Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development

Human Molecular Genetics

Volumn 14, Issue 22, 2005, Pages 3347-3359

  Evans, Amanda L ^a   Gage, Philip J ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR PITX2;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTERIOR EYE SEGMENT; ARTICLE; AXENFELD RIEGER SYNDROME; CELL DIFFERENTIATION; CONTROLLED STUDY; CORNEA ENDOTHELIUM; CORNEA STROMA; EYE DEVELOPMENT; EYE DISEASE; GENE EXPRESSION; GENE FUNCTION; GLAUCOMA; HOMEOBOX; HYPOTHALAMUS; KNOCKOUT MOUSE; MOUSE; NEURAL CREST; NONHUMAN; OCULAR BLOOD VESSEL; OPTIC NERVE; PATHOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; SCLERA; STEM CELL;

ANIMALS; ANOPHTHALMOS; EYE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HOMEODOMAIN PROTEINS; MESODERM; MICE; MICE, KNOCKOUT; NEURAL CREST; NUCLEAR PROTEINS; OPTIC NERVE; PIGMENT EPITHELIUM OF EYE; TRANSCRIPTION FACTORS;

ANIMALIA;

EID: 27944471886     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddi365     Document Type: Article

References (109)

1. Araie, M., Sekine, M., Suzuki, Y. and Koseki, N. (1994) Factors contributing to the progression of visual field damage in eyes with normal-tension glaucoma. Ophthalmology, 101, 1440-1444.
2. Grodum, K., Heijl, A. and Bengtsson, B. (2005) Risk of glaucoma in ocular hypertension with and without pseudoexfoliation. Ophthalmology, 112, 386-390.
3. Semina, E.V., Reiter, R., Leysens, N.J., Alward, W.L., Small, K.W., Datson, N.A., Siegel-Bartelt, J., Bierke-Nelson, D., Bitoun, P., Zabel, B.U. et al. (1996) Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat. Genet., 14, 392-399.
4. Kulak, S.C., Kozlowski, K., Semina, E.V., Pearce, W.G. and Walter, M.A. (1998) Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. Hum. Mol. Genet., 7, 1113-1117.
5. Alward, W.L., Semina, E.V., Kalenak, J.W., Heon, E., Sheth, B.P., Stone, E.M. and Murray, J.C. (1998) Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene. Am. J. Ophthalmol., 125, 98-100.
6. Shields, M.B. (1983) Axenfeld-Rieger syndrome: A theory of mechanism and distinctions from the iridocorneal endothelial syndrome. Trans. Am. Ophthalmol. Soc., 81, 736-784.
7. Noden, D.M. (1982) Periocular mesenchyme: Neural crest and mesodermal interactions. In Jacobiec, F.A. (ed.) Oculan Anatomy, Embrology, and Teratology, Harper and Row, Hagerstown, MD, pp. 97-119.
8. Vadlamudi, U., Espinoza, H.M., Ganga, M., Martin, D.M., Liu, X., Engelhardt, J.F. and Amendt, B.A. (2005) PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter. J. Cell Sci., 118, 1129-1137.
9. Ganga, M., Espinoza, H.M., Cox, C.J., Morton, L., Hjalt, T.A., Lee, Y. and Amendt, B.A. (2003) PITX2 isoform-specific regulation of atrial natriuretic factor expression: Synergism and repression with Nkx2.5. J. Biol. Chem., 278, 22437-22445.
10. Green, P.D., Hjalt, T.A., Kirk, D.E., Sutherland, L.B., Thomas, B.L., Sharpe, P.T., Snead, M.L., Murray, J.C., Russo, A.F. and Amendt, B.A. (2001) Antagonistic regulation of Dlx2 expression by PITX2 and Msx2: implications for tooth development. Gene. Expr., 9, 265-281.
11. Hjalt, T.A., Amendt, B.A. and Murray, J.C. (2001) PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: Implications for the pathology of Rieger syndrome. J. Cell Biol., 152, 545-552.
12. Cox, C.J., Espinoza, H.M., McWilliams, B., Chappell, K., Morton, L., Hjalt, T.A., Semina, E.V. and Amendt, B.A. (2002) Differential regulation of gene expression by PITX2 isoforms. J. Biol. Chem., 277, 25001-25010.
