Fast and Furious 800. The Retinal Determination Gene Network in Drosophila



The Drosophila compound eye is formed by about 800 ommatidia or simple eyes, packed in an almost crystalline lattice. The precise ommatidial arrangement makes the fly eye especially sensitive to pattern aberrations. These properties, together with the fact that the eye is an external and largely dispensable organ, have made the Drosophila eye an excellent genetic model to investigate the mechanisms of cell proliferation, patterning and differentiation, as well as mechanisms of human disease, such as cancer, neurodegeneration or metabolic pathologies. Part of these studies have coalesced into the Drosophila eye (or retinal) gene regulatory network (GRN): a text-book example of an organ-specification gene network that has been used as a point-of-comparison in the study of the mechanisms of eye specification and evolution, as well as a paradigm of signaling integration. This paper reviews the gene network that covers the period from eye progenitor specification to the onset of retinal differentiation as marked by activation of the proneural gene atonal, while paying special attention to the dynamics of the network and its intimate relation to the control of eye size.


Eye disc Compound eye Visual systems Drosophila development Gene networks Organ growth Cell specification Organ size 



Recent work in the Casares lab related to the subject of this review has been partly funded through grants BFU2009-07044 and BFU2012-34324 from the Spanish Ministry of Science and Innovation/MINECO. We specially thank S. Aerts (KU, Leuven), M. Friedrich (Wayne State Univ., Detroit), F. Pichaud (UCL, London) and F. Pignoni (Upstate Medical Univ., Syracuse) for their critical comments. IA has been supported through “Programa de Fortalecimiento” of Pablo de Olavide University and a MSC postdoctoral contract from the EU H2020 Program.


  1. Aerts, S., Quan, X. J., Claeys, A., Naval Sanchez, M., Tate, P., Yan, J., et al. (2010). Robust target gene discovery through transcriptome perturbations and genome-wide enhancer predictions in Drosophila uncovers a regulatory basis for sensory specification. PLoS Biology, 8(7), e1000435.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Anderson, A. M., Weasner, B. M., Weasner, B. P., & Kumar, J. P. (2012). Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development. Development, 139(5), 991–1000.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Arendt, D., Tessmar, K., de Campos-Baptista, M. I., Dorresteijn, A., & Wittbrodt, J. (2002). Development of pigment-cup eyes in the polychaete Platynereis dumerilii and evolutionary conservation of larval eyes in Bilateria. Development, 129(5), 1143–1154.PubMedGoogle Scholar
  4. Atkins, M., Jiang, Y., Sansores-Garcia, L., Jusiak, B., Halder, G., & Mardon, G. (2013). Dynamic rewiring of the Drosophila retinal determination network switches its function from selector to differentiation. PLoS Genet, 9, e1003731.Google Scholar
  5. Azevedo, R. B., French, V., & Partridge, L. (2002). Temperature modulates epidermal cell size in Drosophila melanogaster. Journal of Insect Physiology, 48(2), 231–237.PubMedCrossRefGoogle Scholar
  6. Bach, E. A., Ekas, L. A., Ayala-Camargo, A., Flaherty, M. S., Lee, H., Perrimon, N., & Baeg, G. H. (2007). GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. Gene Expr Patterns, 7, 323–331.Google Scholar
  7. Bach, E. A., Vincent, S., Zeidler, M. P., & Perrimon, N. (2003). A sensitized genetic screen to identify novel regulators and components of the Drosophila janus kinase/signal transducer and activator of transcription pathway. Genetics, 165, 1149–1166.Google Scholar
  8. Baker, N. E. (1988). Transcription of the segment-polarity gene wingless in the imaginal discs of Drosophila, and the phenotype of a pupal-lethal wg mutation. Development, 102(3), 489–497.PubMedGoogle Scholar
  9. Baker, N. E. (2001). Cell proliferation, survival, and death in the Drosophila eye. Seminars in Cell & Developmental Biology, 12(6), 499–507.CrossRefGoogle Scholar
  10. Baker, N. E., Bhattacharya, A., & Firth, L. C. (2009). Regulation of Hh signal transduction as Drosophila eye differentiation progresses. Development Biology, 335(2), 356–366.CrossRefGoogle Scholar
  11. Baonza, A., & Freeman, M. (2001). Notch signalling and the initiation of neural development in the Drosophila eye. Development, 128(20), 3889–3898.PubMedGoogle Scholar
  12. Benlali, A., Draskovic, I., Hazelett, D. J., & Treisman, J. E. (2000). act up controls actin polymerization to alter cell shape and restrict Hedgehog signaling in the Drosophila eye disc. Cell, 101(3), 271–281.PubMedCrossRefGoogle Scholar
  13. Bessa, J., Carmona, L., & Casares, F. (2009). Zinc-finger paralogues tsh and tio are functionally equivalent during imaginal development in Drosophila and maintain their expression levels through auto- and cross-negative feedback loops. Developmental Dynamics, 238(1), 19–28.PubMedCrossRefGoogle Scholar
