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  • Review Article
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Signalling pathways in Drosophila and vertebrate retinal development

Nature Reviews Genetics volume 2, pages 846–857 (2001)Cite this article

Key Points

  • The use of signal-transduction cascades in Drosophila eye specification indicates that retinal determination is an inductive process rather than a tissue-autonomous decision.

  • Manipulations of the Epidermal growth factor receptor and Notch signalling pathways result in homeotic eye-to-antenna transformations, indicating that the elusive master gene for fly eye specification might reside genetically upstream of these cascades.

  • The crucial period for Notch activity in eye specification and the expression patterns of the retinal determination genes indicate that the Drosophila eye might be specified during the second larval instar stage of development.

  • The use of common mechanisms and molecules in retinal patterning (Hedgehog) and founder cell selection (Atonal) indicates that the eye has a monophyletic origin.

Abstract

The near-catholic conservation of paired box gene 6 (Pax6) and its supporting cast of retinal determination genes throughout the animal kingdom has sparked a scientific war over the evolutionary origins of the eye. The battle pits those who support a polyphyletic history for the eye against those who argue for a common ancestor for all 'seeing' animals. Recent papers have shed light on how eyes in both vertebrates and invertebrates are patterned. New insights into the roles that signal-transduction cascades might have in determining the Drosophila melanogaster eye indicate that, like many developmental processes, eye specification is an inductive process.

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Figure 1: Genetic control of eye specification in Drosophila.
Figure 2: Egfr and Notch signalling control eye and antennal identity in Drosophila.
Figure 3: Hedgehog is required for neurogenesis and for atonal expression in the fly eye.
Figure 4: Sonic hedgehog expression across the zebrafish retina.
Figure 5: Mutations in the zebrafish homologue of atonal inhibit the first wave of neurogenesis in the developing retina.

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References

  1. Neumann, C. J. & Nuesslein-Volhard, C. Patterning of the zebrafish retina by a wave of Sonic hedgehog activity. Science 289, 2137–2139 (2000).Indicates that Hedgehog signalling might be used in patterning the vertebrate retina.

    CAS  PubMed  Google Scholar 

  2. Hsiao, F. C., Williams, A., Davies, E. L. & Rebay, I. Eyes absent mediates cross-talk between retinal determination genes and the receptor tyrosine kinase signaling pathway. Dev. Cell 1, 51–61 (2001).Shows that receptor tyrosine kinase signalling exerts a positive influence on Drosophila eye specification through the phosphorylation of the Eyes absent protein by Mitogen-activated protein kinase.

    CAS  PubMed  Google Scholar 

  3. Kumar, J. P. & Moses, K. EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. Cell 104, 687–697 (2001).Proposes that the Epidermal growth factor receptor and Notch signalling cascades have roles in Drosophila eye and antenna specification.

    CAS  PubMed  Google Scholar 

  4. Kurata, S., Go, M. J., Artavanis-Tsakonas, S. & Gehring, W. J. Notch signaling and the determination of appendage identity. Proc. Natl Acad. Sci. USA 97, 2117–2122 (2000).Indicates that Notch might have a role in signalling during appendage specification.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hunt, D. M. The physiological control of gene action in the eyeless and eyegone mutants of Drosophila melanogaster. Genet. Res. 17, 195–208 (1971).

    CAS  PubMed  Google Scholar 

  6. Bonini, N. M., Leiserson, W. M. & Benzer, S. The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 72, 379–395 (1993).

    CAS  PubMed  Google Scholar 

  7. Cheyette, B. N. et al. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron 12, 977–996 (1994).

    CAS  PubMed  Google Scholar 

  8. Mardon, G., Solomon, N. M. & Rubin, G. M. dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development 120, 3473–3486 (1994).

    CAS  PubMed  Google Scholar 

  9. Quiring, R., Walldorf, U., Kloter, U. & Gehring, W. J. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785–789 (1994).

    CAS  PubMed  Google Scholar 

  10. Serikaku, M. A. & O'Tousa, J. E. sine oculis is a homeobox gene required for Drosophila visual system development. Genetics 138, 1137–1150 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hazelett, D. J., Bourouis, M., Walldorf, U. & Treisman, J. E. decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc. Development 125, 3741–3751 (1998).

