Fig. 8. Proposed model for the regulation of the RPE and NR domain in the developing chick eye. (A) The RPE is specified first at stage 9. BMP genes expressed in the surface ectoderm at stage 8 (e.g. Bmp4 and Bmp7) induce Mitf expression in the underlying optic vesicle. Mitf expression is strongest in the region of the optic vesicle that directly contacts the overlying ectoderm. (B) At stage 10, NR specification is initiated by signals released from the FGF-expressing surface ectoderm. FGF-mediated (e.g. FGF1, 2 and 19) induction of Chx10 in the distal portion of the optic vesicle inhibits Mitf and Otx2 expression in this region, which results in the subdivision of the optic vesicle into a RPE and NR domain. (C) At early optic cup stages, Mitf expression is still maintained in the presumptive RPE by BMPs expressed within the RPE itself and in the surrounding mesenchyme (e.g. BMP5, BMP7). At these stages, BMP family members expressed in the dorsal surface ectoderm and adjacent diencephalon could also be emanating into the underlying mesenchyme to maintain Mitf expression and hence RPE development. On the other hand, FGFs present in the NR itself (e.g. FGF3, 8, 15 and 19) maintain Chx10 expression, which allows NR development in the adjacent inner layer of the optic cup. The antagonistic interaction between BMPs/MITF within the RPE and FGFs/CHX10 within the NR ensures the development of the vertebrate eye at early optic cup stages.