  14. Bessa, J., & Casares, F. (2005). Restricted teashirt expression confers eye-specific responsiveness to Dpp and Wg signals during eye specification in Drosophila. Development, 132(22), 5011–5020.PubMedCrossRefGoogle Scholar
  15. Bessa, J., Gebelein, B., Pichaud, F., Casares, F., & Mann, R. S. (2002). Combinatorial control of Drosophila eye development by eyeless, homothorax, and teashirt. Genes & Development, 16(18), 2415–2427.CrossRefGoogle Scholar
  16. Bhattacharya, A., & Baker, N. E. (2011). A network of broadly expressed HLH genes regulates tissue-specific cell fates. Cell, 147(4), 881–892.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Blackman, R. K., Sanicola, M., Raftery, L. A., Gillevet, T., & Gelbart, W. M. (1991). An extensive 3′ cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-beta family in Drosophila. Development, 111(3), 657–666.PubMedGoogle Scholar
  18. Bonini, N. M., Bui, Q. T., Gray-Board, G. L., & Warrick, J. M. (1997). The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development, 124(23), 4819–4826.PubMedGoogle Scholar
  19. Bonini, N. M., Leiserson, W. M., & Benzer, S. (1993). The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell, 72, 379–395.Google Scholar
  20. Borod, E. R., & Heberlein, U. (1998). Mutual regulation of decapentaplegic and hedgehog during the initiation of differentiation in the Drosophila retina. Development Biology, 197(2), 187–197.CrossRefGoogle Scholar
  21. Braid, L. R., & Verheyen, E. M. (2008). Drosophila nemo promotes eye specification directed by the retinal determination gene network. Genetics, 180(1), 283–299.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Bras-Pereira, C., Bessa, J., & Casares, F. (2006). Odd-skipped genes specify the signaling center that triggers retinogenesis in Drosophila. Development, 133(21), 4145–4149.PubMedCrossRefGoogle Scholar
  23. Bras-Pereira, C., Casares, F., & Janody, F. (2015). The retinal determination gene Dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex. Development, 142(8), 1470–1479.PubMedCrossRefGoogle Scholar
  24. Brennan, C. A., Ashburner, M., & Moses, K. (1998). Ecdysone pathway is required for furrow progression in the developing Drosophila eye. Development, 125(14), 2653–2664.PubMedGoogle Scholar
  25. Brennan, C. A., Li, T. R., Bender, M., Hsiung, F., & Moses, K. (2001). Broad-complex, but not ecdysone receptor, is required for progression of the morphogenetic furrow in the Drosophila eye. Development, 128(1), 1–11.PubMedGoogle Scholar
  26. Brown, N. L., Sattler, C. A., Paddock, S. W., & Carroll, S. B. (1995). Hairy and emc negatively regulate morphogenetic furrow progression in the Drosophila eye. Cell, 80, 879–887.Google Scholar
  27. Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013). Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature Methods, 10(12), 1213–1218.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Bui, Q. T., Zimmerman, J. E., Liu, H., Gray-Board, G. L., & Bonini, N. M. (2000). Functional analysis of an eye enhancer of the Drosophila eyes absent gene: Differential regulation by eye specification genes. Development Biology, 221(2), 355–364.CrossRefGoogle Scholar
  29. Callaerts, P., Halder, G., & Gehring, W. J. (1997). PAX-6 in development and evolution. Annual Review of Neuroscience, 20, 483–532.PubMedCrossRefGoogle Scholar
  30. Cavodeassi, F., Diez Del Corral, R., Campuzano, S., & Dominguez, M. (1999). Compartments and organising boundaries in the Drosophila eye: the role of the homeodomain Iroquois proteins. Development, 126, 4933–4942.Google Scholar
  31. Chang, T., Mazotta, J., Dumstrei, K., Dumitrescu, A., & Hartenstein, V. (2001). Dpp and Hh signaling in the Drosophila embryonic eye field. Development, 128(23), 4691–4704.PubMedGoogle Scholar
  32. Chanut, F., & Heberlein, U. (1997). Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina. Development, 124(2), 559–567.PubMedGoogle Scholar
  33. Chao, J. L., Tsai, Y. C., Chiu, S. J., & Sun, Y. H. (2004). Localized Notch signal acts through eyg and upd to promote global growth in Drosophila eye. Development, 131, 3839–3847.Google Scholar
  34. Charlton-Perkins, M., & Cook, T. A. (2010). Building a fly eye: Terminal differentiation events of the retina, corneal lens, and pigmented epithelia. Current Topics in Developmental Biology, 93, 129–173.PubMedCrossRefGoogle Scholar
  35. Chen, R., Amoui, M., Zhang, Z., & Mardon, G. (1997). Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell, 91(7), 893–903.PubMedCrossRefGoogle Scholar
  36. Cheyette, B. N., Green, P. J., Martin, K., Garren, H., Hartenstein, V., & Zipursky, S. L. (1994). The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron, 12(5), 977–996.PubMedCrossRefGoogle Scholar