    CAS  PubMed  Google Scholar 

  12. Czerny, T. et al. twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol. Cell 3, 297–307 (1999).

    CAS  PubMed  Google Scholar 

  13. Seimiya, M. & Gehring, W. J. The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism. Development 127, 1879–1886 (2000).

    CAS  PubMed  Google Scholar 

  14. 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 91, 893–903 (1997).

    CAS  PubMed  Google Scholar 

  15. Halder, G. et al. Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125, 2181–2191 (1998).

    CAS  PubMed  Google Scholar 

  16. Niimi, T., Seimiya, M., Kloter, U., Flister, S. & Gehring, W. J. Direct regulatory interaction of the Eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila. Development 126, 2253–2260 (1999).

    CAS  PubMed  Google Scholar 

  17. Hunt, D. M. Lethal interactions of the eye-gone and eyeless mutants in Drosophila melanogaster. Genet. Res. 15, 29–34 (1970).

    CAS  PubMed  Google Scholar 

  18. Bui, Q. T., Zimmerman, J. E., Liu, H., Gray-Board, G. L. & Bonini, N. M. Functional analysis of an eye enhancer of the Drosophila eyes absent gene: differential regulation by eye specification genes. Dev. Biol. 221, 355–364 (2000).

    CAS  PubMed  Google Scholar 

  19. Zimmerman, J. E., Bui, Q. T., Liu, H. & Bonini, N. M. Molecular genetic analysis of Drosophila eyes absent mutants reveals an eye enhancer element. Genetics 154, 237–246 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Pignoni, F. et al. The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 91, 881–891 (1997).

    CAS  PubMed  Google Scholar 

  21. Pan, D. & Rubin, G. M. Targeted expression of teashirt induces ectopic eyes in Drosophila. Proc. Natl Acad. Sci. USA 95, 15508–15512 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Pichaud, F. & Casares, F. homothorax and iroquois-C genes are required for the establishment of territories within the developing eye disc. Mech. Dev. 96, 15–25 (2000).

    CAS  PubMed  Google Scholar 

  23. Jaw, T. J. et al. Direct interaction of two homeoproteins, homothorax and extradenticle, is essential for EXD nuclear localization and function. Mech. Dev. 91, 279–291 (2000).

    CAS  PubMed  Google Scholar 

  24. Chen, R., Halder, G., Zhang, Z. & Mardon, G. Signaling by the TGF-β homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila. Development 126, 935–943 (1999).

    CAS  PubMed  Google Scholar 

  25. Curtiss, J. & Mlodzik, M. Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent. Development 127, 1325–1336 (2000).

    CAS  PubMed  Google Scholar 

  26. Bonini, N. M., Bui, Q. T., Gray-Board, G. L. & Warrick, J. M. The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 124, 4819–4826 (1997).

    CAS  PubMed  Google Scholar 

  27. Halder, G., Callaerts, P. & Gehring, W. J. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267, 1788–1792 (1995).Shows that eyeless can direct ectopic eye development in Drosophila.

    CAS  PubMed  Google Scholar 

  28. Shen, W. & Mardon, G. Ectopic eye development in Drosophila induced by directed dachshund expression. Development 124, 45–52 (1997).

    CAS  PubMed  Google Scholar 

  29. Lewis, E. B. The 1991 Albert Lasker Medical Awards. Clusters of master control genes regulate the development of higher organisms. J. Am. Med. Assoc. 267, 1524–1531 (1992).

    CAS  Google Scholar 

  30. Chow, R. L., Altmann, C. R., Lang, R. A. & Hemmati-Brivanlou, A. Pax6 induces ectopic eyes in a vertebrate. Development 126, 4213–4222 (1999).Shows that ectopic eye development can also occur in vertebrates as a result of ectopic Pax6 expression.

    CAS  PubMed  Google Scholar 

  31. Lagutin, O. et al. Six3 promotes the formation of ectopic optic vesicle-like structures in mouse embryos. Dev. Dyn. 221, 342–349 (2001).

