Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF

During vertebrate eye development, the optic vesicle is partitioned into a domain at its distal tip that will give rise to the neuroretina, and anothe r at its proximal base that will give rise to the pigmented epithelium. Bot h domains are initially bipotential, each capable of giving rise to either neuroretina or pigmented epithelium, The partitioning depends on extrinsic signals, notably fibroblast growth factors, which emanate from the overlyin g surface ectoderm and induce the adjacent neuroepithelium to assume the ne uroretinal fate, Using explant cultures of mouse optic vesicles, we demonst rate that bipotentiality of the optic neuroepithelium is associated with th e initial coexpression of the basic-helix-loop-helix-zipper transcription f actor MITF, which is later needed solely in the pigmented epithelium, and a set of distinct transcription factors that become restricted to the neuror etina. Implantation of fibroblast growth factor-coated beads close to the b ase of the optic vesicle leads to a rapid downregulation of MITF and the de velopment of an epithelium that, by morphology, gene expression, and lack o f pigmentation, resembles the future neuroretina. Conversely, the removal o f the surface ectoderm results in the maintenance of MITF in the distal opt ic epithelium, lack of expression of the neuroretinal-specific CHX10 transc ription factor, and conversion of this epithelium into a pigmented monolaye r, This phenomenon can be prevented by the application of fibroblast growth factor alone. In Mitf mutant embryos, parts of the future pigment epitheli um become thickened, lose expression of a number of pigment epithelium tran scription factors, gain expression of neuroretinal transcription factors, a nd eventually transdifferentiate into a laminated second retina. The result s support the view that the bipotential optic neuroepithelium is characteri zed by overlapping gene expression patterns and that selective gene repress ion, brought about by local extrinsic signals, leads to the separation into discrete expression domains and, hence, to domain specification.