  37. Cho, K. O., & Choi, K. W. (1998). Fringe is essential for mirror symmetry and morphogenesis in the Drosophila eye. Nature, 396, 272–276.Google Scholar
  38. Clements, J., Hens, K., Merugu, S., Dichtl, B., de Couet, H. G., & Callaerts, P. (2009). Mutational analysis of the eyeless gene and phenotypic rescue reveal that an intact Eyeless protein is necessary for normal eye and brain development in Drosophila. Development Biology, 334(2), 503–512.CrossRefGoogle Scholar
  39. Cohen, S. M., & Jurgens, G. (1990). Mediation of Drosophila head development by gap-like segmentation genes. Nature, 346(6283), 482–485.PubMedCrossRefGoogle Scholar
  40. Corrigall, D., Walther, R. F., Rodriguez, L., Fichelson, P., & Pichaud, F. (2007). Hedgehog signaling is a principal inducer of Myosin-II-driven cell ingression in Drosophila epithelia. Developmental Cell, 13(5), 730–742.PubMedCrossRefGoogle Scholar
  41. Czerny, T., Halder, G., Kloter, U., Souabni, A., Gehring, W. J., & Busslinger, M. (1999). twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Molecular Cell, 3(3), 297–307.PubMedCrossRefGoogle Scholar
  42. Daniel, A., Dumstrei, K., Lengyel, J. A., & Hartenstein, V. (1999). The control of cell fate in the embryonic visual system by atonal, tailless and EGFR signaling. Development, 126(13), 2945–2954.PubMedGoogle Scholar
  43. Datta, R. R., Lurye, J. M., & Kumar, J. P. (2009). Restriction of ectopic eye formation by Drosophila teashirt and tiptop to the developing antenna. Developmental Dynamics.Google Scholar
  44. Davie, K., Jacobs, J., Atkins, M., Potier, D., Christiaens, V., & Halder, G. (2015). Discovery of transcription factors and regulatory regions driving in vivo tumor development by ATAC-seq and FAIRE-seq open chromatin profiling. PLoS Genetics, 11(2), e1004994.PubMedPubMedCentralCrossRefGoogle Scholar
  45. de Nooij, J. C., Letendre, M. A., & Hariharan, I. K. (1996). A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell, 87(7), 1237–1247.PubMedCrossRefGoogle Scholar
  46. Dominguez-Cejudo, M. A., & Casares, F. (2015). Anteroposterior patterning of Drosophila ocelli requires an anti-repressor mechanism within the hh pathway mediated by the Six3 gene Optix. Development, 142(16), 2801–2809.PubMedCrossRefGoogle Scholar
  47. Dominguez, M., & de Celis, J. F. (1998). A dorsal/ventral boundary established by Notch controls growth and polarity in the Drosophila eye. Nature, 396, 276–278.Google Scholar
  48. Dominguez, M., Ferres-Marco, D., Gutierrez-Avino, F. J., Speicher, S. A., & Beneyto, M. (2004). Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster. Nat Genet, 36, 31–39.Google Scholar
  49. Duman-Scheel, M., Weng, L., Xin, S., & Du, W. (2002). Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature, 417(6886), 299–304.PubMedCrossRefGoogle Scholar
  50. Ekas, L. A., Baeg, G. H., Flaherty, M. S., Ayala-Camargo, A., & Bach, E. A. (2006). JAK/STAT signaling promotes regional specification by negatively regulating wingless expression in Drosophila. Development, 133, 4721–4729.Google Scholar
  51. Escudero, L. M., Bischoff, M., & Freeman, M. (2007). Myosin II regulates complex cellular arrangement and epithelial architecture in Drosophila. Developmental Cell, 13(5), 717–729.PubMedCrossRefGoogle Scholar
  52. Escudero, L. M., & Freeman, M. (2007). Mechanism of G1 arrest in the Drosophila eye imaginal disc. BMC Developmental Biology, 7, 13.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Fasano, L., Roder, L., Core, N., Alexandre, E., Vola, C., Jacq, B., et al. (1991). The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs. Cell, 64(1), 63–79.PubMedCrossRefGoogle Scholar
  54. Fernald, R. D. (2000). Evolution of eyes. Current Opinion in Neurobiology, 10(4), 444–450.PubMedCrossRefGoogle Scholar
  55. Finkelstein, R., & Perrimon, N. (1990). The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila head development. Nature, 346(6283), 485–488.PubMedCrossRefGoogle Scholar
  56. Finkelstein, R., Smouse, D., Capaci, T. M., Spradling, A. C., & Perrimon, N. (1990). The orthodenticle gene encodes a novel homeo domain protein involved in the development of the Drosophila nervous system and ocellar visual structures. Genes & Development, 4(9), 1516–1527.CrossRefGoogle Scholar
  57. Firth, L. C., & Baker, N. E. (2005). Extracellular signals responsible for spatially regulated proliferation in the differentiating Drosophila eye. Developmental Cell, 8(4), 541–551.PubMedCrossRefGoogle Scholar
  58. Firth, L. C., & Baker, N. E. (2009). Retinal determination genes as targets and possible effectors of extracellular signals. Dev Biol, 327, 366–375.Google Scholar
  59. Flaherty, M. S., Salis, P., Evans, C. J., Ekas, L. A., Marouf, A., Zavadil, J., Banerjee, U., & Bach, E. A. (2010). chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila. Dev Cell, 18, 556–568.Google Scholar
