Signaling circuitries in development: Insights from the retinal determination gene network

Development

Volumn 132, Issue 1, 2005, Pages 3-13

  Silver, Serena J ^a,b,c   Rebay, Ilaria ^a,b  

^a WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; NOTCH RECEPTOR; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEIN;

CELL DIVISION; CELL PROLIFERATION; DROSOPHILA; EYE DEVELOPMENT; GENE FUNCTION; MOLECULAR INTERACTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; VERTEBRATE;

ANIMALS; DROSOPHILA; DROSOPHILA PROTEINS; GENE EXPRESSION REGULATION; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MODELS, BIOLOGICAL; PHENOTYPE; PHOTORECEPTORS, INVERTEBRATE; RECEPTOR, EPIDERMAL GROWTH FACTOR; RETINA; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEINS;

EID: 13444267769     PISSN: 09501991     EISSN: None     Source Type: Journal    
DOI: 10.1242/dev.01539     Document Type: Review

References (103)

1. Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M. et al. (1997). A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat. Genet. 15, 157-164.
2. Backman, M., Machon, O., van den Bout, C. J. and Krauss, S. (2003). Targeted disruption of mouse Dach1 results in postnatal lethality. Dev. Dyn. 226, 139-144.
3. Bai, J. and Montell, D. (2002). Eyes Absent, a key repressor of polar cell fate during Drosophila oogenesis. Development 129, 5377-5388.
4. Baonza, A. and Freeman, M. (2002). Control of Drosophila eye specification by Wingless signalling. Development 129, 5313-5322.
5. Bergmann, A., Tugentman, M., Shilo, B. Z. and Steller, H. (2002). Regulation of cell number by MAPK-dependent control of apoptosis. A mechanism for trophic survival signaling. Dev. Cell 2, 159-170.
6. Bessa, J., Gebelein, B., Pichaud, F., Casares, F. and Mann, R. S. (2002). Combinatorial control of Drosophila eye development by Eyeless, Homothorax, and Teashirt. Genes Dev. 16 2415-2427.
7. Bonini, N. M., Leiserson, W. M. and Benzer, S. (1993). The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 72, 379-395.
8. Bonini, N. M., Bui, Q. T., Gray-Board, G. L. and Warrick, J. M. (1997). The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 124, 4819-4826.
9. Bonini, N. M., Leiserson, W. M. and Benzer, S. (1998). Multiple roles of the eyes absent gene in Drosophila. Dev. Biol. 196, 42-57.
10. Boyle, M., Bonini, N. and DiNardo, S. (1997). Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm. Development 124, 971-982.
11. Bridges, C. B. (1935). The mutants and linkage data of chromosome four of Drosophila melanogaster. Z. Biol. 4, 401-420.
12. Burton, Q., Cole, L. K., Mulheisen, M., Chang, W. and Wu, D. K. (2004). The role of Pax2 in mouse inner ear development. Dev. Biol. 272, 161-175.
13. Callaerts, P., Leng, S., Clements, J., Benassayag, C., Cribbs, D., Kang, Y. Y., Walldorf, U., Fischbach, K. F. and Strauss, R. (2001). Drosophila Pax-6/eyeless is essential for normal adult brain structure and function. J. Neurobiol. 46, 73-88.
14. Carl, M., Loosli, F. and Wittbrodt, J. (2002). Six3 inactivation reveals its essential role for the formation and patterning of the vertebrate eye. Development 129, 4057-4063.
15. Chen, C. H., von Kessler, D. P., Park, W., Wang, B., Ma, Y. and Beachy, P. A. (1999a). Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell 98, 305-316.
16. Chen, R., Amoui, M., Zhang, Z. and Mardon, G. (1997). Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91, 893-903.
17. Chen, R., Halder, G., Zhang, Z. and Mardon, G. (1999b). Signaling by the TGF-beta homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila. Development 126, 935-943.
18. Cheyette, B. N., Green, P. J., Martin, K., Garren, H., Hartenstein, V. and 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, 977-996.
19. Coletta, R. D., Christensen, K., Reichenberger, K. J., Lamb, J., Micomonaco, D., Huang, L., Wolf, D. M., Muller-Tidow, C., Golub, T. R., Kawakami, K. et al. (2004). The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1. Proc. Natl. Acad. Sci. USA 101, 6478-6483.
