Fig. 10. RA-dependent eye morphogenesis is orchestrated by the NCC-derived
periocular mesenchyme. RALDH1 (red) and RALDH3 (orange), expressed in the
retina, the retinal-pigmented epithelium, the lens and the corneal ectoderm,
are the only RA-synthesizing enzymes required in the eye region from E10.5
onwards. The RA synthesized in these locations (yellow arrows) diffuses
towards the periocular mesenchyme (POM, blue), where it determines eye
morphogenesis through the activation of RXR
/RARß and
RXR
/RAR
heterodimers. The latter may control (1) the
Eya2-dependent apoptosis involved in POM remodeling; (2) the
expression of Foxc1 and Pitx2 transcription factors that are
required for the eye anterior segment morphogenesis; and (3) the production of
an unknown signal (question mark) necessary for the growth of the ventral
retina. Asterisk indicates the RA-depleted zone expressing the catabolizing
enzymes CYP26A1 and CYP26C1. This drawing is representative of the E11.5
condition.