  60. Flaherty, M. S., Zavadil, J., Ekas, L. A., & Bach, E. A. (2009). Genome-wide expression profiling in the Drosophila eye reveals unexpected repression of notch signaling by the JAK/STAT pathway. Dev Dyn, 238, 2235–2253.Google Scholar
  61. Friedrich, M., & Benzer, S. (2000). Divergent decapentaplegic expression patterns in compound eye development and the evolution of insect metamorphosis. Journal of Experimental Zoology, 288(1), 39–55.PubMedCrossRefGoogle Scholar
  62. Fu, W., & Baker, N. E. (2003). Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development. Development, 130(21), 5229–5239.PubMedCrossRefGoogle Scholar
  63. Garcia-Ojalvo, J., & Martinez Arias, A. (2012). Towards a statistical mechanics of cell fate decisions. Current Opinion in Genetics & Development, 22(6), 619–626.CrossRefGoogle Scholar
  64. Gehring, W., & Seimiya, M. (2010). Eye evolution and the origin of Darwin’s eye prototype. Italian Journal of Zoology, 77(2), 124–136.CrossRefGoogle Scholar
  65. Gehring, W. J. (1996). The master control gene for morphogenesis and evolution of the eye. Genes to Cells, 1(1), 11–15.PubMedCrossRefGoogle Scholar
  66. Giresi, P. G., Kim, J., McDaniell, R. M., Iyer, V. R., & Lieb, J. D. (2007). FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin. Genome Research, 17(6), 877–885.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Green, P., Hartenstein, A. Y., & Hartenstein, V. (1993). The embryonic development of the Drosophila visual system. Cell and Tissue Research, 273(3), 583–598.PubMedCrossRefGoogle Scholar
  68. Greenwood, S., & Struhl, G. (1999). ‘Progression of the morphogenetic furrow in the Drosophila eye: The roles of Hedgehog, Decapentaplegic and the Raf pathway. Development, 126(24), 5795–5808.PubMedGoogle Scholar
  69. Guantes, R., & Poyatos, J. F. (2008). Multistable decision switches for flexible control of epigenetic differentiation. PLoS Computational Biology, 4(11), e1000235.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Gutierrez-Avino, F. J., Ferres-Marco, D., & Dominguez, M. (2009). The position and function of the Notch-mediated eye growth organizer: the roles of JAK/STAT and four-jointed. EMBO Rep, 10, 1051–1058.Google Scholar
  71. Halder, G., Callaerts, P., & Gehring, W. J. (1995). Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science, 267(5205), 1788–1792.PubMedCrossRefGoogle Scholar
  72. Hammerle, B., & Ferrus, A. (2003). Expression of enhancers is altered in Drosophila melanogaster hybrids. Evol Dev, 5(3), 221–230.PubMedCrossRefGoogle Scholar
  73. Hauck, B., Gehring, W. J., & Walldorf, U. (1999). Functional analysis of an eye specific enhancer of the eyeless gene in Drosophila. Proc Natl Acad Sci U S A, 96(2), 564–569.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Haynie, J. L., & Bryant, P. J. (1986). Development of the eye-antenna imaginal disc and morphogenesis of the adult head in Drosophila melanogaster. Journal of Experimental Zoology, 237(3), 293–308.PubMedCrossRefGoogle Scholar
  75. Hazelett, D. J., Bourouis, M., Walldorf, U., & Treisman, J. E. (1998). 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.Google Scholar
  76. Heberlein, U., Borod, E. R., & Chanut, F. A. (1998). Dorsoventral patterning in the Drosophila retina by wingless. Development, 125, 567–577.Google Scholar
  77. Heberlein, U., Wolff, T., & Rubin, G. M. (1993). The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell, 75(5), 913–926.PubMedCrossRefGoogle Scholar
  78. Herboso, L., Oliveira, M. M., Talamillo, A., Perez, C., Gonzalez, M., Martin, D. et al. (2015) Ecdysone promotes growth of imaginal discs through the regulation of Thor in D. melanogaster. Scientific Reports, 5, 12383.Google Scholar
  79. Hoge, M. A. (1915). Another gene in the fourth chromosome of Drosophila. The American Naturalist, 49, 47–49.CrossRefGoogle Scholar
  80. Horsfield, J., Penton, A., Secombe, J., Hoffman, F. M., & Richardson, H. (1998). decapentaplegic is required for arrest in G1 phase during Drosophila eye development. Development, 125(24), 5069–5078.PubMedGoogle Scholar
  81. Huang, J., Wu, S., Barrera, J., Matthews, K., & Pan, D. (2005). The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell, 122(3), 421–434.PubMedCrossRefGoogle Scholar
  82. Jang, C. C., Chao, J. L., Jones, N., Yao, L. C., Bessarab, D. A., Kuo, Y. M., Jun, S., Desplan, C., Beckendorf, S. K., & Sun, Y. H. (2003). Two Pax genes, eye gone and eyeless, act cooperatively in promoting Drosophila eye development. Development, 130, 2939–2951.Google Scholar
  83. Janody, F., Lee, J. D., Jahren, N., Hazelett, D. J., Benlali, A., Miura, G. I., et al. (2004). A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development. Genetics, 166(1), 187–200.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Jarman, A. P., Sun, Y., Jan, L. Y., & Jan, Y. N. (1995). Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs and photoreceptors. Development, 121(7), 2019–2030.PubMedGoogle Scholar
