Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity

DJ Horsford, MTT Nguyen, GC Sellar, R Kothary… - 2005 - journals.biologists.com
DJ Horsford, MTT Nguyen, GC Sellar, R Kothary, H Arnheiter, RR McInnes
2005journals.biologists.com
During vertebrate eye development, the cells of the optic vesicle (OV) become either
neuroretinal progenitors expressing the transcription factor Chx10, or retinal pigment
epithelium (RPE) progenitors expressing the transcription factor Mitf. Chx10 mutations lead
to microphthalmia and impaired neuroretinal proliferation. Mitf mutants have a dorsal RPE-to-
neuroretinal phenotypic transformation, indicating that Mitf is a determinant of RPE identity.
We report here that Mitf is expressed ectopically in the Chx10or-J/or-J neuroretina (NR) …
During vertebrate eye development, the cells of the optic vesicle (OV)become either neuroretinal progenitors expressing the transcription factor Chx10, or retinal pigment epithelium (RPE) progenitors expressing the transcription factor Mitf. Chx10 mutations lead to microphthalmia and impaired neuroretinal proliferation. Mitf mutants have a dorsal RPE-to-neuroretinal phenotypic transformation, indicating that Mitfis a determinant of RPE identity. We report here that Mitf is expressed ectopically in the Chx10or-J/or-J neuroretina(NR), demonstrating that Chx10 normally represses the neuroretinal expression of Mitf. The ectopic expression of Mitf in the Chx10or-J/or-J NR deflects it towards an RPE-like identity; this phenotype results not from a failure of neuroretinal specification, but from a partial loss of neuroretinal maintenance. Using Chx10 and Mitf transgenic and mutant mice, we have identified an antagonistic interaction between Chx10 and Mitf in regulating retinal cell identity. FGF (fibroblast growth factor) exposure in a developing OV has also been shown to repress Mitf expression. We demonstrate that the repression of Mitfby FGF is Chx10 dependent, indicating that FGF, Chx10 and Mitf are components of a pathway that determines and maintains the identity of the NR.
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