    CAS  PubMed  Google Scholar 

  32. Oliver, G., Loosli, F., Koster, R., Wittbrodt, J. & Gruss, P. Ectopic lens induction in fish in response to the murine homeobox gene Six3. Mech. Dev. 60, 233–239 (1996).

    CAS  PubMed  Google Scholar 

  33. Jordan, T. et al. The human PAX6 gene is mutated in two patients with aniridia. Nature Genet. 1, 328–332 (1992).

    CAS  PubMed  Google Scholar 

  34. Hanson, I. M. et al. PAX6 mutations in aniridia. Hum. Mol. Genet. 2, 915–920 (1993).

    CAS  PubMed  Google Scholar 

  35. Gallardo, M. E. et al. Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies. Genomics 61, 82–91 (1999).

    CAS  PubMed  Google Scholar 

  36. Ton, C. C. et al. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell 67, 1059–1074 (1991).

    CAS  PubMed  Google Scholar 

  37. Ransom, R. The time of action of three mutations affecting Drosophila eye morphogenesis. J. Embryol. Exp. Morphol. 53, 225–235 (1979).

    CAS  PubMed  Google Scholar 

  38. Kumar, J. P. & Moses, K. Expression of evolutionarily conserved eye specification genes during Drosophila embryogenesis. Dev. Genes Evol. 211, 406–414 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Granadino, B. et al. Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene. Genomics 55, 100–105 (1999).

    CAS  PubMed  Google Scholar 

  40. Leppert, G. S., Yang, J. M. & Sundin, O. H. Sequence and location of SIX3, a homeobox gene expressed in the human eye. Ophthalmic Genet. 20, 7–21 (1999).

    CAS  PubMed  Google Scholar 

  41. Noveen, A., Daniel, A. & Hartenstein, V. Early development of the Drosophila mushroom body: the roles of eyeless and dachshund. Development 127, 3475–3488 (2000).

    CAS  PubMed  Google Scholar 

  42. Martini, S. R., Roman, G., Meuser, S., Mardon, G. & Davis, R. L. The retinal determination gene, dachshund, is required for mushroom body cell differentiation. Development 127, 2663–2672 (2000).

    CAS  PubMed  Google Scholar 

  43. Grindley, J. C., Davidson, D. R. & Hill, R. E. The role of Pax-6 in eye and nasal development. Development 121, 1433–1442 (1995).

    CAS  PubMed  Google Scholar 

  44. Boube, M., Benassayag, C., Seroude, L. & Cribbs, D. L. Ras1-mediated modulation of Drosophila homeotic function in cell and segment identity. Genetics 146, 619–628 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Biggs, W. H. et al. The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal trandsuction pathway. EMBO J. 13, 1628–1635 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Brunner, D. et al. A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways. Cell 76, 875–888 (1994).

    CAS  PubMed  Google Scholar 

  47. Marshall, C. J. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr. Opin. Genet. Dev. 4, 82–89 (1994).

    CAS  PubMed  Google Scholar 

  48. Rebay, I. et al. A genetic screen for novel components of the Ras/Mitogen-activated protein kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein. Genetics 154, 695–712 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Nobes, C. D. & Hall, A. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J. Cell Biol. 144, 1235–1244 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Cho, K. O. & Choi, K. W. Fringe is essential for mirror symmetry and morphogenesis in the Drosophila eye. Nature 396, 272–276 (1998).

    CAS  PubMed  Google Scholar 

  51. Dominguez, M. & de Celis, J. F. A dorsal/ventral boundary established by Notch controls growth and polarity in the Drosophila eye. Nature 396, 276–278 (1998).

    CAS  PubMed  Google Scholar 

  52. Cagan, R. L. & Ready, D. F. Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev. 3, 1099–1112 (1989).Shows that Notch functions at many stages in Drosophila eye development and indicates a 'permissive' role for its function.

    CAS  PubMed  Google Scholar 

  53. Younossi-Hartenstein, A., Nassif, C., Green, P. & Hartenstein, V. Early neurogenesis of the Drosophila brain. J. Comp. Neurol. 370, 313–329 (1996).

    CAS  PubMed  Google Scholar 

  54. Postlethwait, J. H. & Schneiderman, H. A. A clonal analysis of development in Drosophila melanogaster: morphogenesis, determination and growth in the wild type antenna. Dev. Biol. 24, 477–519 (1971).

    CAS  PubMed  Google Scholar 

  55. Jones, N. A., Kuo, Y. M., Sun, Y. H. & Beckendorf, S. K. The Drosophila Pax gene eye gone is required for embryonic salivary duct development. Development 125, 4163–4174 (1998).

    CAS  PubMed  Google Scholar 

  56. Baonza, A., Roch, F. & Martin-Blanco, E. DER signaling restricts the boundaries of the wing field during Drosophila development. Proc. Natl Acad. Sci. USA 97, 7331–7335 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Salvini-Plawen, L. V. & Mayr, E. On the evolution of photoreceptors and eyes. Evol. Biol. 10, 207–263 (1977).Seminal paper that provides the most comprehensive argument for a polyphyletic origin of the eye.

    Google Scholar 

  58. Nilsson, D. E. & Pelger, S. A pessimistic estimate of the time required for an eye to evolve. Proc. R. Soc. Lond. B 256, 53–58 (1994).

    CAS  Google Scholar 

  59. Land, M. F. & Fernald, R. D. The evolution of eyes. Annu. Rev. Neurosci. 15, 1–29 (1992).A comprehensive review of the different optical properties of the existing eye types.

    CAS  PubMed  Google Scholar 

  60. Fernald, R. D. The evolution of eyes. Brain Behav. Evol. 50, 253–259 (1997).

    CAS  PubMed  Google Scholar 

  61. Fernald, R. D. Evolution of eyes. Curr. Opin. Neurobiol. 10, 444–450 (2000).

    CAS  PubMed  Google Scholar 

  62. Borod, E. R. & Heberlein, U. Mutual regulation of decapentaplegic and hedgehog during the initiation of differentiation in the Drosophila retina. Dev. Biol. 197, 187–197 (1998).Shows that Hedgehog is required for the initiation of pattern formation in the Drosophila retina.

    CAS  PubMed  Google Scholar 

  63. Burke, R. & Basler, K. Hedgehog dependent patterning in the Drosophila eye can occur in the absence of dpp signaling. Dev. Biol. 179, 360–368 (1996).

    CAS  PubMed  Google Scholar 

  64. Dominguez, M. & Hafen, E. Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosophila eye. Genes Dev. 11, 3254–3264 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Greenwood, S. & Struhl, G. Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway. Development 126, 5795–5808 (1999).

    CAS  PubMed  Google Scholar 

  66. Heberlein, U., Singh, C. M., Luk, A. Y. & Donohoe, T. J. Growth and differentiation in the Drosophila eye coordinated by hedgehog. Nature 373, 709–711 (1995).

    CAS  PubMed  Google Scholar 

  67. Heberlein, U., Wolff, T. & Rubin, G. M. The TGFb homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell 75, 913–926 (1993).

    CAS  PubMed  Google Scholar 

  68. 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 75, 927–938 (1993).

    CAS  PubMed  Google Scholar 

  69. Ready, D. F., Hanson, T. E. & Benzer, S. Development of the Drosophila retina, a neurocrystalline lattice. Dev. Biol. 53, 217–240 (1976).Seminal paper describing the development of the fly compound eye.

    CAS  PubMed  Google Scholar 

  70. Heberlein, U. & Moses, K. Mechanisms of Drosophila retinal morphogenesis: the virtues of being progressive. Cell 81, 987–990 (1995).

    CAS  PubMed  Google Scholar 

  71. Tomlinson, A. & Ready, D. F. Neuronal differentiation in the Drosophila ommatidium. Dev. Biol. 120, 366–376 (1987).

    CAS  PubMed  Google Scholar 

  72. Jarman, A. P., Grell, E. H., Ackerman, L., Jan, L. Y. & Jan, Y. N. atonal is the proneural gene for Drosophila photoreceptors. Nature 369, 398–400 (1994).

    CAS  PubMed  Google Scholar 

  73. Dominguez, M. Dual role for hedgehog in the regulation of the proneural gene atonal during ommatidial development. Development 126, 2345–2353 (1999).