  85. Karandikar, U. C., Jin, M., Jusiak, B., Kwak, S., Chen, R., & Mardon, G. (2014). Drosophila eyes absent is required for normal cone and pigment cell development. PLoS ONE, 9(7), e102143.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Kenyon, K. L., Li, D. J., Clouser, C., Tran, S., & Pignoni, F. (2005a). Fly SIX-type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye development. Developmental Dynamics, 234(3), 497–504.PubMedCrossRefGoogle Scholar
  87. Kenyon, K. L., Ranade, S. S., Curtiss, J., Mlodzik, M., & Pignoni, F. (2003). Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head. Developmental Cell, 5(3), 403–414.PubMedCrossRefGoogle Scholar
  88. Kenyon, K. L., Yang-Zhou, D., Cai, C. Q., Tran, S., Clouser, C., Decene, G., et al. (2005b). Partner specificity is essential for proper function of the SIX-type homeodomain proteins Sine oculis and Optix during fly eye development. Development Biology, 286(1), 158–168.CrossRefGoogle Scholar
  89. Kronhamn, J., Frei, E., Daube, M., Jiao, R., Shi, Y., Noll, M., et al. (2002). Headless flies produced by mutations in the paralogous Pax6 genes eyeless and twin of eyeless. Development, 129(4), 1015–1026.PubMedGoogle Scholar
  90. Kumar, J. P., & Moses, K. (2001). The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development. Development, 128(14), 2689–2697.PubMedGoogle Scholar
  91. Lane, M. E., Sauer, K., Wallace, K., Jan, Y. N., Lehner, C. F., & Vaessin, H. (1996). Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Cell, 87(7), 1225–1235.PubMedCrossRefGoogle Scholar
  92. Laugier, E., Yang, Z., Fasano, L., Kerridge, S., & Vola, C. (2005). A critical role of teashirt for patterning the ventral epidermis is masked by ectopic expression of tiptop, a paralog of teashirt in Drosophila. Development Biology, 283(2), 446–458.CrossRefGoogle Scholar
  93. Lee, J. D., & Treisman, J. E. (2001). The role of Wingless signaling in establishing the anteroposterior and dorsoventral axes of the eye disc. Development, 128(9), 1519–1529.PubMedGoogle Scholar
  94. Li, Y., Jiang, Y., Chen, Y., Karandikar, U., Hoffman, K., Chattopadhyay, A., et al. (2013). optix functions as a link between the retinal determination network and the dpp pathway to control morphogenetic furrow progression in Drosophila. Development Biology, 381(1), 50–61.CrossRefGoogle Scholar
  95. Lopes, C. S., & Casares, F. (2010). hth maintains the pool of eye progenitors and its downregulation by Dpp and Hh couples retinal fate acquisition with cell cycle exit. Development Biology, 339(1), 78–88.CrossRefGoogle Scholar
  96. Lopes, C. S., & Casares, F. (2015). Eye selector logic for a coordinated cell cycle exit. PLoS Genetics, 11(2), e1004981.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Lubensky, D. K., Pennington, M. W., Shraiman, B. I., & Baker, N. E. (2011). A dynamical model of ommatidial crystal formation. Proceedings of the National Academy of Sciences, 108(27), 11145–11150.CrossRefGoogle Scholar
  98. Ma, C., & Moses, K. (1995). Wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye. Development, 121(8), 2279–2289.PubMedGoogle Scholar
  99. Ma, C., Zhou, Y., Beachy, P. A., & Moses, K. (1993). The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye. Cell, 75(5), 927–938.PubMedCrossRefGoogle Scholar
  100. Mardon, G., Solomon, N. M., & Rubin, G. M. (1994). dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development, 120(12), 3473–3486.PubMedGoogle Scholar
  101. Martin-Duran, J. M., Monjo, F., & Romero, R. (2012). Morphological and molecular development of the eyes during embryogenesis of the freshwater planarian Schmidtea polychroa. Development Genes and Evolution, 222(1), 45–54.PubMedCrossRefGoogle Scholar
  102. McClure, K. D., & Schubiger, G. (2005). Developmental analysis and squamous morphogenesis of the peripodial epithelium in Drosophila imaginal discs. Development, 132(22), 5033–5042.PubMedCrossRefGoogle Scholar
  103. Michaut, L., Flister, S., Neeb, M., White, K. P., Certa, U., & Gehring, W. J. (2003). Analysis of the eye developmental pathway in Drosophila using DNA microarrays. Proceedings of the National Academy of Sciences, 100(7), 4024–4029.CrossRefGoogle Scholar
  104. Mirth, C. K., & Shingleton, A. W. (2012). Integrating body and organ size in Drosophila: Recent advances and outstanding problems. Front Endocrinol (Lausanne), 3, 49.Google Scholar
  105. Morillo, S. A., Braid, L. R., Verheyen, E. M., & Rebay, I. (2012). Nemo phosphorylates Eyes absent and enhances output from the Eya-Sine oculis transcriptional complex during Drosophila retinal determination. Development Biology, 365(1), 267–276.CrossRefGoogle Scholar
  106. Mozer, B. A., & Easwarachandran, K. (1999). Pattern formation in the absence of cell proliferation: Tissue-specific regulation of cell cycle progression by string (stg) during Drosophila eye development. Development Biology, 213(1), 54–69.CrossRefGoogle Scholar
  107. Nakanishi, N., Camara, A. C., Yuan, D. C., Gold, D. A., & Jacobs, D. K. (2015). Gene Expression Data from the Moon Jelly, Aurelia, Provide Insights into the Evolution of the Combinatorial Code Controlling Animal Sense Organ Development. PLoS ONE, 10(7), e0132544.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Naval-Sanchez, M., Potier, D., Haagen, L., Sanchez, M., Munck, S., Van de Sande, B., et al. (2013). Comparative motif discovery combined with comparative transcriptomics yields accurate targetome and enhancer predictions. Genome Research, 23(1), 74–88.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Netter, S., Fauvarque, M. O., Diez del Corral, R., Dura, J. M., & Coen, D. (1998). white+ transgene insertions presenting a dorsal/ventral pattern define a single cluster of homeobox genes that is silenced by the polycomb-group proteins in Drosophila melanogaster. Genetics, 149, 257–275.Google Scholar
  110. Niimi, T., Seimiya, M., Kloter, U., Flister, S., & Gehring, W. J. (1999). Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila. Development, 126(10), 2253–2260.PubMedGoogle Scholar
  111. Niwa, N., Hiromi, Y., & Okabe, M. (2004). A conserved developmental program for sensory organ formation in Drosophila melanogaster. Nature Genetics, 36(3), 293–297.PubMedCrossRefGoogle Scholar
  112. Ostrin, E. J., Li, Y., Hoffman, K., Liu, J., Wang, K., Zhang, L., et al. (2006). Genome-wide identification of direct targets of the Drosophila retinal determination protein Eyeless. Genome Research, 16(4), 466–476.PubMedCrossRefPubMedCentralGoogle Scholar
  113. Pai, C. Y., Kuo, T. S., Jaw, T. J., Kurant, E., Chen, C. T., Bessarab, D. A., et al. (1998). The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila. Genes & Development, 12(3), 435–446.CrossRefGoogle Scholar
  114. Pan, D., & Rubin, G. M. (1998). Targeted expression of teashirt induces ectopic eyes in Drosophila. Proceedings of the National Academy of Sciences, 95(26), 15508–15512.CrossRefGoogle Scholar
  115. Papayannopoulos, V., Tomlinson, A., Panin, V. M., Rauskolb, C., & Irvine, K. D. (1998). Dorsal-ventral signaling in the Drosophila eye. Science, 281, 2031–2034.Google Scholar
  116. Pappu, K. S., Ostrin, E. J., Middlebrooks, B. W., Sili, B. T., Chen, R., Atkins, M. R., et al. (2005). Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund. Development, 132(12), 2895–2905.PubMedCrossRefGoogle Scholar
  117. Pauli, T., Seimiya, M., Blanco, J., & Gehring, W. J. (2005). Identification of functional sine oculis motifs in the autoregulatory element of its own gene, in the eyeless enhancer and in the signalling gene hedgehog. Development, 132(12), 2771–2782.PubMedCrossRefGoogle Scholar
  118. Peng, H. W., Slattery, M., & Mann, R. S. (2009). Transcription factor choice in the Hippo signaling pathway: Homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc. Genes & Development, 23(19), 2307–2319.CrossRefGoogle Scholar
  119. Penton, A., Selleck, S. B., & Hoffmann, F. M. (1997). Regulation of cell cycle synchronization by decapentaplegic during Drosophila eye development. Science, 275(5297), 203–206.PubMedCrossRefGoogle Scholar
  120. Pereira, P. S., Pinho, S., Johnson, K., Couso, J. P., & Casares, F. (2006). A 3′ cis-regulatory region controls wingless expression in the Drosophila eye and leg primordia. Developmental Dynamics, 235(1), 225–234.PubMedCrossRefGoogle Scholar
  121. Pichaud, F., & Casares, F. (2000). homothorax and iroquois-C genes are required for the establishment of territories within the developing eye disc. Mechanisms of Development, 96(1), 15–25.PubMedCrossRefGoogle Scholar
  122. Pignoni, F., Hu, B., Zavitz, K. H., Xiao, J., Garrity, P. A., & Zipursky, S. L. (1997). The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell, 91(7), 881–891.PubMedCrossRefGoogle Scholar
  123. Posnien, N., Hopfen, C., Hilbrant, M., Ramos-Womack, M., Murat, S., Schonauer, A., et al. (2012). Evolution of eye morphology and rhodopsin expression in the Drosophila melanogaster species subgroup. PLoS ONE, 7(5), e37346.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Potier, D., Davie, K., Hulselmans, G., Naval Sanchez, M., Haagen, L., Huynh-Thu, V. A., et al. (2014). Mapping gene regulatory networks in Drosophila eye development by large-scale transcriptome perturbations and motif inference. Cell Rep, 9(6), 2290–2303.PubMedCrossRefGoogle Scholar
  125. Punzo, C., Plaza, S., Seimiya, M., Schnupf, P., Kurata, S., Jaeger, J., et al. (2004). Functional divergence between eyeless and twin of eyeless in Drosophila melanogaster. Development, 131(16), 3943–3953.PubMedCrossRefGoogle Scholar
  126. Punzo, C., Seimiya, M., Flister, S., Gehring, W. J., & Plaza, S. (2002). Differential interactions of eyeless and twin of eyeless with the sine oculis enhancer. Development, 129(3), 625–634.PubMedGoogle Scholar
