Animal eyes can vary in complexity ranging from a single photoreceptor cell shaded by a pigment cell to elaborate arrays of these basic units, which allow image formation in compound eyes of insects or camera-type eyes of vertebrates. The evolution of the eye requires involvement of several distinct components-photoreceptors, screening pigment and genes orchestrating their proper temporal and spatial organization. Analysis of particular genetic and biochemical components shows that many evolutionary processes have participated in eye evolution. Multiple examples of co-option of crystallins, Galpha protein subunits and screening pigments contrast with the conserved role of opsins and a set of transcription factors governing eye development in distantly related animal phyla. The direct regulation of essential photoreceptor genes by these factors suggests that this regulatory relationship might have been already established in the ancestral photoreceptor cell.

Department of Transcriptional Regulation Institute of Molecular Genetics Academy of Sciences of the Czech Republic Videnska 1083 Prague 4 CZ 14220 Czech Republic

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Acampora D., Avantaggiato V., Tuorto F., Barone P., Reichert H., Finkelstein R., Simeone A.1998Murine Otx1 and Drosophila otd genes share conserved genetic functions required in invertebrate and vertebrate brain development. Development 125, 1691–1702 PubMed

Acampora D., Annino A., Tuorto F., Puelles E., Lucchesi W., Papalia A., Simeone A.2005Otx genes in the evolution of the vertebrate brain. Brain Res. Bull. 66, 410–420 (doi:10.1016/j.brainresbull.2005.02.005) PubMed DOI

Appelbaum L., Gothilf Y.2006Mechanism of pineal-specific gene expression: the role of E-box and photoreceptor conserved elements. Mol. Cell. Endocrinol. 252, 27–33 (doi:10.1016/j.mce.2006.03.021) PubMed DOI

Arenas-Mena C., Wong K. S.2007HeOtx expression in an indirectly developing polychaete correlates with gastrulation by invagination. Dev. Genes Evol. 217, 373–384 (doi:10.1007/s00427-007-0150-7) PubMed DOI

Arendt D.2003Evolution of eyes and photoreceptor cell types. Int. J. Dev. Biol. 47, 563–571 PubMed

Arendt D.2008The evolution of cell types in animals: emerging principles from molecular studies. Nat. Rev. Genet. 9, 868–882 (doi:10.1038/nrg2416) PubMed DOI

Arendt D., Wittbrodt J.2001Reconstructing the eyes of Urbilateria. Phil. Trans. R. Soc. B 356, 1545–1563 PubMed PMC

Arendt D., Tessmar K., De Campos-Baptista M. I., Dorresteijn A., Wittbrodt J.2002Development of pigment-cup eyes in the polychaete Platynereis dumerilii and evolutionary conservation of larval eyes in Bilateria. Development 129, 1143–1154 PubMed

Arendt D., Tessmar-Raible K., Snyman H., Dorresteijn A. W., Wittbrodt J.2004Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain. Science 306, 869–871 (doi:10.1126/science.1099955) PubMed DOI

Bailey T. J., El-Hodiri H., Zhang L., Shah R., Mathers P. H., Jamrich M.2004Regulation of vertebrate eye development by Rx genes. Int. J. Dev. Biol. 48, 761–770 (doi:10.1387/ijdb.041878tb) PubMed DOI

Baumer N., Marquardt T., Stoykova A., Spieler D., Treichel D., Ashery-Padan R., Gruss P.2003Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6. Development 130, 2903–2915 (doi:10.1242/dev.00450) PubMed DOI

Bebenek I. G., Gates R. D., Morris J., Hartenstein V., Jacobs D. K.2004sine oculis in basal Metazoa. Dev. Genes Evol. 214, 342–351 (doi:10.1007/s00427-004-0407-3) PubMed DOI

Bharti K., Liu W., Csermely T., Bertuzzi S., Arnheiter H.2008Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF. Development 135, 1169–1178 (doi:10.1242/dev.014142) PubMed DOI PMC

Bieszke J. A., Braun E. L., Bean L. E., Kang S., Natvig D. O., Borkovich K. A.1999The nop-1 gene of Neurospora crassa encodes a seven transmembrane helix retinal-binding protein homologous to archaeal rhodopsins. Proc. Natl Acad. Sci. USA 96, 8034–8039 (doi:10.1073/pnas.96.14.8034) PubMed DOI PMC

Blackburn D. C., Conley K. W., Plachetzki D. C., Kempler K., Battelle B. A., Brown N. L.2008Isolation and expression of Pax6 and atonal homologues in the American horseshoe crab, Limulus polyphemus. Dev. Dyn. 237, 2209–2219 (doi:10.1002/dvdy.21634) PubMed DOI PMC

Blanck A., Oesterhelt D.1987The halo-opsin gene. II. Sequence, primary structure of halorhodopsin and comparison with bacteriorhodopsin. EMBO J. 6, 265–273 PubMed PMC

Bonini N. M., Leiserson W. M., Benzer S.1993The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 72, 379–395 (doi:10.1016/0092-8674(93)90115-7) PubMed DOI