20. Curtiss, J. and Mlodzik, M. (2000). Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent. Development 127, 1325-1336.
21. Czerny, T., Halder, G., Kloter, U., Souabni, A., Gehring, W. J. and Busslinger, M. (1999). twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol. Cell 3, 297-307.
22. Davis, R. J., Shen, W., Sandler, Y. I., Amoui, M., Purcell, P., Maas, R., Ou, C. N., Vogel, H., Beaudet, A. L. and Mardon, G. (2001a). Dach1 mutant mice bear no gross abnormalities in eye, limb, and brain development and exhibit postnatal lethality. Mol. Cell. Biol. 21, 1484-1490.
23. Davis, R. J., Shen, W., Sandler, Y. I., Heanue, T. A. and Mardon, G. (2001b). Characterization of mouse Dach2, a homologue of Drosophila dachshund. Mech. Dev. 102, 169-179.
24. Del Bene, F., Tessmar-Raible, K. and Wittbrodt, J. (2004). Direct interaction of geminin and Six3 in eye development. Nature 427, 745-749.
25. Dominguez, M., Ferres-Marco, D., Gutierrez-Avino, F. J., Speicher, S. A. and Beneyto, M. (2004). Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster. Nat. Genet. 36, 31-39.
26. Dozier, C., Kagoshima, H., Niklaus, G., Cassata, G. and Burglin, T. R. (2001). The Caenorhabditis elegans Six/sine oculis class homeobox gene ceh-32 is required for head morphogenesis. Dev. Biol. 236, 289-303.
27. Estrada, B., Casares, F. and Sanchez-Herrero, E. (2003). Development of the genitalia in Drosophila melanogaster. Differentiation 71, 299-310.
28. Fabrizio, J. J., Boyle, M. and DiNardo, S. (2003). A somatic role for eyes absent (eya) and sine oculis (so) in Drosophila spermatocyte development. Dev. Biol. 258, 117-128.
29. Fisher, A. L. and Caudy, M. (1998). Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates. Genes Dev. 12, 1931-1940.
30. Ford, H. L., Kabingu, E. N., Bump, E. A., Mutter, G. L. and Pardee, A. B. (1998). Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: a possible mechanism of breast carcinogenesis. Proc. Natl. Acad. Sci. USA 95, 12608-12613.
31. 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.
32. Halder, G., Callaerts, P., Flister, S., Walldorf, U., Kloter, U. and Gehring, W. J. (1998). Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125, 2181-2191.
33. Hanson, I. M., Fletcher, J. M., Jordan, T., Brown, A., Taylor, D., Adams, R. J., Punnett, H. H. and van Heyningen, V. (1994 . Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nat. Genet. 6, 168-173.
34. Hazelett, D. J., Bourouis, M., Walldorf, U. and 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.
35. Heanue, T. A., Reshef, R., Davis, R. J., Mardon, G., Oliver, G., Tomarev, S., Lassar, A. B. and Tabin, C. J. (1999). Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes Dev. 13, 3231-3243.
36. Hsiao, F. C., Williams, A., Davies, E. L. and Rebay, I. (2001). Eyes absent mediates cross-talk between retinal determination genes and the receptor tyrosine kinase signaling pathway. Dev. Cell 1, 51-61.
37. Ikeda, K., Watanabe, Y., Ohto, H. and Kawakami, K. (2002). Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol. Cell. Biol. 22, 6759-6766.
38. Jang, C. C., Chao, J. L., Jones, N., Yao, L. C., Bessarab, D. A., Kuo, Y. M., Jun, S., Desplan, C., Beckendorf, S. K. and Sun, Y. H. (2003). Two Pax genes, eye gone and eyeless, act cooperatively in promoting Drosophila eye development. Development 130, 2939-2951.
39. Jun, S., Wallen, R. V., Goriely, A., Kalionis, B. and Desplan, C. (1998). Lune/eye gone, a Pax-like protein, uses a partial paired domain and a homeodomain for DNA recognition. Proc. Natl. Acad. Sci. USA 95, 13720-13725.
40. Kammermeier, L., Leemans, R., Hirth, F., Flister, S., Wenger, U., Walldorf, U., Gehring, W. J. and Reichert, H. (2001). Differential expression and function of the Drosophila Pax6 genes eyeless and twin of eyeless in embryonic central nervous system development. Mech. Dev. 103, 71-78.
41. Kardon, G., Heanue, T. A. and Tabin, C. J. (2002). Pax3 and Dach2 positive regulation in the developing somite. Dev. Dyn. 224, 350-355.
42. Kawakami, K., Sato, S., Ozaki, H. and Ikeda, K. (2000). Six family genes-structure and function as transcription factors and their roles in development. Bioessays 22, 616-626.
43. Keisman, E. L. and Baker, B. S. (2001). The Drosophila sex determination hierarchy modulates wingless and decapentaplegic signaling to deploy dachshund sex-specifically in the genital imaginal disc. Development 128, 1643-1656.
44. Kenyon, K. L., Ranade, S. S., Curtiss, J., Mlodzik, M. and Pignoni, F. (2003). Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head. Dev. Cell 5, 403-414.
45. Kim, S. S., Zhang, R., Braunstein, S. E., Joachimiak, A., Cvekl, A. and Hegde, R. S. (2002). Structure of the retinal determination protein dachshund reveals a DNA binding motif. Structure 10, 787-795.
46. Kirby, R. J., Hamilton, G. M., Finnegan, D. J., Johnson, K. J. and Jarman, A. P (2001). Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development. Curr. Biol. 11, 1044-1049.
47. Klesert, T. R., Cho, D. H., Clark, J. I., Maylie, J., Adelman, J., Snider, L., Yuen, E. C., Soriano, P. and Tapscott, S. J. (2000). Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy. Nat. Genet. 25, 105-109.
48. Kobayashi, M., Nishikawa, K., Suzuki, T. and Yamamoto, M. (2001). The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation. Dev. Biol. 232, 315-326.
49. Kozmik, Z., Pfeffer, P., Kralova, J., Paces, J., Paces, V., Kalousova, A. and Cvekl, A. (1999). Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene. Dev. Genes Evol. 209, 537-545.
50. Kronhamn, J., Frei, E., Daube, M., Jiao, R., Shi, Y., Noll, M. and Rasmuson-Lestander, A. (2002). Headless flies produced by mutations in the paralogous Pax6 genes eyeless and twin of eyeless. Development 129, 1015-1026.
51. Kumar, P. and Moses, K. (2001). EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. Cell 104, 687-697.
52. Laclef, C., Hamard, G., Demignon, J., Souil, E., Houbron, C. and Maire, P. (2003). Altered myogenesis in Six1-deficient mice. Development 130, 2239-2252.
53. Li, X., Perissi, V., Liu, F., Rose, D. W. and Rosenfeld, M. G. (2002). Tissue-specific regulation of retinal and pituitary precursor cell proliferation. Science 297, 1180-1183.
54. Li, X., Oghi, K. A., Zhang, J., Krones, A., Bush, K. T., Glass, C. K., Nigam, S. K., Aggarwal, A. K., Maas, R., Rose, D. W. et al. (2003). Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature 426 247-254.
55. Lopez-Rios, J., Tessmar, K., Loosli, F., Wittbrodt, J. and Bovolenta, P. (2003). Six3 and Six6 activity is modulated by members of the groucho family. Development 130, 185-195.
56. Ma, C. and 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, 2279-2289.
57. Mardon, G., Solomon, N. M. and Rubin, G. M. (1994). dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development 120, 3473-3486.
58. Mikkola, I., Bruun, J. A., Bjorkoy, G., Holm, T. and Johansen, T. (1999). Phosphorylation of the transactivation domain of Pax6 by extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. J. Biol. Chem. 274, 15115-15126.
59. Ohto, H., Kamada, S., Tago, K., Tominaga, S.-I., Ozaki, H., Sato, S. and Kawakami, K. (1999). Cooperation of Six and Eya in activation of their target genes through nuclear translocation of Eya. Mol. Cell. Biol. 19, 6815-6824.
60. Ozaki, H., Watanabe, Y., Takahashi, K., Kitamura, K., Tanaka, A., Urase, K., Momoi, T., Sudo, K., Sakagami, J., Asano, M. et al. (2001). Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development. Mol. Cell. Biol. 21, 3343-3350.
61. Ozaki, H., Nakamura, K., Funahashi, J., Ikeda, K., Yamada, G., Tokano, H., Okamura, H. O., Kitamura, K., Muto, S., Kotaki, H. et al. (2004). Six1 controls patterning of the mouse otic vesicle. Development 131, 551-562.
