Fig. 7.
Model for cross-talk between RA and Wnt signaling during eye morphogenesis. Our findings demonstrate that RA synthesized by the dorsal (Raldh1) or ventral (Raldh3) retina is secreted and acts directly with nuclear RA receptors to induce Pitx2 in the perioptic mesenchyme; elimination of both enzymes is necessary to observe ocular defects as RA generated by either Raldh1 or Raldh3 can provide RA to both dorsal and ventral perioptic mesenchyme (Molotkov et al., 2006). Our model further suggests that a major downstream target of RA-induced Pitx2 is Dkk2 whose induction in the perioptic mesenchyme antagonizes Wnt/β-catenin signaling to allow proper morphogenesis of the perioptic mesenchyme, eyelids, and cornea. el, eyelid fold; le, lens; pm, perioptic mesenchyme; RA, retinoic acid.