  127. Quan, X. J., Ramaekers, A., & Hassan, B. A. (2012). Transcriptional control of cell fate specification: Lessons from the fly retina. Current Topics in Developmental Biology, 98, 259–276.PubMedCrossRefGoogle Scholar
  128. Quiring, R., Walldorf, U., Kloter, U., & Gehring, W. J. (1994). Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science, 265(5173), 785–789.PubMedCrossRefGoogle Scholar
  129. Reynolds-Kenneally, J., & Mlodzik, M. (2005). Notch signaling controls proliferation through cell-autonomous and non-autonomous mechanisms in the Drosophila eye. Dev Biol, 285, 38–48Google Scholar
  130. Richardson, E. C., & Pichaud, F. (2010). Crumbs is required to achieve proper organ size control during Drosophila head development. Development, 137, 641–650.Google Scholar
  131. Rieckhof, G. E., Casares, F., Ryoo, H. D., Abu-Shaar, M., & Mann, R. S. (1997). Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein. Cell, 91(2), 171–183.PubMedCrossRefGoogle Scholar
  132. Rogers, E. M., Brennan, C. A., Mortimer, N. T., Cook, S., Morris, A. R., & Moses, K. (2005). Pointed regulates an eye-specific transcriptional enhancer in the Drosophila hedgehog gene, which is required for the movement of the morphogenetic furrow. Development, 132(21), 4833–4843.PubMedCrossRefGoogle Scholar
  133. Rogulja, D., Rauskolb, C., & Irvine, K. D. (2008). Morphogen control of wing growth through the Fat signaling pathway. Dev Cell, 15, 309–321.Google Scholar
  134. Roignant, J. Y., Legent, K., Janody, F., & Treisman, J. E. (2010). The transcriptional co-factor Chip acts with LIM-homeodomain proteins to set the boundary of the eye field in Drosophila. Development, 137(2), 273–281.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Royet, J., & Finkelstein, R. (1996). hedgehog, wingless and orthodenticle specify adult head development in Drosophila. Development, 122(6), 1849–1858.PubMedGoogle Scholar
  136. Royet, J., & Finkelstein, R. (1997). Establishing primordia in the Drosophila eye-antennal imaginal disc: The roles of decapentaplegic, wingless and hedgehog. Development, 124(23), 4793–4800.PubMedGoogle Scholar
  137. Salzer, C. L., & Kumar, J. P. (2008) Position dependent responses to discontinuities in the retinal determination network. Developmental Biology.Google Scholar
  138. Salzer, C. L., & Kumar, J. P. (2010). Identification of retinal transformation hot spots in developing Drosophila epithelia. PLoS ONE, 5(1), e8510.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Sato, A., & Tomlinson, A. (2007). Dorsal-ventral midline signaling in the developing Drosophila eye. Development, 134, 659–667.Google Scholar
  140. Schlosser, G. (2015). Vertebrate cranial placodes as evolutionary innovations–the ancestor’s tale. Current Topics in Developmental Biology, 111, 235–300.PubMedCrossRefGoogle Scholar
  141. Schomburg, C., Turetzek, N., Schacht, M. I., Schneider, J., Kirfel, P., Prpic, N. M., & Posnien, N. (2015). Molecular characterization and embryonic origin of the eyes in the common house spider Parasteatoda tepidariorum. Evodevo, 6, 15.PubMedPubMedCentralCrossRefGoogle Scholar
  142. Schubiger, G. (1971). Regeneration, duplication and transdetermination in fragments of the leg disc of Drosophila melanogaster. Development Biology, 26(2), 277–295.CrossRefGoogle Scholar
  143. Schubiger, M., Sustar, A., & Schubiger, G. (2010). Regeneration and transdetermination: The role of wingless and its regulation. Development Biology, 347(2), 315–324.CrossRefGoogle Scholar
  144. Seimiya, M., & Gehring, W. J. (2000). The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism. Development, 127(9), 1879–1886.PubMedGoogle Scholar
  145. Silver, S. J., & Rebay, I. (2005). Signaling circuitries in development: Insights from the retinal determination gene network. Development, 132(1), 3–13.PubMedCrossRefGoogle Scholar
  146. Singh, A., & Choi, K. W. (2003). Initial state of the Drosophila eye before dorsoventral specification is equivalent to ventral. Development, 130, 6351–6360.Google Scholar
  147. Singh, A., Kango-Singh, M., & Sun, Y. H. (2002). Eye suppression, a novel function of teashirt, requires Wingless signaling. Development, 129(18), 4271–4280.PubMedGoogle Scholar
  148. Sun, Y., Jan, L. Y., & Jan, Y. N. (1998). Transcriptional regulation of atonal during development of the Drosophila peripheral nervous system. Development, 125(18), 3731–3740.PubMedGoogle Scholar
  149. Sustar, A., & Schubiger, G. (2005). A transient cell cycle shift in Drosophila imaginal disc cells precedes multipotency. Cell, 120(3), 383–393.PubMedCrossRefGoogle Scholar
  150. Suzuki, T., & Saigo, K. (2000). Transcriptional regulation of atonal required for Drosophila larval eye development by concerted action of eyes absent, sine oculis and hedgehog signaling independent of fused kinase and cubitus interruptus. Development, 127(7), 1531–1540.PubMedGoogle Scholar