13. Amendt, B.A., Sutherland, L.B., Semina, E.V. and Russo, A.F. (1998) The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities. J. Biol. Chem., 273, 20066-20072.
14. Charles, M.A., Suh, H., Hjalt, T.A., Drouin, J., Camper, S.A. and Gage, P.J. (2005) PITX genes are required for cell survival and Lhx3 activation. Mol. Endocrinol., 19, 1893-1903.
15. Suh, H,, Gage, P.J., Drouin, J. and Camper, S.A. (2002) Pitx2 is required at multiple stages of pituitary organogenesis: Pituitary primordium formation and cell specification. Development, 129, 329-337.
16. Priston, M., Kozlowski, K., Gill, D., Letwin, K., Buys, Y., Levin, A.V., Walter, M.A. and Heon, E. (2001) Functional analyses of two newly identified PITX2 mutants reveal a novel molecular mechanism for Axenfeld-Rieger syndrome. Hum. Mol. Genet., 10, 1631-1638.
17. Brooks, B.P., Moroi, S.E., Downs, C.A., Wiltse, S., Othman, M.I., Semina, E.V. and Richards, J.E. (2004) A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome. Ophthalmic Genet., 25, 57-62.
18. Kozlowski, K. and Walter, M.A. (2000) Variation in residual PITX2 activity underlies the phenotypic spectrum of anterior segment developmental disorders. Hum. Mol. Genet., 9, 2131-2139.
19. Saadi, I., Kuburas, A., Engle, J.J. and Russo, A.F. (2003) Dominant negative dimerization of a mutant homeodomain protein in Axenfeld-Rieger syndrome. Mol. Cell. Biol., 23, 1968-1982.
20. Saadi, I., Semina, E.V., Amendt, B.A., Harris, D.J., Murphy, K.P., Murray, J.C. and Russo, A.F. (2001) Identification of a dominant negative homeodomain mutation in Rieger syndrome. J. Biol. Chem., 276, 23034-23041.
21. Perveen, R., Lloyd, I.C., Clayton-Smith, J., Churchill, A., van Heyningen, V., Hanson, I., Taylor, D., McKeown, C., Super, M., Kerr, B. et al. (2000) Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations. Invest. Ophthalmol. Vis. Sci., 41, 2456-2460.
22. Gage, P.J., Rhoades, W., Prucka, S.K. and Hjalt, T.A. (2005) Fate maps of neural crest and mesoderm in the mammalian eye. Invest. Ophthalmol. Vis. Sci., in press.
23. Levkovitch-Verbin, H. (2004) Animal models of optic nerve diseases. Eye, 18, 1066-1074.
24. Lu, M.F., Pressman, C., Dyer, R., Johnson, R.L. and Martin, J.F. (1999) Function of Rieger syndrome gene in left-right asymmetry and craniofacial development. Nature, 401, 276-278.
25. Gage, P.J., Suh, H. and Camper, S.A. (1999) Dosage requirement of Pitx2 for development of multiple organs. Development, 126, 4643-4651.
26. Lin, C.R., Kioussi, C., O'Connell, S., Briata, P., Szeto, D., Liu, F., Izpisua-Belmonte, J.C. and Rosenfeld, M.G. (1999) Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature, 401, 279-282.
27. Kitamura, K., Miura, H., Miyagawa-Tomita, S., Yanazawa, M., Katoh-Fukui, Y., Suzuki, R., Ohuchi, H., Suehiro, A., Motegi, Y., Nakahara, Y. et al. (1999) Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism. Development, 126, 5749-5758.
28. Johnston, M.C., Noden, D.M., Hazelton, R.D., Coulombre, J.L. and Coulombre, A.J. (1979) Origins of avian ocular and periocular tissues. Exp. Eye Res., 29, 27-43.
29. Le Douarin, N.M. (1980) Migration and differentiation of neural crest cells. In Moscona, A.A. and Monroy, A. (eds), Current Topics in Development, Part II. Academic Press, New York.
30. Le Douarin, N.M. (1982) The Neural Crest. Cambridge University Press, Cambridge.
31. Le Lievre, C.S. and Le Douarin, N.M. (1975) Mesenchymal derivatives of the neural crest: Analysis of chimaeric quail and chick embryos. J. Embryol. Exp. Morphol., 34, 125-154.