Bovolenta P., Mallamaci A., Briata P., Corte G., Boncinelli E.1997Implication of OTX2 in pigment epithelium determination and neural retina differentiation. J. Neurosci. 17, 4243–4252 PubMed PMC

Burri M., Tromvoukis Y., Bopp D., Frigerio G., Noll M.1989Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 8, 1183–1190 PubMed PMC

Callaerts P., Munoz-Marmol A. M., Glardon S., Castillo E., Sun H., Li W. H., Gehring W. J., Salo E.1999Isolation and expression of a Pax-6 gene in the regenerating and intact Planarian Dugesia(G)tigrina. Proc. Natl Acad. Sci. USA 96, 558–563 (doi:10.1073/pnas.96.2.558) PubMed DOI PMC

Carl M., Loosli F., Wittbrodt J.2002Six3 inactivation reveals its essential role for the formation and patterning of the vertebrate eye. Development 129, 4057–4063 PubMed

Carosa E., Kozmik Z., Rall J. E., Piatigorsky J.2002Structure and expression of the scallop Omega-crystallin gene. Evidence for convergent evolution of promoter sequences. J. Biol. Chem. 277, 656–664 (doi:10.1074/jbc.M107004200) PubMed DOI

Chen S., Wang Q. L., Nie Z., Sun H., Lennon G., Copeland N. G., Gilbert D. J., Jenkins N. A., Zack D. J.1997Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 19, 1017–1030 (doi:10.1016/S0896-6273(00)80394-3) PubMed DOI

Cheyette B. N., Green P. J., Martin K., Garren H., Hartenstein V., Zipursky S. L.1994The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron 12, 977–996 (doi:10.1016/0896-6273(94)90308-5) PubMed DOI

Chow R. L., Altmann C. R., Lang R. A., Hemmati-Brivanlou A.1999Pax6 induces ectopic eyes in a vertebrate. Development 126, 4213–4222 PubMed

Contin M. A., Verra D. M., Guido M. E.2006An invertebrate-like phototransduction cascade mediates light detection in the chicken retinal ganglion cells. FASEB J. 20, 2648–2650 (doi:10.1096/fj.06-6133fje) PubMed DOI

Cvekl A., Piatigorsky J.1996Lens development and crystallin gene expression: many roles for Pax-6. Bioessays 18, 621–630 (doi:10.1002/bies.950180805) PubMed DOI

Cvekl A., Yang Y., Chauhan B. K., Cveklova K.2004Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens. Int. J. Dev. Biol. 48, 829–844 (doi:10.1387/ijdb.041866ac) PubMed DOI PMC

Czerny T., Halder G., Kloter U., Souabni A., Gehring W. J., Busslinger M.1999Twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol. Cell 3, 297–307 (doi:10.1016/S1097-2765(00)80457-8) PubMed DOI

D'Alessio G.2002The evolution of monomeric and oligomeric betagamma-type crystallins. Facts and hypotheses. Eur. J. Biochem. 269, 3122–3130 (doi:10.1046/j.1432-1033.2002.03004.x) PubMed DOI

D'Aniello S., et al. 2006The ascidian homolog of the vertebrate homeobox gene Rx is essential for ocellus development and function. Differentiation 74, 222–234 (doi:10.1111/j.1432-0436.2006.00071.x) PubMed DOI

Davis R. J., Tavsanli B. C., Dittrich C., Walldorf U., Mardon G.2003Drosophila retinal homeobox (drx) is not required for establishment of the visual system, but is required for brain and clypeus development. Dev. Biol. 259, 272–287 (doi:10.1016/S0012-1606(03)00201-X) PubMed DOI

de Jong W. W., Hendriks W., Mulders J. W., Bloemendal H.1989Evolution of eye lens crystallins: the stress connection. Trends Biochem. Sci. 14, 365–368 PubMed

de Jong W. W., Leunissen J. A., Voorter C. E.1993Evolution of the alpha-crystallin/small heat-shock protein family. Mol. Biol. Evol. 10, 103–126 PubMed

Dominguez M., Ferres-Marco D., Gutierrez-Avino F. J., Speicher S. A., Beneyto M.2004Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster. Nat. Genet. 36, 31–39 (doi:10.1038/ng1281) PubMed DOI

Dong Y., Friedrich M.2005Comparative analysis of Wingless patterning in the embryonic grasshopper eye. Dev. Genes Evol. 215, 177–197 (doi:10.1007/s00427-004-0465-6) PubMed DOI

Dong Y., Friedrich M.In press Enforcing biphasic visual system development in a directly developing insect by transient knockdown of single eye selector genes. J. Exp. Zool. (Mol. Dev. Evol.) PubMed

Duncan M. K., Cvekl A., Kantorow M., Piatigorsky J.2004Lens crystallins New York, NY: Cambridge University Press

Eakin R. M.1979Evolutionary significance of photoreceptors—retrospect. Am. Zool. 19, 647–653

Finkelstein R., Smouse D., Capaci T. M., Spradling A. C., Perrimon N.1990The orthodenticle gene encodes a novel homeo domain protein involved in the development of the Drosophila nervous system and ocellar visual structures. Genes Dev. 4, 1516–1527 (doi:10.1101/gad.4.9.1516) PubMed DOI

Friedrich M.2006Ancient mechanisms of visual sense organ development based on comparison of the gene networks controlling larval eye, ocellus, and compound eye specification in Drosophila. Arthropod Struct. Dev. 35, 357–378 (doi:10.1016/j.asd.2006.08.010) PubMed DOI

Fu W., Noll M.1997The Pax2 homolog sparkling is required for development of cone and pigment cells in the Drosophila eye. Genes Dev. 11, 2066–2078 (doi:10.1101/gad.11.16.2066) PubMed DOI PMC

Furukawa T., Morrow E. M., Cepko C. L.1997Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 91, 531–541 (doi:10.1016/S0092-8674(00)80439-0) PubMed DOI

Gehring W. J., Ikeo K.1999Pax 6: mastering eye morphogenesis and eye evolution. Trends Genet. 15, 371–377 (doi:10.1016/S0168-9525(99)01776-X) PubMed DOI

Germot A., Lecointre G., Plouhinec J. L., Le Mentec C., Girardot F., Mazan S.2001Structural evolution of Otx genes in craniates. Mol. Biol. Evol. 18, 1668–1678 PubMed

Glardon S., Callaerts P., Halder G., Gehring W. J.1997Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata. Development 124, 817–825 PubMed

Glardon S., Holland L. Z., Gehring W. J., Holland N. D.1998Isolation and developmental expression of the amphioxus Pax-6 gene (AmphiPax-6): insights into eye and photoreceptor evolution. Development 125, 2701–2710 PubMed

Graham D. M., Wong K. Y., Shapiro P., Frederick C., Pattabiraman K., Berson D. M.2008Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade. J. Neurophysiol. 99, 2522–2532 (doi:10.1152/jn.01066.2007) PubMed DOI

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

Hadrys T., Desalle R., Sagasser S., Fischer N., Schierwater B.2005The Trichoplax PaxB gene: a putative Proto-PaxA/B/C gene predating the origin of nerve and sensory cells. Mol. Biol. Evol. 22, 1569–1578 (doi:10.1093/molbev/msi150) PubMed DOI

Halder G., Callaerts P., Gehring W. J.1995Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267, 1788–1792 (doi:10.1126/science.7892602) PubMed DOI

Hallsson J. H., Haflidadottir B. S., Stivers C., Odenwald W., Arnheiter H., Pignoni F., Steingrimsson E.2004The basic helix–loop–helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development. Genetics 167, 233–241 (doi:10.1534/genetics.167.1.233) PubMed DOI PMC

Hartmann B., Lee P. N., Kang Y. Y., Tomarev S., De Couet H. G., Callaerts P.2003Pax6 in the sepiolid squid Euprymna scolopes: evidence for a role in eye, sensory organ and brain development. Mech. Dev. 120, 177–183 (doi:10.1016/S0925-4773(02)00456-2) PubMed DOI

Heanue T. A., Reshef R., Davis R. J., Mardon G., Oliver G., Tomarev S., Lassar A. B., Tabin C. J.1999Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes Dev. 13, 3231–3243 (doi:10.1101/gad.13.24.3231) PubMed DOI PMC

Hennig A. K., Peng G. H., Chen S.2008Regulation of photoreceptor gene expression by Crx-associated transcription factor network. Brain Res. 1192, 114–133 (doi:10.1016/j.brainres.2007.06.036) PubMed DOI PMC

Hill R. E., et al. 1991Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354, 522–525 (doi:10.1038/354522a0) PubMed DOI

Hodgkinson C. A., Moore K. J., Nakayama A., Steingrimsson E., Copeland N. G., Jenkins N. A., Arnheiter H.1993Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix–loop–helix-zipper protein. Cell 74, 395–404 PubMed

Holland L. Z., et al. 2008The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res. 18, 1100–1111 (doi:10.1101/gr.073676.107) PubMed DOI PMC

Horwitz J.1992Alpha-crystallin can function as a molecular chaperone. Proc. Natl Acad. Sci. USA 89, 10 449–10 453 (doi:10.1073/pnas.89.21.10449) PubMed DOI PMC

Hoshiyama D., Suga H., Iwabe N., Koyanagi M., Nikoh N., Kuma K., Matsuda F., Honjo T., Miyata T.1998Sponge Pax cDNA related to Pax-2/5/8 and ancient gene duplications in the Pax family. J Mol Evol 47, 640–648 (doi:10.1007/PL00006421) PubMed DOI

Ingolia T. D., Craig E. A.1982Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin. Proc. Natl Acad. Sci. USA 79, 2360–2364 (doi:10.1073/pnas.79.7.2360) PubMed DOI PMC

Jang C. C., et al. 2003Two Pax genes, eye gone and eyeless, act cooperatively in promoting Drosophila eye development. Development 130, 2939–2951 (doi:10.1242/dev.00522) PubMed DOI

