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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.
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