32. Kupfer, C. and Kaiser-Kupfer, M.I. (1978) New hypothesis of developmental anomalies of the anterior chamber associated with glaucoma. Trans. Ophthalmol. Soc. UK, 98, 213-215.
33. Danielian, P.S., Muccino, D., Rowitch, D.H., Michael, S.K. and McMahon, A.P. (1999) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr. Biol., 8, 1323-1326.
34. Soriano, P. (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet., 21, 70-71.
35. Echelard, Y., Vassileva, G. and McMahon, A.P. (1994) Cis-acting regulatory sequences governing Wnt-1 expression in the developing mouse CNS. Development, 120, 2213-2224.
36. Gage, P.J. and Camper, S.A. (1997) Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum. Mol. Genet., 6, 457-464.
37. Brault, V., Moore, R., Kutsch, S., Ishibashi, M., Rowitch, D.H., McMahon, A.P., Sommer, L., Boussadia, O. and Kemler, R. (2001) Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development, 128, 1253-1264.
38. Ishikawa, K., Sohmiya, M., Ohguni, S., Sato, T., Tanigawa, K. and Kato, Y. (1996) Unique case of growth hormone (GH) deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus. Am. J. Med. Genet., 67, 191-196.
39. Smith, R.S., Sundberg, J.P. and Linder, C.C. (1997) Mouse mutations as models for studying cataracts. Pathobiology, 65, 146-154.
40. Merville, C., Dosne, A.M. and Caen, J.P. (1976) Vascular subendothelium: structure and functions. Pathol. Biol. (Paris), 24 (suppl), 18-22.
41. Darland, D.C., Massingham, L.J., Smith, S.R., Piek, E., Saint-Geniez, M. and D'Amore, P.A. (2003) Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival. Dev. Biol., 264, 275-288.
42. Hellstrom, M., Kalen, M., Lindahl, P., Abramsson, A. and Betsholtz, C. (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development, 126, 3047-3055.
43. Hirschi, K.K., Rohovsky, S.A. and D'Amore, P.A. (1998) PDGF, TGF-beta, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J. Cell Biol., 141, 805-814.
44. Lindahl, P., Johansson, B.R., Leveen, P. and Betsholtz, C. (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science, 277, 242-245.
45. Nishishita, T. and Lin, P.C. (2004) Angiopoietin 1, PDGF-B, and TGF-beta gene regulation in endothelial cell and smooth muscle cell interaction. J. Cell. Biochem., 91, 584-593.
46. Etchevers, H.C., Vincent, C., Le Douarin, N.M. and Couly, G.F. (2001) The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain. Development, 128, 1059-1068.
47. Ozerdem, U., Grako, K.A., Dahlin-Huppe, K., Monosov, E. and Stallcup, W.B. (2001) NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev. Dyn., 222, 218-227.
48. Hughes, S. and Chan-Ling, T. (2004) Characterization of smooth muscle cell and pericyte differentiation in the rat retina in vivo. Invest. Ophthalmol. Vis. Sci., 45, 2795-2806.
49. Murfee, W.L., Skalak, T.C. and Peirce, S.M. (2005) Differential arterial/ venous expression of NG2 proteoglycan in perivascular cells along microvessels: Identifying a venule-specific phenotype. Microcirculation, 12, 151-160.
50. Torres, M., Gomez-Pardo, E. and Gruss, P. (1996) Pax2 contributes to inner ear patterning and optic nerve trajectory. Development, 122, 3381-3391.
51. Otteson, D.C., Shelden, E., Jones, J.M., Kameoka, J. and Hitchcock, P.F. (1998) Pax2 expression and retinal morphogenesis in the normal and Krd mouse. Dev. Biol., 193, 209-224.
52. Dressler, G.R., Deutsch, U., Chowdhury, K., Nornes, H.O. and Gruss, P. (1990) Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development, 109, 787-795.
53. Bertuzzi, S., Hindges, R., Mui, S.H., O'Leary, D.D. and Lemke, G. (1999) The homeodomain protein vax1 is required for axon guidance and major tract formation in the developing forebrain. Genes Dev., 13, 3092-3105.
54. Hallonet, M., Hollemann, T., Pieler, T. and Gruss, P. (1999) Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system. Genes Dev., 13, 3106-3114.
55. Mui, S.H., Kim, J.W., Lemke, G. and Bertuzzi, S. (2005) Vax genes ventralize the embryonic eye. Genes Dev., 19, 1249-1259.
56. Macdonald, R., Barth, K.A., Xu, Q., Holder, N,, Mikkola, I. and Wilson, S.W. (1995) Midline signalling is required for Pax gene regulation and patterning of the eyes. Development, 121, 3267-3278.
57. Take-uchi, M., Clarke, J.D. and Wilson, S.W. (2003) Hedgehog signalling maintains the optic stalk-retinal interface through the regulation of Vax gene activity. Development, 130, 955-968.
58. Mi, H. and Barres, B.A. (1999) Purification and characterization of astrocyte precursor cells in the developing rat optic nerve. J. Neurosci., 19, 1049-1061.
59. Fuhrmann, S., Levine, E.M. and Reh, T.A. (2000) Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development, 127, 4599-4609.
60. Schwarz, M., Cecconi, F., Bernier, G., Andrejewski, N., Kammandel, B., Wagner, M. and Gruss, P. (2000) Spatial specification of mammalian eye territories by reciprocal transcriptional repression of Pax2 and Pax6. Development, 127, 4325-4334.
61. Martinez-Morales, J.R., Rodrigo, I. and Bovolenta, P. (2004) Eye development: A view from the retina pigmented epithelium. Bioessays, 26, 766-777.
62. Baumer, N., Marquardt, T., Stoykova, A., Spieler, D., Treichel, D., Ashery-Padan, R. and Gruss, P. (2003) Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6. Development, 130, 2903-2915.
63. Mochii, M., Mazaki, Y., Mizuno, N., Hayashi, H. and Eguchi, G. (1998) Role of Mitf in differentiation and transdifferentiation of chicken pigmented epithelial cell. Dev. Biol., 193, 47-62.
64. Nakayama, A., Nguyen, M.T., Chen, C.C., Opdecamp, K., Hodgkinson, C.A. and Arnheiter, H. (1998) Mutations in microphthalmia, the mouse homolog of the human deafness gene MITF, affect neuroepithelial and neural crest-derived melanocytes differently. Mech. Dev., 70, 155-166.
65. Smith, S.B., Zhou, B.K. and Orlow, S.J. (1998) Expression of tyrosinase and the tyrosinase related proteins in the Mitfvit (vitiligo) mouse eye: implications for the function of the microphthalmia transcription factor. Exp. Eye Res., 66, 403-410.
66. Martinez-Morales, J.R., Signore, M., Acampora, D., Simeone, A. and Bovolenta, P. (2001) Otx genes are required for tissue specification in the developing eye. Development, 128, 2019-2030.
67. Takeda, K., Yokoyama, S., Yasumoto, K., Saito, H., Udono, T., Takahashi, K. and Shibahara, S. (2003) OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium. Biochem. Biophys. Res. Commun., 300, 908-914.
68. Bovolenta, P., Mallamaci, A., Briata, P., Corte, G. and Boncinelli, E. (1997) Implication of OTX2 in pigment epithelium determination and neural retina differentiation. J. Neurosci., 17, 4243-4252.
69. Doward, W., Perveen, R., Lloyd, I.C., Ridgway, A.E., Wilson, L. and Black, G.C. (1999) A mutation in the RIEG1 gene associated with Peters' anomaly. J. Med. Genet., 36, 152-155.
70. Coulombre, A.J. and Coulombre, J.L. (1964) Lens development. I. Role of the lens in eye growth. J. Exp. Zool., 156, 39-47.
71. Genis-Galvez, J.M. (1966) Role of the lens in the morphogenesis of the iris and cornea. Nature, 210, 209-210.
72. Jamieson, R. V., Perveen, R., Kerr, B., Carette, M., Yardley, J., Heon, E., Wirth, M.G., van Heyningen, V., Donnai, D., Munier, F. et al. (2002) Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma. Hum. Mol. Genet., 11, 33-42.
73. Semina, E.V., Brownell, I., Mintz-Hittner, H.A., Murray, J.C. and Jamrich, M. (2001) Mutations in the human forkhead transcription factor FOXE3 associated with anterior segment ocular dysgenesis and cataracts. Hum. Mol. Genet., 10, 231-236.