Kasahara T., Okano T., Haga T., Fukada Y.2002Opsin-G11-mediated signaling pathway for photic entrainment of the chicken pineal circadian clock. J. Neurosci. 22, 7321–7325 PubMed PMC

Kawakami K., Sato S., Ozaki H., Ikeda K.2000Six family genes—structure and function as transcription factors and their roles in development. Bioessays 22, 616–626 (doi:10.1002/1521-1878(200007)22:7<616::AID-BIES4>3.0.CO;2-R) PubMed DOI

Kimura A., Singh D., Wawrousek E. F., KIkuchi M., Nakamura M., Shinohara T.2000Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression. J. Biol. Chem. 275, 1152–1160 (doi:10.1074/jbc.275.2.1152) PubMed DOI

Kobayashi M., Nishikawa K., Suzuki T., Yamamoto M.2001The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation. Dev. Biol. 232, 315–326 (doi:10.1006/dbio.2001.0185) PubMed DOI

Koike C., et al. 2007Functional roles of Otx2 transcription factor in postnatal mouse retinal development. Mol. Cell. Biol. 27, 8318–8329 (doi:10.1128/MCB.01209-07) PubMed DOI PMC

Kojima D., Terakita A., Ishikawa T., Tsukahara Y., Maeda A., Shichida Y.1997A novel Go-mediated phototransduction cascade in scallop visual cells. J. Biol. Chem. 272, 22 979–22 982 (doi:10.1074/jbc.272.37.22979) PubMed DOI

Kondoh H., Uchikawa M., Kamachi Y.2004Interplay of Pax6 and SOX2 in lens development as a paradigm of genetic switch mechanisms for cell differentiation. Int. J. Dev. Biol. 48, 819–827 (doi:10.1387/ijdb.041868hk) PubMed DOI

Koyanagi M., Kubokawa K., Tsukamoto H., Shichida Y., Terakita A.2005Cephalochordate melanopsin: evolutionary linkage between invertebrate visual cells and vertebrate photosensitive retinal ganglion cells. Curr. Biol. 15, 1065–1069 (doi:10.1016/j.cub.2005.04.063) PubMed DOI

Koyanagi M., Takano K., Tsukamoto H., Ohtsu K., Tokunaga F., Terakita A.2008Jellyfish vision starts with cAMP signaling mediated by opsin-Gs cascade. Proc. Natl Acad. Sci. USA 105, 15 576–15 580 (doi:10.1073/pnas.0806215105) PubMed DOI PMC

Kozmik Z.2005Pax genes in eye development and evolution. Curr. Opin. Genet. Dev. 15, 430–438 (doi:10.1016/j.gde.2005.05.001) PubMed DOI

Kozmik Z., Daube M., Frei E., Norman B., Kos L., Dishaw L. J., Noll M., Piatigorsky J.2003Role of Pax genes in eye evolution: a cnidarian PaxB gene uniting Pax2 and Pax6 functions. Dev. Cell 5, 773–785 (doi:10.1016/S1534-5807(03)00325-3) PubMed DOI

Kozmik Z., et al. 2007Pax–Six–Eya–Dach network during amphioxus development: conservation in vitro but context specificity in vivo. Dev. Biol. 306, 143–159 (doi:10.1016/j.ydbio.2007.03.009) PubMed DOI

Kozmik Z., et al. 2008aAssembly of the cnidarian camera-type eye from vertebrate-like components. Proc. Natl Acad. Sci. USA 105, 8989–8993 (doi:10.1073/pnas.0800388105) PubMed DOI PMC

Kozmik Z., Swamynathan S. K., Ruzickova J., Jonasova K., Paces V., Vlcek C., Piatigorsky J.2008bCubozoan crystallins: evidence for convergent evolution of pax regulatory sequences. Evol Dev 10, 52–61 PubMed

Kronhamn J., Frei E., Daube M., Jiao R., Shi Y., Noll M., Rasmuson-Lestander A.2002Headless flies produced by mutations in the paralogous Pax6 genes eyeless and twin of eyeless. Development 129, 1015–1026 PubMed

Lacalli T. C.2004Sensory systems in amphioxus: a window on the ancestral chordate condition. Brain Behav. Evol. 64, 148–162 (doi:10.1159/000079744) PubMed DOI

Land M., Nilsson E.2002Animal eyes New York, NY: Oxford University Press

Larusso N. D., Rutterberg B. E., Singh A. K., Oakley T. H.2008Type II opsins: evolutionary origin by internal domain duplication? J. Mol. Evol. 66, 417–423 (doi:10.1007/s00239-008-9076-6) PubMed DOI

Li X., Perissi V., Liu F., Rose D. W., Rosenfeld M. G.2002Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science 297, 1180–1183 PubMed

Li X., et al. 2003Eya protein phosphatase activity regulates Six1–Dach–Eya transcriptional effects in mammalian organogenesis. Nature 426, 247–254 (doi:10.1038/nature02083) PubMed DOI