    CAS  PubMed  Google Scholar 

  74. Baker, N. E., Yu, S. & Han, D. Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye. Curr. Biol. 6, 1290–1301 (1996).

    CAS  PubMed  Google Scholar 

  75. Dokucu, M. E., Zipursky, S. L. & Cagan, R. L. Atonal, Rough and the resolution of proneural clusters in the developing Drosophila retina. Development 122, 4139–4147 (1996).

    CAS  PubMed  Google Scholar 

  76. White, N. M. & Jarman, A. P. Drosophila atonal controls photoreceptor R8-specific properties and modulates both receptor tyrosine kinase and hedgehog signaling. Development 127, 1681–1689 (2000).

    CAS  PubMed  Google Scholar 

  77. Jarman, A. P., Sun, Y., Jan, L. Y. & Jan, Y. N. Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs and photoreceptors. Development 121, 2019–2030 (1995).

    CAS  PubMed  Google Scholar 

  78. Brown, N. L. et al. Math5 encodes a murine basic helix–loop–helix transcription factor expressed during early stages of retinal neurogenesis. Development 125, 4821–4833 (1998).

    CAS  PubMed  Google Scholar 

  79. Jensen, A. M. & Wallace, V. A. Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina. Development 124, 363–371 (1997).

    CAS  PubMed  Google Scholar 

  80. Stenkamp, D. L., Frey, R. A., Prabhudesai, S. N. & Raymond, P. A. Function for Hedgehog genes in zebrafish retinal development. Dev. Biol. 220, 238–252 (2000).

    CAS  PubMed  Google Scholar 

  81. Kanekar, S. et al. Xath5 participates in a network of bHLH genes in the developing Xenopus retina. Neuron 19, 981–994 (1997).

    CAS  PubMed  Google Scholar 

  82. Masai, I., Stemple, D. L., Okamoto, H. & Wilson, S. W. Midline signals regulate retinal neurogenesis in zebrafish. Neuron 27, 251–263 (2000).

    CAS  PubMed  Google Scholar 

  83. Levine, E. M., Roelink, H., Turner, J. & Reh, T. A. Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. J. Neurosci. 17, 6277–6288 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Ekker, S. C. et al. Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr. Biol. 5, 944–955 (1995).

    CAS  PubMed  Google Scholar 

  85. Macdonald, R. et al. Midline signalling is required for Pax gene regulation and patterning of the eyes. Development 121, 3267–3278 (1995).

    CAS  PubMed  Google Scholar 

  86. Brown, N. L., Patel, S., Brzezinski, J. & Glaser, T. Math5 is required for retinal ganglion cell and optic nerve formation. Development 128, 2497–2508 (2001).Describes the role that the mouse homologue of atonal has in retinal ganglion cell formation.

    CAS  PubMed  Google Scholar 

  87. Wang, S. W. et al. Requirement for math5 in the development of retinal ganglion cells. Genes Dev. 15, 24–29 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Kay, J. N., Finger-Baier, K. C., Roeser, T., Staub, W. & Baier, H. Retinal ganglion cell genesis requires lakritz, a zebrafish atonal homolog. Neuron 30, 725–736 (2001).Describes the role of the zebrafish homologue of atonal in retinal development.

    CAS  PubMed  Google Scholar 

  89. Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413 (1996).Describes the effects on patterning in hedgehog-mutant mice.

    CAS  PubMed  Google Scholar 

  90. Belloni, E. et al. Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly. Nature Genet. 14, 353–356 (1996).

    CAS  PubMed  Google Scholar 

  91. Roessler, E. et al. Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nature Genet. 14, 357–360 (1996).

    CAS  PubMed  Google Scholar 

  92. Ming, J. E., Roessler, E. & Muenke, M. Human developmental disorders and the Sonic hedgehog pathway. Mol. Med. Today 4, 343–349 (1998).