74. Ormestad, M., Blixt, A., Churchill, A., Martinsson, T., Enerback, S. and Carlsson, P. (2002) Foxe3 haploinsufficiency in mice: A model for Peters' anomaly. Invest. Ophthalmol. Vis. Sci., 43, 1350-1357.
75. Semina, E.V., Ferrell, R.E., Mintz-Hittner, H.A., Bitoun, P., Alward, W.L., Reiter, R.S., Funkhauser, C., Daack-Hirsch, S. and Murray, J.C. (1998) A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat. Genet., 19, 167-170.
76. Seko, Y., Tanaka, Y. and Tokoro, T. (1994) Scleral cell growth is influenced by retinal pigment epithelium in vitro. Graefes Arch. Clin. Exp. Ophthalmol., 232, 545-552.
77. Sundin, O.H., Leppert, G.S., Silva, E.D., Yang, J.M., Dharmaraj, S., Maumenee, I.H., Santos, L.C., Parsa, C.F., Traboulsi, E.I., Broman, K.W. et al. (2005) Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein. Proc. Natl Acad. Sci. USA, 102, 9553-9558.
78. Uemura, A., Ogawa, M., Hirashima, M., Fujiwara, T., Koyama, S., Takagi, H., Honda, Y., Wiegand, S.J., Yancopoulos, G.D. and Nishikawa, S. (2002) Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. J. Clin. Invest., 110, 1619-1628.
79. Klinghoffer, R.A., Mueting-Nelsen, P.F., Faerman, A., Shani, M. and Soriano, P. (2001) The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions. Mol. Cell, 7, 343-354.
80. Dean, C., Ito, M., Makarenkova, H.P., Faber, S.C. and Lang, R.A. (2004) Bmp7 regulates branching morphogenesis of the lacrimal gland by promoting mesenchymal proliferation and condensation. Development, 131, 4155-4165.
81. Govindarajan, V., Ito, M., Makarenkova, H.P., Lang, R.A. and Overbeek, P.A. (2000) Endogenous and ectopic gland induction by FGF-10. Dev. Biol., 225, 188-200.
82. Makarenkova, H.P., Ito, M., Govindarajan, V., Faber, S.C., Sun, L., McMahon, G., Overbeek, P.A. and Lang, R.A. (2000) FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development, 127, 2563-2572.
83. Nguyen, M. and Arnheiter, H. (2000) Signaling and transcriptional regulation in early mammalian eye development: A link between FGF and MITF. Development, 127, 3581-3591.
84. Morgan, J.E. (2000) Optic nerve head structure in glaucoma: Astrocytes as mediators of axonal damage. Eye, 14, 437-444.
85. Neufeld, A.H. and Liu, B. (2003) Glaucomatous optic neuropathy: When glia misbehave. Neuroscientist, 9, 485-495.
86. Pena, J.D., Varela, H.J., Ricard, C.S. and Hernandez, M.R. (1999) Enhanced tenascin expression associated with reactive astrocytes in human optic nerve heads with primary open angle glaucoma. Exp. Eye Res., 68, 29-40.
87. Geijssen, H.C. and Greve, E.L. (1995) Vascular concepts in glaucoma. Curr. Opin. Ophthalmol., 6, 71-77.
88. Grieshaber, M.C. and Flammer, J. (2005) Blood flow in glaucoma. Curr. Opin. Ophthalmol., 16, 79-83.
89. Hayreh, S.S. (1994) Progress in the understanding of the vascular etiology of glaucoma. Curr. Opin. Ophthalmol., 5, 26-35.
90. Saint-Geniez, M. and D'Amore, P.A. (2004) Development and pathology of the hyaloid, choroidal and retinal vasculature. Int. J. Dev. Biol., 48, 1045-1058.
91. West, H., Richardson, W.D. and Fruttiger, M. (2005) Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes. Development, 132, 1855-1862.
92. Jiang, B., Liou, G.I., Behzadian, M.A. and Caldwell, R.B. (1994) Astrocytes modulate retinal vasculogenesis: Effects on fibronectin expression. J. Cell Sci., 107, 2499-2508.