Liu W., Lagutin O. V., Mende M., Streit A., Oliver G.2006Six3 activation of Pax6 expression is essential for mammalian lens induction and specification. EMBO J. 25, 5383–5395 (doi:10.1038/sj.emboj.7601398) PubMed DOI PMC

Loosli F., Kmita-Cunisse M., Gehring W. J.1996Isolation of a Pax-6 homolog from the ribbonworm Lineus sanguineus. Proc. Natl Acad. Sci. USA 93, 2658–2663 (doi:10.1073/pnas.93.7.2658) PubMed DOI PMC

Loosli F., Staub W., Finger-Baier K. C., Ober E. A., Verkade H., Wittbrodt J., Baier H.2003Loss of eyes in zebrafish caused by mutation of chokh/rx3. EMBO Rep. 4, 894–899 (doi:10.1038/sj.embor.embor919) PubMed DOI PMC

Lopez-Rios J., Tessmar K., Loosli F., Wittbrodt J., Bovolenta P.2003Six3 and Six6 activity is modulated by members of the groucho family. Development 130, 185–195 (doi:10.1242/dev.00185) PubMed DOI

Manavathi B., et al. 2007Repression of Six3 by a corepressor regulates rhodopsin expression. Proc. Natl Acad. Sci. USA 104, 13 128–13 133 (doi:10.1073/pnas.0705878104) PubMed DOI PMC

Mannini L., Rossi L., Deri P., Gremigni V., Salvetti A., Salo E., Batistoni R.2004Djeyes absent (Djeya) controls prototypic planarian eye regeneration by cooperating with the transcription factor Djsix-1. Dev. Biol. 269, 346–359 (doi:10.1016/j.ydbio.2004.01.042) PubMed DOI

Martinez-Morales J. R., Signore M., Acampora D., Simeone A., Bovolenta P.2001Otx genes are required for tissue specification in the developing eye. Development 128, 2019–2030 PubMed

Martinez-Morales J. R., Dolez V., Rodrigo I., Zaccarini R., Leconte L., Bovolenta P., Saule S.2003OTX2 activates the molecular network underlying retina pigment epithelium differentiation. J. Biol. Chem. 278, 21 721–21 731 (doi:10.1074/jbc.M301708200) PubMed DOI

Martinez-Morales J. R., Rodrigo I., Bovolenta P.2004Eye development: a view from the retina pigmented epithelium. Bioessays 26, 766–777 PubMed

Mathers P. H., Grinberg A., Mahon K. A., Jamrich M.1997The Rx homeobox gene is essential for vertebrate eye development. Nature 387, 603–607 (doi:10.1038/42475) PubMed DOI

Milligan G., Kostenis E.2006Heterotrimeric G-proteins: a short history. Br. J. Pharmacol. 147(Suppl. 1), S46–S55 PubMed PMC

Murisier F., Beermann F.2006Genetics of pigment cells: lessons from the tyrosinase gene family. Histol. Histopathol. 21, 567–578 PubMed

Nagao T., Leuzinger S., Acampora D., Simeone A., Finkelstein R., Reichert H., Furukubo-Tokunaga K.1998Developmental rescue of Drosophila cephalic defects by the human Otx genes. Proc. Natl Acad. Sci. USA 95, 3737–3742 (doi:10.1073/pnas.95.7.3737) PubMed DOI PMC

Nagel G., Ollig D., Fuhrmann M., Kateriya S., Musti A. M., BAmberg E., Hegemann P.2002Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296, 2395–2398 (doi:10.1126/science.1072068) PubMed DOI

Nishida A., Furukawa A., Koike C., Tano Y., Aizawa S., Matsuo I., Furukawa T.2003Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat. Neurosci. 6, 1255–1263 (doi:10.1038/nn1155) PubMed DOI

Nordstrom K., Larsson T. A., Larhammar D.2004Extensive duplications of phototransduction genes in early vertebrate evolution correlate with block (chromosome) duplications. Genomics 83, 852–872 (doi:10.1016/j.ygeno.2003.11.008) PubMed DOI

Ohto H., Kamada S., Tago K., Tominaga S. I., Ozaki H., Sato S., Kawakami K.1999Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya. Mol. Cell. Biol. 19, 6815–6824 PubMed PMC

Ozaki H., et al. 2004Six1 controls patterning of the mouse otic vesicle. Development 131, 551–562 (doi:10.1242/dev.00943) PubMed DOI

Pan Y., Nekkalapudi S., Kelly L. E., El-Hodiri H. M.2006The Rx-like homeobox gene (Rx-L) is necessary for normal photoreceptor development. Invest. Ophthalmol. Vis. Sci. 47, 4245–4253 (doi:10.1167/iovs.06-0167) PubMed DOI PMC

Panda S., Nayak S. K., Campo B., Walker J. R., Hogenesch J. B., Jegla T.2005Illumination of the melanopsin signaling pathway. Science 307, 600–604 (doi:10.1126/science.1105121) PubMed DOI

Pappu K. S., Mardon G.2004Genetic control of retinal specification and determination in Drosophila. Int. J. Dev. Biol. 48, 913–924 (doi:10.1387/ijdb.041875kp) PubMed DOI

Piatigorsky J.2007Gene sharing and evolution: the diversity of protein functions Cambridge, MA: Harvard University Press

Piatigorsky J., Wistow G.1991The recruitment of crystallins: new functions precede gene duplication. Science 252, 1078–1079 (doi:10.1126/science.252.5009.1078) PubMed DOI

Piatigorsky J., Wistow G. J.1989Enzyme/crystallins: gene sharing as an evolutionary strategy. Cell 57, 197–199 (doi:10.1016/0092-8674(89)90956-2) PubMed DOI

Piatigorsky J., O'Brien W. E., Norman B. L., Kalumuck K., Wistow G. J., Borras T., Nickerson J. M., Wawrousek E. F.1988Gene sharing by delta-crystallin and argininosuccinate lyase. Proc. Natl Acad. Sci. USA 85, 3479–3483 (doi:10.1073/pnas.85.10.3479) PubMed DOI PMC

Piatigorsky J., Kozmik Z., Horwitz J., Ding L., Carosa E., Robison W. G., JR, Steinbach P. J., Tamm E. R.2000Omega-crystallin of the scallop lens. A dimeric aldehyde dehydrogenase class 1/2 enzyme-crystallin. J. Biol. Chem. 275, 41 064–41 073 (doi:10.1074/jbc.M005625200) PubMed DOI

Pineda D., et al. 2002The genetic network of prototypic planarian eye regeneration is Pax6 independent. Development 129, 1423–1434 PubMed

Plachetzki D. C., Oakley T. H.2007Key transitions during the evolution of animal phototransduction: novelty, ‘tree-thinking,’ co-option, and co-duplication. Integr. Comp. Biol. 47, 759–769 (doi:10.1093/icb/icm050) PubMed DOI

Plachetzki D. C., Degnan B. M., Oakley T. H.2007The origins of novel protein interactions during animal opsin evolution. PLoS ONE 2, e1054 (doi:10.1371/journal.pone.0001054) PubMed DOI PMC

Plouhinec J. L., et al. 2003The mammalian Crx genes are highly divergent representatives of the Otx5 gene family, a gnathostome orthology class of orthodenticle-related homeogenes involved in the differentiation of retinal photoreceptors and circadian entrainment. Mol. Biol. Evol. 20, 513–521 (doi:10.1093/molbev/msg085) PubMed DOI

Plouhinec J. L., Leconte L., Sauka-Spengler T., Bovolenta P., Mazan S., Saule S.2005Comparative analysis of gnathostome Otx gene expression patterns in the developing eye: implications for the functional evolution of the multigene family. Dev. Biol. 278, 560–575 (doi:10.1016/j.ydbio.2004.11.019) PubMed DOI

Qian J., Esumi N., Chen Y., Wang Q., Chowers I., Zack D. J.2005Identification of regulatory targets of tissue-specific transcription factors: application to retina-specific gene regulation. Nucleic Acids Res. 33, 3479–3491 (doi:10.1093/nar/gki658) PubMed DOI PMC

Quigley I. K., Xie X., Shankland M.2007Hau-Pax6A expression in the central nervous system of the leech embryo. Dev. Genes Evol. 217, 459–468 (doi:10.1007/s00427-007-0156-1) PubMed DOI

Quiring R., Walldorf U., Kloter U., Gehring W. J.1994Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265, 785–789 (doi:10.1126/science.7914031) PubMed DOI

Radu R. A., Hu J., Peng J., Bok D., Mata N. L., Travis G. H.2008Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells. J. Biol. Chem. 283, 19 730–19 738 (doi:10.1074/jbc.M801288200) PubMed DOI PMC

Raible F., Tessmar-Raible K., Arboleda E., Kaller T., Bork P., Arendt D., Arnone M. I.2006Opsins and clusters of sensory G-protein-coupled receptors in the sea urchin genome. Dev. Biol. 300, 461–475 (doi:10.1016/j.ydbio.2006.08.070) PubMed DOI

Ranade S. S., Yang-Zhou D., Kong S. W., Mcdonald E. C., Cook T. A., Pignoni F.2008Analysis of the Otd-dependent transcriptome supports the evolutionary conservation of CRX/OTX/OTD functions in flies and vertebrates. Dev. Biol. 315, 521–534 (doi:10.1016/j.ydbio.2007.12.017) PubMed DOI PMC

Rath M. F., Morin F., Shi Q., Klein D. C., Moller M.2007Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat. Exp. Eye Res. 85, 65–73 (doi:10.1016/j.exer.2007.02.016) PubMed DOI

Rayapureddi J. P., Kattamuri C., Steinmetz B. D., Frankfort B. J., Ostrin E. J., Mardon G., Hegde R. S.2003Eyes absent represents a class of protein tyrosine phosphatases. Nature 426, 295–298 (doi:10.1038/nature02093) PubMed DOI

Royet J., Finkelstein R.1995Pattern formation in Drosophila head development: the role of the orthodenticle homeobox gene. Development 121, 3561–3572 PubMed