    CAS  PubMed  Google Scholar 

  93. Nasevicius, A. & Ekker, S. C. Effective targeted gene 'knockdown' in zebrafish. Nature Genet. 26, 216–220 (2000).

    CAS  PubMed  Google Scholar 

  94. Ready, D. F. A multifaceted approach to neural development. Trends Neurosci. 12, 102–110 (1989).

    CAS  PubMed  Google Scholar 

  95. Tomlinson, A. The cellular dynamics of pattern formation in the eye of Drosophila. J. Embryol. Exp. Morphol. 89, 313–331 (1985).

    CAS  PubMed  Google Scholar 

  96. Tomlinson, A. Cellular interactions in the developing Drosophila eye. Development 104, 183–193 (1988).

    CAS  PubMed  Google Scholar 

  97. Tio, M., Ma, C. & Moses, K. spitz, a Drosophila homolog of transforming growth factor-α, is required in the founding photoreceptor cells of the compound eye facets. Mech. Dev. 48, 13–23 (1994).

    CAS  PubMed  Google Scholar 

  98. Tio, M. & Moses, K. The Drosophila TGFα homolog Spitz acts in photoreceptor recruitment in the developing retina. Development 124, 343–351 (1997).

    CAS  PubMed  Google Scholar 

  99. Kumar, J. P. et al. Dissecting the roles of the Drosophila EGF receptor in eye development and MAP kinase activation. Development 125, 3875–3885 (1998).

    CAS  PubMed  Google Scholar 

  100. Freeman, M. The spitz gene is required for photoreceptor determination in the Drosophila eye where it interacts with the EGF receptor. Mech. Dev. 48, 25–33 (1994).

    CAS  PubMed  Google Scholar 

  101. Freeman, M. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell 87, 651–660 (1996).

    CAS  PubMed  Google Scholar 

  102. Freeman, M. Cell determination strategies in the Drosophila eye. Development 124, 261–270 (1997).

    CAS  PubMed  Google Scholar 

  103. Wolff, T. & Ready, D. F. in The Development of Drosophila melanogaster (eds Bate, M. & Martinez Arias, A.) 1277–1326 (Cold Spring Harbor Laboratory Press, New York, 1993).

    Google Scholar 

  104. Bailey, C. H. & Gouras, P. in Principles of Neural Science, 2nd edn (eds Kandel, E. R. & Schwartz, J. H.) 344–355 (McGraw–Hill, New York, 1985).

    Google Scholar 

  105. Hadorn, E. Transdetermination in cells. Sci. Am. 219, 110–172 (1968).

    CAS  PubMed  Google Scholar 

  106. Hadorn, E. in The Genetics and Biology of Drosphila, Vol. 2c (eds Ashburner, M. & Wright) 555–617 (Academic, New York, 1978).

    Google Scholar 

  107. Hill, R. E. et al. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354, 522–525 (1991).

    CAS  PubMed  Google Scholar 

  108. Oliver, G. et al. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045–4055 (1995).

    CAS  PubMed  Google Scholar 

  109. Jean, D., Bernier, G. & Gruss, P. Six6 (Optx2) is a novel murine Six3-related homeobox gene that demarcates the presumptive pituitary/hypothalamic axis and the ventral optic stalk. Mech. Dev. 84, 31–40 (1999).

    CAS  PubMed  Google Scholar 

  110. Xu, P. X., Woo, I., Her, H., Beier, D. R. & Maas, R. L. Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode. Development 124, 219–231 (1997).

    CAS  PubMed  Google Scholar 

  111. Borsani, G. et al. EYA4, a novel vertebrate gene related to Drosophila eyes absent. Hum. Mol. Genet. 8, 11–23 (1999).

    CAS  PubMed  Google Scholar 

  112. Davis, R. J., Shen, W., Heanue, T. A. & Mardon, G. Mouse Dach, a homologue of Drosophila dachshund, is expressed in the developing retina, brain and limbs. Dev. Genes Evol. 209, 526–536 (1999).

    CAS  PubMed  Google Scholar 

  113. Davis, R. J., Shen, W., Sandler, Y. I., Heanue, T. A. & Mardon, G. Characterization of mouse Dach2, a homologue of Drosophila dachshund. Mech. Dev. 102, 169–179 (2001).

    CAS  PubMed  Google Scholar 

  114. Lee, J. J., Von Kessler, D., Parks, S. & Beachy, P. A. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell 71, 33–50 (1992).

