RT Journal Article
SR Electronic
T1 Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells
JF Development
JO Development
FD The Company of Biologists Limited
SP 4789
OP 4800
DO 10.1242/dev.02031
VO 132
IS 21
A1 Matt, Nicolas
A1 Dupé, Valérie
A1 Garnier, Jean-Marie
A1 Dennefeld, Christine
A1 Chambon, Pierre
A1 Mark, Manuel
A1 Ghyselinck, Norbert B.
YR 2005
UL http://dev.biologists.org/content/132/21/4789.abstract
AB Using genetic approaches in the mouse, we show that the primary target tissue of retinoic acid (RA) action during eye morphogenesis is not the retina nor the corneal ectoderm, which both express RA-synthesizing retinaldehyde dehydrogenases (RALDH1 and RALDH3), but the neural crest cell-derived periocular mesenchyme (POM), which is devoid of RALDH. In POM, the effects of the paracrine RA signal are mediated by the nuclear RA receptors heterodimers RXRα/RARβ and RXRα/RARγ. These heterodimers appear to control: (1) the remodeling of the POM through activation of Eya2-related apoptosis; (2) the expression of Foxc1 and Pitx2, which play crucial roles in anterior eye segment development; and (3) the growth of the ventral retina. We additionally show that RALDH1 and RALDH3 are the only enzymes that are required for RA synthesis in the eye region from E10.5 to E13.5, and that patterning of the dorsoventral axis of the retina does not require RA.