|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
1 Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain
2 MRC Centre for Developmental Neurobiology, New Hunt’s House, 4th Floor, King’s College London, Guy’s Campus, London Bridge, London SE11 9RT, UK
3 International Institute of Genetics and Biophysics, CNR, Via Marconi, 12, 80125 Naples, Italy
*Author for correspondence (e-mail: bovolenta{at}cajal.csic.es)
Accepted March 19, 2001
Patterning of the vertebrate eye appears to be controlled by the mutual regulation and the progressive restriction of the expression domains of a number of genes initially co-expressed within the eye anlage. Previous data suggest that both Otx1 and Otx2 might contribute to the establishment of the different eye territories. Here, we have analysed the ocular phenotype of mice carrying different functional copies of Otx1 and Otx2 and we show that these genes are required in a dose-dependent manner for the normal development of the eye. Thus, all Otx1-/-; Otx2+/- and 30% of Otx1+/-; Otx2+/- genotypes presented consistent and profound ocular malformation, including lens, pigment epithelium, neural retina and optic stalk defects. During embryonic development, optic vesicle infolding was severely altered and the expression of pigment epithelium-specific genes, such as Mitf or tyrosinase, was lost. Lack of pigment epithelium specification was associated with an expansion of the prospective neural retina and optic stalk territories, as determined by the expression of Pax6, Six3 and Pax2. Later in development the presumptive pigment epithelium region acquired features of mature neural retina, including the generation of Islet1-positive neurones. Furthermore, in Otx1-/-; Otx2+/- mice neural retina cell proliferation, cell differentiation and apoptotic cell death were also severely affected. Based on these findings we propose a model in which Otx gene products are required for the determination and differentiation of the pigment epithelium, co-operating with other eye patterning genes in the determination of the specialised tissues that will constitute the mature vertebrate eye.
Key words: Otx1, Otx2,, Eye, Pigment epithelium, Optic vesicle patterning, Mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Vopalensky and Z. Kozmik Eye evolution: common use and independent recruitment of genetic components Phil Trans R Soc B, October 12, 2009; 364(1531): 2819 - 2832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Westenskow, S. Piccolo, and S. Fuhrmann {beta}-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression Development, August 1, 2009; 136(15): 2505 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishii, K. Weinberg, I. Oda-Ishii, L. Coughlin, and T. Mikawa Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes Development, August 1, 2009; 136(15): 2579 - 2589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Esumi, S. Kachi, L. Hackler Jr, T. Masuda, Z. Yang, P. A. Campochiaro, and D. J. Zack BEST1 expression in the retinal pigment epithelium is modulated by OTX family members Hum. Mol. Genet., January 1, 2009; 18(1): 128 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ogino, M. Fisher, and R. M. Grainger Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification Development, January 15, 2008; 135(2): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Koike, A. Nishida, S. Ueno, H. Saito, R. Sanuki, S. Sato, A. Furukawa, S. Aizawa, I. Matsuo, N. Suzuki, et al. Functional Roles of Otx2 Transcription Factor in Postnatal Mouse Retinal Development Mol. Cell. Biol., December 1, 2007; 27(23): 8318 - 8329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Muller, H. Rohrer, and A. Vogel-Hopker Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo Development, October 1, 2007; 134(19): 3483 - 3493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xu, P. D. Witmer, S. Lumayag, B. Kovacs, and D. Valle MicroRNA (miRNA) Transcriptome of Mouse Retina and Identification of a Sensory Organ-specific miRNA Cluster J. Biol. Chem., August 24, 2007; 282(34): 25053 - 25066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, S. Thurig, O. Mohamed, D. Dufort, and V. A. Wallace Mapping Canonical Wnt Signaling in the Developing and Adult Retina Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5088 - 5097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Morcillo, J. R. Martinez-Morales, F. Trousse, Y. Fermin, J. C. Sowden, and P. Bovolenta Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH Development, August 15, 2006; 133(16): 3179 - 3190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Puelles, D. Acampora, R. Gogoi, F. Tuorto, A. Papalia, F. Guillemot, S.-L. Ang, and A. Simeone Otx2 controls identity and fate of glutamatergic progenitors of the thalamus by repressing GABAergic differentiation. J. Neurosci., May 31, 2006; 26(22): 5955 - 5964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Zhang, Y. Zou, R. T. Yu, F. H. Gage, and R. M. Evans Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1. Genes & Dev., May 15, 2006; 20(10): 1308 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Foucher, M. Mione, A. Simeone, D. Acampora, L. Bally-Cuif, and C. Houart Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants Development, May 15, 2006; 133(10): 1891 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Yaron, C. Farhy, T. Marquardt, M. Applebury, and R. Ashery-Padan Notch1 functions to suppress cone-photoreceptor fate specification in the developing mouse retina Development, April 1, 2006; 133(7): 1367 - 1378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Evans and P. J. Gage Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development Hum. Mol. Genet., November 15, 2005; 14(22): 3347 - 3359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Alfano, C. Vitiello, C. Caccioppoli, T. Caramico, A. Carola, M. J. Szego, R. R. McInnes, A. Auricchio, and S. Banfi Natural antisense transcripts associated with genes involved in eye development Hum. Mol. Genet., April 1, 2005; 14(7): 913 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Horsford, M.-T. T. Nguyen, G. C. Sellar, R. Kothary, H. Arnheiter, and R. R. McInnes Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity Development, January 1, 2005; 132(1): 177 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Aijaz, B. J. Clark, K. Williamson, V. van Heyningen, D. Morrison, D. FitzPatrick, R. Collin, N. Ragge, A. Christoforou, A. Brown, et al. Absence of SIX6 Mutations in Microphthalmia, Anophthalmia, and Coloboma Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 3871 - 3876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rowan, C.-M. A. Chen, T. L. Young, D. E. Fisher, and C. L. Cepko Transdifferentiation of the retina into pigmented cells in ocular retardation mice defines a new function of the homeodomain gene Chx10 Development, October 15, 2004; 131(20): 5139 - 5152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Planque, G. Raposo, L. Leconte, O. Anezo, P. Martin, and S. Saule Microphthalmia Transcription Factor Induces Both Retinal Pigmented Epithelium and Neural Crest Melanocytes from Neuroretina Cells J. Biol. Chem., October 1, 2004; 279(40): 41911 - 41917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Treisman How to make an eye Development, August 15, 2004; 131(16): 3823 - 3827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kimura-Yoshida, K. Kitajima, I. Oda-Ishii, E Tian, M. Suzuki, M. Yamamoto, T. Suzuki, M. Kobayashi, S. Aizawa, and I. Matsuo Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for vertebrate head specification Development, January 1, 2004; 131(1): 57 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Baumer, T. Marquardt, A. Stoykova, D. Spieler, D. Treichel, R. Ashery-Padan, and P. Gruss Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6 Development, July 1, 2003; 130(13): 2903 - 2915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Martinez-Morales, V. Dolez, I. Rodrigo, R. Zaccarini, L. Leconte, P. Bovolenta, and S. Saule OTX2 Activates the Molecular Network Underlying Retina Pigment Epithelium Differentiation J. Biol. Chem., June 6, 2003; 278(24): 21721 - 21731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Wu, M. Li, D. R. Hinton, L. Guo, S. Jiang, J. T. Wang, A. Zeng, J. B. Xie, M. Snead, C. Shuler, et al. Microphthalmia Resulting from Msx2-Induced Apoptosis in the Optic Vesicle Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2404 - 2412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Perron, S. Boy, M. A. Amato, A. Viczian, K. Koebernick, T. Pieler, and W. A. Harris A novel function for Hedgehog signalling in retinal pigment epithelium differentiation Development, April 15, 2003; 130(8): 1565 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Viczian, R. Vignali, M. E. Zuber, G. Barsacchi, and W. A. Harris XOtx5b and XOtx2 regulate photoreceptor and bipolar fates in the Xenopus retina Development, April 1, 2003; 130(7): 1281 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Li, X. Zhu, B. Brown, and C. M. Craft Gene Expression Networks Underlying Retinoic Acid-Induced Differentiation of Human Retinoblastoma Cells Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 996 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhao, Q. Chen, F.-C. Hung, and P. A. Overbeek BMP signaling is required for development of the ciliary body Development, January 10, 2002; 129(19): 4435 - 4442. [Abstract] [Full Text] [PDF]
|
|