Salo E., Pineda D., Marsal M., Gonzalez J., Gremigni V., Batistoni R.2002Genetic network of the eye in Platyhelminthes: expression and functional analysis of some players during planarian regeneration. Gene 287, 67–74 (doi:10.1016/S0378-1119(01)00863-0) PubMed DOI

Schwarz M., Cecconi F., Bernier G., Andrejewski N., Kammandel B., Wagner M., Gruss P.2000Spatial specification of mammalian eye territories by reciprocal transcriptional repression of Pax2 and Pax6. Development 127, 4325–4334 PubMed

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

Silver S. J., Rebay I.2005Signaling circuitries in development: insights from the retinal determination gene network. Development 132, 3–13 (doi:10.1242/dev.01539) PubMed DOI

Simeone A., Puelles E., Acampora D.2002The Otx family. Curr. Opin. Genet. Dev. 12, 409–415 (doi:10.1016/S0959-437X(02)00318-0) PubMed DOI

Simpson T. I., Price D. J.2002Pax6; a pleiotropic player in development. Bioessays 24, 1041–1051 (doi:10.1002/bies.10174) PubMed DOI

Spudich J. L., Yang C. S., Jung K. H., Spudich E. N.2000Retinylidene proteins: structures and functions from archaea to humans. Annu. Rev. Cell Dev. Biol. 16, 365–392 (doi:10.1146/annurev.cellbio.16.1.365) PubMed DOI

Steingrimsson E., Copeland N. G., Jenkins N. A.2004Melanocytes and the microphthalmia transcription factor network. Annu. Rev. Genet. 38, 365–411 (doi:10.1146/annurev.genet.38.072902.092717) PubMed DOI

Stierwald M., Yanze N., Bamert R. P., Kammermeier L., Schmid V.2004The Sine oculis/Six class family of homeobox genes in jellyfish with and without eyes: development and eye regeneration. Dev. Biol. 274, 70–81 (doi:10.1016/j.ydbio.2004.06.018) PubMed DOI

Su C. Y., Luo D. G., Terakita A., Shichida Y., Liao H. W., Kazmi M. A., Sakmar T. P., Yau K. W.2006Parietal-eye phototransduction components and their potential evolutionary implications. Science 311, 1617–1621 (doi:10.1126/science.1123802) PubMed DOI

Suga H., Schmid V., Gehring W. J.2008Evolution and functional diversity of jellyfish opsins. Curr. Biol. 18, 51–55 (doi:10.1016/j.cub.2007.11.059) PubMed DOI

Suzuki M. M., Satoh N.2000Genes expressed in the amphioxus notochord revealed by EST analysis. Dev. Biol. 224, 168–177 (doi:10.1006/dbio.2000.9796) PubMed DOI

Suzuki T., Terakita A., Narita K., Nagai K., Tsukahara Y., Kito Y.1995Squid photoreceptor phospholipase C is stimulated by membrane Gq alpha but not by soluble Gq alpha. FEBS Lett. 377, 333–337 (doi:10.1016/0014-5793(95)01364-4) PubMed DOI

Tahayato A., Sonneville R., Pichaud F., Wernet M. F., Papatsenko D., Beaufils P., Cook T., Desplan C.2003Otd/Crx, a dual regulator for the specification of ommatidia subtypes in the Drosophila retina. Dev. Cell 5, 391–402 (doi:10.1016/S1534-5807(03)00239-9) PubMed DOI

Takeda K., Yokoyama S., Yasumoto K., Saito H., Udono T., Takahashi K., Shibahara S.2003OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium. Biochem. Biophys. Res. Commun. 300, 908–914 (doi:10.1016/S0006-291X(02)02934-0) PubMed DOI

Takechi M., Seno S., Kawamura S.2008Identification of cis-acting elements repressing blue opsin expression in zebrafish UV cones and pineal cells. J. Biol. Chem 283, 31 625–31 632 (doi:10.1074/jbc.M806226200) PubMed DOI

Terakita A.2005The opsins. Genome Biol. 6, 213 (doi:10.1186/gb-2005-6-3-213) PubMed DOI PMC

Tomarev S. I., Callaerts P., Kos L., Zinovieva R., Halder G., Gehring W., Piatigorsky J.1997Squid Pax-6 and eye development. Proc. Natl Acad. Sci. USA 94, 2421–2426 (doi:10.1073/pnas.94.6.2421) PubMed DOI PMC

Tootle T. L., Silver S. J., Davies E. L., Newman V., Latek R. R., Mills I. A., Selengut J. D., Parlikar B. E., Rebay I.2003The transcription factor Eyes absent is a protein tyrosine phosphatase. Nature 426, 299–302 (doi:10.1038/nature02097) PubMed DOI

Toyoda R., Sato S., Ikeo K., Gojobori T., Numakunai T., Goding C. R., Yamamoto H.2000Pigment cell-specific expression of the tyrosinase gene in ascidians has a different regulatory mechanism from vertebrates. Gene 259, 159–170 (doi:10.1016/S0378-1119(00)00433-9) PubMed DOI