62. Pappu, K. and Mardon, G. (2002). Retinal specification and determination in Drosophila. In Drosophila Eye Development (ed. K. Moses), pp. 5-17. Berlin, Germany: Springer-Verlag.
63. Pappu, K. S., Chen, R., Middlebrooks, B. W., Woo, C., Heberlein, U. and Mardon, G. (2003). Mechanism of hedgehog signaling during Drosophila eye development. Development 130, 3053-3062.
64. Parker, M. H., Seale, P. and Rudnicki, M. A. (2003). Looking back to the embryo: defining transcriptional networks in adult myogenesis. Nat. Rev. Genet. 4, 497-507.
65. Pasquier, L., Dubourg, C., Blayau, M., Lazaro, L., le Marec, B., David, V. and Odent, S. (2000). A new mutation in the six-domain of SIX3 gene causes holoprosencephaly. Eur. J. Hum. Genet. 8, 797-800.
66. Petropoulos, H. and Skerjanc, I. S. (2002). Beta-catenin is essential and sufficient for skeletal myogenesis in P19 cells. J. Biol. Chem. 277, 15393-15399.
67. Petropoulos, H., Gianakopoulos, P. J., Ridgeway, A. G. and Skerjanc, I. S. (2004). Disruption of Meox or Gli activity ablates skeletal myogenesis in P19 cells. J. Biol. Chem. 279, 23874-23881.
68. Pignoni, F., Hu, B., Zavitz, K. H., Xiao, J., Garrity, P. A. and Zipursky, S. L. (1997). The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 91, 881-891.
69. Punzo, C., Seimiya, M., Flister, S., Gehring, W. J. and Plaza, S. (2002). Differential interactions of eyeless and twin of eyeless with the sine oculis enhancer. Development 129, 625-634.
70. Quiring, R., Walldorf, U., Kloter, U. and Gehring, W. J. (1994). Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265, 785-789.
71. Rayapureddi, J. P., Kattamuri, C., Steinmetz, B. D., Frankfort, B. J., Ostrin, E. J., Mardon, G. and Hegde, R. S. (2003). Eyes absent represents a class of protein tyrosine phosphatases. Nature 426, 295-298.
72. Rebay, I., Chen, F., Hsiao, F., Kolodziej, P. A., Kuang, B. H., Laverty, T., Suh, C., Voas, M., Williams, A. and Rubin, G. M. (2000). A genetic screen for novel components of the Ras/Mitogen-activated protein kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein. Genetics 154, 695-712.
73. Ridgeway, A. G. and Skerjanc, I. S. (2001). Pax3 is essential for skeletal myogenesis and the expression of six1 and eya2. J. Biol. Chem. 276, 19033-19039.
74. Riley, B. B. and Phillips, B. T. (2003). Ringing in the new ear: resolution of cell interactions in otic development. Dev. Biol. 261, 289-312.
75. Rodrigues, A. B. and Moses, K. (2004). Growth and specification: fly Pax6 homologs eyegone and eyeless have distinct functions. Bioessays 26, 600-603.
76. Royet, J. and Finkelstein, R. (1997). Establishing primordia in the Drosophila eye-antennal imaginal disc: the roles of decapentaplegic, wingless and hedgehog. Development 124, 4793-4800.
77. Ruf, R. G., Xu, P. X., Silvius, D., Otto, E. A., Beekmann, F., Muerb, U. T., Kumar, S., Neuhaus, T. J., Kemper, M. J., Raymond, R. M., Jr et al. (2004). SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc. Natl. Acad. Sci. USA 101, 8090-8095.
78. Sanchez, L., Gorfinkiel, N. and Guerrero, I. (2001). Sex determination genes control the development of the Drosophila genital disc, modulating the response to Hedgehog, Wingless and Decapentaplegic signals. Development 128, 1033-1043.
79. Seimiya, M. and Gehring, W. J. (2000). The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism. Development 127, 1879-1886.
80. Seo, H. C., Curtiss, J., Mlodzik, M. and Fjose, A. (1999). Six class homeobox genes in drosophila belong to three distinct families and are involved in head development. Mech. Dev. 83, 127-139.
81. Shen, W. and Mardon, G. (1997). Ectopic eye development in Drosophila induced by directed dachshund expression. Development 124, 45-52.
82. Silver, S. J., Davies, E. L., Doyon, L. and Rebay, I. (2003). Functional dissection of eyes absent reveals new modes of regulation within the retinal determination gene network. Mol. Cell. Biol. 23, 5989-5999.