  151. Tanaka-Matakatsu, M., & Du, W. (2008). Direct control of the proneural gene atonal by retinal determination factors during Drosophila eye development. Development Biology, 313(2), 787–801.CrossRefGoogle Scholar
  152. Tang, C. Y., & Sun, Y. H. (2002). Use of mini-white as a reporter gene to screen for GAL4 insertions with spatially restricted expression pattern in the developing eye in Drosophila. Genesis, 34(1–2), 39–45.PubMedCrossRefGoogle Scholar
  153. Thomas, B. J., Gunning, D. A., Cho, J., & Zipursky, L. (1994). Cell cycle progression in the developing Drosophila eye: Roughex encodes a novel protein required for the establishment of G1. Cell, 77(7), 1003–1014.PubMedCrossRefGoogle Scholar
  154. Thomas, B. J., Zavitz, K. H., Dong, X., Lane, M. E., Weigmann, K., Finley, R. L, Jr., et al. (1997). roughex down-regulates G2 cyclins in G1. Genes & Development, 11(10), 1289–1298.CrossRefGoogle Scholar
  155. Treisman, J. E. (2013). Retinal differentiation in Drosophila. Wiley Interdisciplinary Reviews: Developmental Biology, 2(4), 545–557.PubMedCrossRefGoogle Scholar
  156. Treisman, J. E., & Rubin, G. M. (1995). wingless inhibits morphogenetic furrow movement in the Drosophila eye disc. Development, 121(11), 3519–3527.PubMedGoogle Scholar
  157. Tsai, Y. C., & Sun, Y. H. (2004). Long-range effect of upd, a ligand for Jak/STAT pathway, on cell cycle in Drosophila eye development. Genesis, 39, 141–153.Google Scholar
  158. Vrailas, A. D., & Moses, K. (2006). Smoothened, thickveins and the genetic control of cell cycle and cell fate in the developing Drosophila eye. Mechanisms of Development, 123(2), 151–165.PubMedCrossRefGoogle Scholar
  159. Waddington, C. H. (1957). The strategy of the genes: A discussion of some aspects of theoretical biology. London: Ruskin House/George Allen and Unwin Ltd.Google Scholar
  160. Wang, L. H., Chiu, S. J., & Sun, Y. H. (2008). Temporal switching of regulation and function of eye gone (eyg) in Drosophila eye development. Development Biology, 321(2), 515–527.CrossRefGoogle Scholar
  161. Wartlick, O., Julicher, F., & Gonzalez-Gaitan, M. (2014). Growth control by a moving morphogen gradient during Drosophila eye development. Development, 141(9), 1884–1893.PubMedCrossRefGoogle Scholar
  162. Wartlick, O., Mumcu, P., Kicheva, A., Bittig, T., Seum, C., Julicher, F., et al. (2011). Dynamics of Dpp signaling and proliferation control. Science, 331(6021), 1154–1159.PubMedCrossRefGoogle Scholar
  163. Weasner, B., Salzer, C., & Kumar, J. P. (2007). Sine oculis, a member of the SIX family of transcription factors, directs eye formation. Development Biology, 303(2), 756–771.CrossRefGoogle Scholar
  164. Weasner, B. M., & Kumar, J. P. (2013). Competition among gene regulatory networks imposes order within the eye-antennal disc of Drosophila. Development, 140(1), 205–215.PubMedPubMedCentralCrossRefGoogle Scholar
  165. Wiersdorff, V., Lecuit, T., Cohen, S. M., & Mlodzik, M. (1996). Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye. Development, 122, 2153–2162.Google Scholar
  166. Yang, C. H., Axelrod, J. D., & Simon, M. A. (2002). Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye. Cell, 108, 675–688.Google Scholar
  167. Yang, C. H., Simon, M. A., & McNeill, H. (1999). mirror controls planar polarity and equator formation through repression of fringe expression and through control of cell affinities. Development, 126, 5857–5866.Google Scholar
  168. Yao, J. G., Weasner, B. M., Wang, L. H., Jang, C. C., Weasner, B., Tang, C. Y., Salzer, C. L., Chen, C. H., Hay, B., Sun, Y. H., et al. (2008). Differential requirements for the Pax6(5a) genes eyegone and twin of eyegone during eye development in Drosophila. Dev Biol, 315, 535–551.Google Scholar
  169. Younossi-Hartenstein, A., Tepass, U., & Hartenstein, V. (1993). Embryonic origin of the imaginal discs of the head of Drosophila melanogaster. Development Genes and Evolution, 203(1–2), 60–73.Google Scholar
  170. Zhang, T., Ranade, S., Cai, C. Q., Clouser, C., & Pignoni, F. (2006). Direct control of neurogenesis by selector factors in the fly eye: Regulation of atonal by Ey and So. Development, 133(24), 4881–4889.PubMedCrossRefGoogle Scholar
  171. Zhang, T., Zhou, Q., & Pignoni, F. (2011). Yki/YAP, Sd/TEAD and Hth/MEIS control tissue specification in the Drosophila eye disc epithelium. PLoS ONE, 6(7), e22278.PubMedPubMedCentralCrossRefGoogle Scholar
  172. Zhou, Q., Zhang, T., Jemc, J. C., Chen, Y., Chen, R., Rebay, I., et al. (2014). Onset of atonal expression in Drosophila retinal progenitors involves redundant and synergistic contributions of Ey/Pax6 and So binding sites within two distant enhancers. Development Biology, 386(1), 152–164.CrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.CABD (Andalusian Centre for Developmental Biology), CSIC-Pablo de Olavide University-Junta de AndalucíaSevilleSpain

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