93. Ikram, M.K., de Voogd, S., Wolfs, R.C., Hofman, A., Breteler, M.M., Hubbard, L.D. and de Jong, P.T. (2005) Retinal vessel diameters and incident open-angle glaucoma and optic disc changes: The Rotterdam study. Invest. Ophthalmol. Vis. Sci., 46, 1182-1187.
94. Mitchell, P., Leung, H., Wang, J.J., Rochtchina, E., Lee, A.J., Wong, T.Y. and Klein, R. (2005) Retinal vessel diameter and open-angle glaucoma: The Blue Mountains Eye Study. Ophthalmology, 112, 245-250.
95. Fantes, J., Ragge, N.K., Lynch, S.A., McGill, N.I., Collin, J.R., Howard-Peebles, P.N., Hayward, C., Vivian, A.J., Williamson, K., van Heyningen, V. et al. (2003) Mutations in SOX2 cause anophthalmia. Nat. Genet., 33, 461-463.
96. Gallardo, M.E., Lopez-Rios, J., Fernaud-Espinosa, I., Granadino, B., Sanz, R., Ramos, C., Ayuso, C., Seller, M.J., Brunner, H.G., Bovolenta, P. et al. (1999) 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.
97. Glaser, T., Jepeal, L., Edwards, J.G., Young, S.R., Favor, J. and Maas, R.L. (1994) PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat. Genet., 7, 463-471.
98. Voronina, V.A., Kozhemyakina, E.A., O'Kernick, C.M., Kahn, N.D., Wenger, S.L., Linberg, J.V., Schneider, A.S. and Mathers, P.H. (2004) Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea. Hum. Mol. Genet., 13, 315-322.
99. Ragge, N.K., Brown, A.G., Poloschek, C.M., Lorenz, B., Henderson, R.A., Clarke, M.P., Russell-Eggitt, I., Fielder, A., Gerrelli, D., Martinez-Barbera, J.P. et al. (2005) Heterozygous mutations of OTX2 cause severe ocular malformations. Am. J. Hum. Genet., 76, 1008-1022.
100. Grindley, J.C., Davidson, D.R. and Hill, R.E. (1995) The role of Pax-6 in eye and nasal development. Development, 121, 1433-1442.
101. Mathers, P.H., Grinberg, A., Mahon, K.A. and Jamrich, M. (1997) The Rx homeobox gene is essential for vertebrate eye development. Nature, 387, 603-607.
102. Jean, D., Bernier, G. and Gruss, P. (1999) 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.
103. Kamachi, Y., Uchikawa, M., Collignon, J., Lovell-Badge, R. and Kondoh, H. (1998) Involvement of Sox1, 2 and 3 in the early and subsequent molecular events of lens induction. Development, 125, 2521-2532.
104. Dattani, M.T., Martinez-Barbera, J.P., Thomas, P.Q., Brickman, J.M., Gupta, R., Martensson, I.L., Toresson, H., Fox, M., Wales, J.K., Hindmarsh, P.C. et al. (1998) Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat. Genet., 19, 125-133.
105. Cushman, L.J,, Burrows, H.L., Seasholtz, A.F., Lewandoski, M., Muzyczka, N. and Camper, S.A. (2000) Cre-mediated recombination in the pituitary gland. Genesis, 28, 167-174.
106. Crossley, P.H., Martinez, S., Ohkubo, Y. and Rubenstein, J.L. (2001) Coordinate expression of Fgf8, Otx2, Bmp4, and Shh in the rostral prosencephalon during development of the telencephalic and optic vesicles. Neuroscience, 108, 183-206.
107. Hodgkinson, C.A., Moore, K.J., Nakayama, A., Steingrimsson, E., Copeland, N.G., Jenkins, N.A. and Arnheiter, H. (1993) Mutations 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.
108. Echelard, Y., Epstein, D.J., St Jacques, B., Shen, L., Mohler, J., McMahon, J.A. and McMahon, A.P. (1993) Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell, 75, 1417-1430.
109. Cushman, L.J., Watkins-Chow, D.E., Brinkmeier, M.L., Raetzman, L.T., Radak, A.L., Lloyd, R.V. and Camper, S.A. (2001) Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility. Hum. Mol. Genet., 10, 1141-1153.