83. Spitz, F., Demignon, J., Porteu, A., Kahn, A., Concordet, J. P., Daegelen, D. and Maire, P. (1998). Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site. Proc. Natl. Acad. Sci. USA 95, 14220-14225.
84. Spradling, A. C. (1993). Developmental genetics of oogenesis. In The Development of Drosophila melanogaster, Vol. 1 (ed. M. Bate and A. M. Arias), pp. 1-70. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
85. Tavsanli, B. C., Ostrin, E. J., Burgess, H. K., Middlebrooks, B. W., Pham, T. A. and Mardon, G. (2004). Structure-function analysis of the Drosophila retinal determination protein Dachshund. Dev. Biol. 272, 231-247.
86. Tootle, T. L., Silver, S. J., Davies, E. L., Newman, V., Latek, R. R., Mills, I. A., Selengut, J. D., Parlikar, B. E. and Rebay, I. (2003). The transcription factor Eyes absent is a protein tyrosine phosphatase. Nature 426, 299-302.
87. Torres, M., Gomez-Pardo, E. and Gruss, P. (1996). Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122, 3381-3391.
88. Treisman, J. E. and Heberlein, U. (1998). Eye development in Drosophila: formation of the eye field and control of differentiation. Curr. Top. Dev. Biol. 39, 119-158.
89. Treisman, J. E. and Rubin, G. M. (1995). wingless inhibits morphogenesic furrow movement in the Drosophila eye disc. Development 121, 3519-3527.
90. Voas, M. G. and Rebay, I. (2004). Signal integration during development: insights from the Drosophila eye. Dev. Dyn. 229, 162-175.
91. Wallis, D. E., Roessler, E., Hehr, U., Nanni, L., Wiltshire, T., Richieri-Costa, A., Gillessen-Kaesbach, G., Zackai, E. H., Rommens, J. and Muenke, M. (1999). Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. Nat. Genet. 22, 196-198.
92. Wansink, D. G. and Wieringa, B. (2003). Transgenic mouse models for myotonic dystrophy type 1 (DM1). Cytogenet. Genome Res. 100, 230-242.
93. Wayne, S., Robertson, N. G., DeClau, F., Chen, N., Verhoeven, K., Prasad, S., Tranebjarg, L., Morton, C. C., Ryan, A. F., van Camp, G. et al. (2001). Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum. Mol. Genet. 10, 195-200.
94. Widmann, C., Gibson, S., Jarpe, M. B. and Johnson, G. L. (1999). Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol. Rev. 79, 143-180.
95. Xu, P. X., Cheng, J., Epstein, J. A. and Maas, R. L. (1997a). Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function. Proc. Natl. Acad. Sci. USA 94, 11974-11979.
96. Xu, P. X., Woo, I., Her, H., Beier, D. R. and Maas, R. L. (1997b). Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode. Development 124, 219-231.
97. Xu, P. X., Adams, J., Peters, H., Brown, M. C., Heaney, S. and Maas, R. (1999). Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat. Genet. 23, 113-117.
98. Xu, P. X., Zheng, W., Laclef, C., Maire, P., Maas, R. L., Peters, H. and Xu, X. (2002). Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid. Development 129 3033-3044.
99. Xu, P. X., Zheng, W., Huang, L., Maire, P., Laclef, C. and Silvius, D. (2003). Six1 is required for the early organogenesis of mammalian kidney. Development 130, 3085-3094.
100. Yu, Y., Khan, J., Khanna, C., Helman, L., Meltzer, P. S. and Merlino, G. (2004). Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat. Med. 10, 175-181.
101. Zheng, W., Huang, L., Wei, Z. B., Silvius, D., Tang, B. and Xu, P. X. (2003). The role of Six1 in mammalian auditory system development. Development 130, 3989-4000.
102. Zhu, C. C., Dyer, M. A., Uchikawa, M., Kondoh, H., Lagutin, O. V. and Oliver, G. (2002). Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. Development 129, 2835-2849.
103. Zimmerman, J. E., Bui, Q. T., Steingrimsson, E., Nagle, D. L., Fu, W., Genin, A., Spinner, N. B., Copeland, N. G., Jenkins, N. A., Bucan, M. et al. (1997). Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. Genome Res. 7, 128-141.