Toyoda R., Kasai A., Sato S., Wada S., Saiga H., Ikeo K., Gojobori T., Numakunai T., Yamamoto H.2004Pigment cell lineage-specific expression activity of the ascidian tyrosinase-related gene. Gene 332, 61–69 (doi:10.1016/j.gene.2004.01.030) PubMed DOI

Treisman J., Harris E., Desplan C.1991The paired box encodes a second DNA-binding domain in the paired homeo domain protein. Genes Dev. 5, 594–604 (doi:10.1101/gad.5.4.594) PubMed DOI

Umesono Y., Watanabe K., Agata K.1999Distinct structural domains in the planarian brain defined by the expression of evolutionarily conserved homeobox genes. Dev. Genes Evol. 209, 31–39 (doi:10.1007/s004270050224) PubMed DOI

Vandendries E. R., Johnson D., Reinke R.1996orthodenticle is required for photoreceptor cell development in the Drosophila eye. Dev. Biol. 173, 243–255 (doi:10.1006/dbio.1996.0020) PubMed DOI

Velarde R. A., Sauer C. D., Walden K. K., Fahrbach S. E., Robertson H. M.2005Pteropsin: a vertebrate-like non-visual opsin expressed in the honey bee brain. Insect Biochem. Mol. Biol. 35, 1367–1377 (doi:10.1016/j.ibmb.2005.09.001) PubMed DOI

Wada S., Katsuyama Y., Sato Y., Itoh C., Saiga H.1996Hroth an orthodenticle-related homeobox gene of the ascidian, Halocynthia roretzi: its expression and putative roles in the axis formation during embryogenesis. Mech. Dev. 60, 59–71 (doi:10.1016/S0925-4773(96)00600-4) PubMed DOI

Wada S., Toyoda R., Yamamoto H., Saiga H.2002Ascidian otx gene Hroth activates transcription of the brain-specific gene HrTRP. Dev. Dyn. 225, 46–53 (doi:10.1002/dvdy.10135) PubMed DOI

Wada S., et al. 2003A genomewide survey of developmentally relevant genes in Ciona intestinalis. II. Genes for homeobox transcription factors. Dev. Genes Evol. 213, 222–234 (doi:10.1007/s00427-003-0321-0) PubMed DOI

Wang Q. L., et al. 2004QRX, a novel homeobox gene, modulates photoreceptor gene expression. Hum. Mol. Genet. 13, 1025–1040 (doi:10.1093/hmg/ddh117) PubMed DOI

Williams N. A., Holland P. W. H.1996Old head on young shoulders. Nature 383, 490–490 (doi:10.1038/383490a0) DOI

Williams N. A., Holland P. W.1998Gene and domain duplication in the chordate Otx gene family: insights from amphioxus Otx. Mol. Biol. Evol. 15, 600–607 PubMed

Wistow G.1990Evolution of a protein superfamily: relationships between vertebrate lens crystallins and microorganism dormancy proteins. J. Mol. Evol. 30, 140–145 (doi:10.1007/BF02099940) PubMed DOI

Wistow G. J., Piatigorsky J.1988Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. Annu. Rev. Biochem. 57, 479–504 (doi:10.1146/annurev.bi.57.070188.002403) PubMed DOI

Xu Z. P., Saunders G. F.1997Transcriptional regulation of the human PAX6 gene promoter. J. Biol. Chem. 272, 3430–3436 PubMed

Xu P. X., Adams J., Peters H., Brown M. C., Heaney S., Maas R.1999Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat. Genet. 23, 113–117 PubMed

Yajima I., et al. 2003Cloning and functional analysis of ascidian Mitf in vivo: insights into the origin of vertebrate pigment cells. Mech. Dev. 120, 1489–1504 (doi:10.1016/j.mod.2003.08.009) PubMed DOI

Yoshida R., Kusakabe T., Kamatani M., Daitoh M., Tsuda M.2002Central nervous system-specific expression of G protein alpha subunits in the ascidian Ciona intestinalis. Zool. Sci. 19, 1079–1088 (doi:10.2108/zsj.19.1079) PubMed DOI

Zhang X., Friedman A., Heaney S., Purcell P., Maas R. L.2002Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis. Genes Dev. 16, 2097–2107 (doi:10.1101/gad.1007602) PubMed DOI PMC

Zhu C. C., Dyer M. A., Uchikawa M., Kondoh H., Lagutin O. V., Oliver G.2002Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. Development 129, 2835–2849 PubMed

Ziegler I.2003The pteridine pathway in zebrafish: regulation and specification during the determination of neural crest cell-fate. Pigment Cell Res. 16, 172–182 (doi:10.1034/j.1600-0749.2003.00044.x) PubMed DOI

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

Zuber M. E., Perron M., Philpott A., Bang A., Harris W. A.1999Giant eyes in Xenopus laevis by overexpression of XOptx2. Cell 98, 341–352 (doi:10.1016/S0092-8674(00)81963-7) PubMed DOI