    CAS  PubMed  Google Scholar 

  115. Echelard, Y. et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75, 1417–1430 (1993).

    CAS  PubMed  Google Scholar 

  116. 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 73, 1307–1321 (1993).

    CAS  PubMed  Google Scholar 

  117. Livneh, E., Glazer, L., Segal, D., Schlessinger, J. & Shilo, B. Z. The Drosophila EGF receptor gene homolog: conservation of both hormone binding and kinase domains. Cell 40, 599–607 (1985).

    CAS  PubMed  Google Scholar 

  118. Baker, N. E. & Rubin, G. M. Effect on eye development of dominant mutations in Drosophila homologue of the EGF receptor. Nature 340, 150–153 (1989).

    CAS  PubMed  Google Scholar 

  119. Reneker, L. W., Silversides, D. W., Patel, K. & Overbeek, P. A. TGFα can act as a chemoattractant to perioptic mesenchymal cells in developing mouse eyes. Development 121, 1669–1680 (1995).

    CAS  PubMed  Google Scholar 

  120. Luetteke, N. C. et al. The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev. 8, 399–413 (1994).

    CAS  PubMed  Google Scholar 

  121. 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 43, 567–581 (1985).

    CAS  PubMed  Google Scholar 

  122. Lindsell, C. E., Boulter, J., diSibio, G., Gossler, A. & Weinmaster, G. Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand–receptor pairs that may function in neural development. Mol. Cell. Neurosci. 8, 14–27 (1996).

    CAS  PubMed  Google Scholar 

  123. McCright, B. et al. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128, 491–502 (2001).

    CAS  PubMed  Google Scholar 

  124. Uyttendaele, H. et al. Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene. Development 122, 2251–2259 (1996).

    CAS  PubMed  Google Scholar 

  125. Hoffmann, F. M. & Goodman, W. Identification in transgenic animals of the Drosophila decapentaplegic sequences required for embryonic dorsal pattern formation. Genes Dev. 1, 615–625 (1987).

    CAS  PubMed  Google Scholar 

  126. 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-β family in Drosophila. Development 111, 657–665 (1991).

    CAS  PubMed  Google Scholar 

  127. Furuta, Y. & Hogan, B. L. BMP4 is essential for lens induction in the mouse embryo. Genes Dev. 12, 3764–3775 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Wawersik, S. et al. BMP7 acts in murine lens placode development. Dev. Biol. 207, 176–188 (1999).

    CAS  PubMed  Google Scholar 

  129. Dudley, A. T. & Robertson, E. J. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev. Dyn. 208, 349–362 (1997).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Emory University School of Medicine, 1648 Pierce Drive, Atlanta, 30033, Georgia, USA

    Justin P. Kumar

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  1. Justin P. Kumar
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DATABASES

LocusLink 

ANTC

ath5

ato

Btl

BXC

dac

Dl

dpp

Egfr

E(Spl)C

exd

ey

eya

eyg

Grk

hh

hth

Htl

Mam

Math5

Notch

optix

Pax2

Pax6

pb

Pnt

rl

RTK

Ser

shh

SIX3

so

Spitz

Su(H)

toy

tsh

twhh

Ubx

Vn

yan 

OMIM 

aniridia

LINKS

RTK

Glossary

MUSHROOM BODY

The brain region of insects that might be implicated in complex types of behaviour, such as learning, social behaviour and spatial memory.

NON AUTONOMOUS

A cell non-autonomous trait is one in which genotypically mutant cells cause other cells (regardless of their genotype) to show a mutant phenotype.

CLONAL ANALYSIS

(also known as mosaic analysis). The process of following the progenitors derived from a single cell (a clone). Clonal analysis can be used to infer how many cells make up an anlage, when gene action takes place, and if lineage has a role in cell-fate determination.

HOX GENE

One of a group of linked regulatory genes involved in patterning the animal body axis during development.

NOTUM

The dorsal or upper surface of any insect thoracic segment.

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Kumar, J. Signalling pathways in Drosophila and vertebrate retinal development. Nat Rev Genet 2, 846–857 (2001). https://doi.org/10.1038/35098564

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