title: Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells.
abstract: 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 RXRalpha/RARbeta and RXRalpha/RARgamma. 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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC Collège de France, BP10142, 67404 Illkirch Cedex, CU de Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Matt
authors.forename: Valérie
authors.initials: V
authors.lastname: Dupé
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Garnier
authors.forename: Christine
authors.initials: C
authors.lastname: Dennefeld
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Manuel
authors.initials: M
authors.lastname: Mark
authors.forename: Norbert B
authors.initials: NB
authors.lastname: Ghyselinck
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000502:physiology; D000818:Animals; D047108:Embryonic Development; D005123:Eye / Q000196:embryology* / Q000254:growth & development; D008648:Mesoderm; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000187:drug effects*; D009432:Neural Crest / Q000166:cytology*; D019899:Paracrine Communication; D018168:Receptors, Retinoic Acid / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases