Impairing retinoic acid signalling in the neural crest cells is sufficient to alter entire eye morphogenesis.
Retinoic acid (RA) is known to be required at various levels of eye patterning via Retinoic Acid Receptors (RAR); however the molecular and cellular mechanisms triggered by these nuclear receptors are still obscure. The genetic studies performed here enable us to present a new model to study RA action during eye development. By inactivating the three RARs, specifically in the periocular mesenchyme, we discriminate the individual contribution of each RAR during eye development and describe a new function for RARs during the formation of the optic nerve. We demonstrate that RARalpha is the only receptor that mediates RA signalling in the neurectoderm during ocular development. Surprisingly, and despite a sophisticated pattern of RA-activity in the developing retina, we observed that RA signalling is not autonomously required in this tissue for eye formation. We show that the action of RA during eye morphogenesis is occurring specifically in neural crest-derived periocular mesenchyme and is mediated by all three RARs. Furthermore, we point out that Pitx2, which encodes a homeodomain transcription factor, is a key RA-responsive gene in neural crest cells during eye development. Interestingly, we observed that RA is required in the neural crest cells for normal position of the extraocular muscle.
Matt
Nicolas
N
UPR9022 du CNRS, IBMC, 15 rues Descartes, 67084 Strasbourg, France.
Ghyselinck
Norbert B
NB
Pellerin
Isabelle
I
Dupé
Valérie
V
D000818:Animals; D019521:Body Patterning; D004622:Embryo, Mammalian / Q000002:abnormalities; D005123:Eye / Q000196:embryology* / Q000473:pathology; D005124:Eye Abnormalities / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009132:Muscles / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000378:metabolism* / Q000473:pathology; D009900:Optic Nerve / Q000196:embryology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D000097577:Homeobox Protein PITX2; D000097768:Retinoic Acid Receptor gamma
D018398:Homeodomain Proteins; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D014212:Tretinoin; D000097577:Homeobox Protein PITX2; D000097768:Retinoic Acid Receptor gamma; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta