [PubMed] [Google Scholar]
  14. Grenningloh G., Rehm E. J., Goodman C. S. Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule. Cell. 1991 Oct 4;67(1):45–57. doi: 10.1016/0092-8674(91)90571-f. [DOI] [PubMed] [Google Scholar]
  15. Jan L. Y., Jan Y. N. Antibodies to horseradish peroxidase as specific neuronal markers in Drosophila and in grasshopper embryos. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2700–2704. doi: 10.1073/pnas.79.8.2700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jay D. G., Keshishian H. Laser inactivation of fasciclin I disrupts axon adhesion of grasshopper pioneer neurons. Nature. 1990 Dec 6;348(6301):548–550. doi: 10.1038/348548a0. [DOI] [PubMed] [Google Scholar]
  17. Kennedy T. E., Serafini T., de la Torre J. R., Tessier-Lavigne M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell. 1994 Aug 12;78(3):425–435. doi: 10.1016/0092-8674(94)90421-9. [DOI] [PubMed] [Google Scholar]
  18. Kunes S., Steller H. Ablation of Drosophila photoreceptor cells by conditional expression of a toxin gene. Genes Dev. 1991 Jun;5(6):970–983. doi: 10.1101/gad.5.6.970. [DOI] [PubMed] [Google Scholar]
  19. Lin D. M., Fetter R. D., Kopczynski C., Grenningloh G., Goodman C. S. Genetic analysis of Fasciclin II in Drosophila: defasciculation, refasciculation, and altered fasciculation. Neuron. 1994 Nov;13(5):1055–1069. doi: 10.1016/0896-6273(94)90045-0. [DOI] [PubMed] [Google Scholar]
  20. Lis J. T., Simon J. A., Sutton C. A. New heat shock puffs and beta-galactosidase activity resulting from transformation of Drosophila with an hsp70-lacZ hybrid gene. Cell. 1983 Dec;35(2 Pt 1):403–410. doi: 10.1016/0092-8674(83)90173-3. [DOI] [PubMed] [Google Scholar]
  21. Luo Y., Raible D., Raper J. A. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell. 1993 Oct 22;75(2):217–227. doi: 10.1016/0092-8674(93)80064-l. [DOI] [PubMed] [Google Scholar]
  22. Luo Y., Shepherd I., Li J., Renzi M. J., Chang S., Raper J. A. A family of molecules related to collapsin in the embryonic chick nervous system. Neuron. 1995 Jun;14(6):1131–1140. doi: 10.1016/0896-6273(95)90261-9. [DOI] [PubMed] [Google Scholar]
  23. Martin K. A., Poeck B., Roth H., Ebens A. J., Ballard L. C., Zipursky S. L. Mutations disrupting neuronal connectivity in the Drosophila visual system. Neuron. 1995 Feb;14(2):229–240. doi: 10.1016/0896-6273(95)90281-3. [DOI] [PubMed] [Google Scholar]
  24. Mitchison T. J., Sedat J. Localization of antigenic determinants in whole Drosophila embryos. Dev Biol. 1983 Sep;99(1):261–264. doi: 10.1016/0012-1606(83)90275-0. [DOI] [PubMed] [Google Scholar]
  25. Moses K., Ellis M. C., Rubin G. M. The glass gene encodes a zinc-finger protein required by Drosophila photoreceptor cells. Nature. 1989 Aug 17;340(6234):531–536. doi: 10.1038/340531a0. [DOI] [PubMed] [Google Scholar]
  26. Moses K., Rubin G. M. Glass encodes a site-specific DNA-binding protein that is regulated in response to positional signals in the developing Drosophila eye. Genes Dev. 1991 Apr;5(4):583–593. doi: 10.1101/gad.5.4.583. [DOI] [PubMed] [Google Scholar]
  27. Palka J., Schubiger M., Ellison R. L. The polarity of axon growth in the wings of Drosophila melanogaster. Dev Biol. 1983 Aug;98(2):481–492. doi: 10.1016/0012-1606(83)90377-9. [DOI] [PubMed] [Google Scholar]
  28. SPERRY R. W. CHEMOAFFINITY IN THE ORDERLY GROWTH OF NERVE FIBER PATTERNS AND CONNECTIONS. Proc Natl Acad Sci U S A. 1963 Oct;50:703–710. doi: 10.1073/pnas.50.4.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schmucker D., Jäckle H., Gaul U. Genetic analysis of the larval optic nerve projection in Drosophila. Development. 1997 Mar;124(5):937–948. doi: 10.1242/dev.124.5.937. [DOI] [PubMed] [Google Scholar]
  30. Schmucker D., Su A. L., Beermann A., Jäckle H., Jay D. G. Chromophore-assisted laser inactivation of patched protein switches cell fate in the larval visual system of Drosophila. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2664–2668. doi: 10.1073/pnas.91.7.2664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schmucker D., Taubert H., Jäckle H. Formation of the Drosophila larval photoreceptor organ and its neuronal differentiation require continuous Krüppel gene activity. Neuron. 1992 Dec;9(6):1025–1039. doi: 10.1016/0896-6273(92)90063-j. [DOI] [PubMed] [Google Scholar]
  32. Seeger M., Tear G., Ferres-Marco D., Goodman C. S. Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron. 1993 Mar;10(3):409–426. doi: 10.1016/0896-6273(93)90330-t. [DOI] [PubMed] [Google Scholar]
  33. Serafini T., Kennedy T. E., Galko M. J., Mirzayan C., Jessell T. M., Tessier-Lavigne M. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell. 1994 Aug 12;78(3):409–424. doi: 10.1016/0092-8674(94)90420-0. [DOI] [PubMed] [Google Scholar]
  34. Simon J. A., Sutton C. A., Lobell R. B., Glaser R. L., Lis J. T. Determinants of heat shock-induced chromosome puffing. Cell. 1985 Apr;40(4):805–817. doi: 10.1016/0092-8674(85)90340-x. [DOI] [PubMed] [Google Scholar]
  35. Steller H., Fischbach K. F., Rubin G. M. Disconnected: a locus required for neuronal pathway formation in the visual system of Drosophila. Cell. 1987 Sep 25;50(7):1139–1153. doi: 10.1016/0092-8674(87)90180-2. [DOI] [PubMed] [Google Scholar]
  36. Tanaka E., Sabry J. Making the connection: cytoskeletal rearrangements during growth cone guidance. Cell. 1995 Oct 20;83(2):171–176. doi: 10.1016/0092-8674(95)90158-2. [DOI] [PubMed] [Google Scholar]
  37. Tix S., Minden J. S., Technau G. M. Pre-existing neuronal pathways in the developing optic lobes of Drosophila. Development. 1989 Apr;105(4):739–746. doi: 10.1242/dev.105.4.739. [DOI] [PubMed] [Google Scholar]
  38. Vactor D. V., Sink H., Fambrough D., Tsoo R., Goodman C. S. Genes that control neuromuscular specificity in Drosophila. Cell. 1993 Jun 18;73(6):1137–1153. doi: 10.1016/0092-8674(93)90643-5. [DOI] [PubMed] [Google Scholar]
  39. Zipursky S. L., Venkatesh T. R., Teplow D. B., Benzer S. Neuronal development in the Drosophila retina: monoclonal antibodies as molecular probes. Cell. 1984 Jan;36(1):15–26. doi: 10.1016/0092-8674(84)90069-2. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES