RETINOIDS AND THEIR RECEPTORS IN SKELETAL DEVELOPMENT

The embryonic vertebrate limb serves as an excellent experimental mode l system in which to study mechanisms that regulate morphogenesis of t he skeleton. The appendicular skeleton arises through the process of e ndochondral ossification, whereby a cartilage template is initially fo rmed and subsequently replaced by bone. One molecule that has a dramat ic effect on these processes is the vitamin-A metabolite, retinoic aci d (RA). RA functions through a class of nuclear hormone receptors, the retinoic acid receptors (RARs) and retinoid-X-receptors (RXRs), to re gulate gene transcription. Experimental evidence from RA teratogenesis suggests that the presence of ligand-activated RARs and/or inappropri ate expression of RARs inhibits chondrogenesis. Conversely, genetic an alysis has shown that the absence of the receptors can lead to deficie ncies in cartilage formation while also promoting chondrogenesis at ec topic sites. Taken together, these studies suggest that the RARs play a fundamental role in the early stages of skeletal development, specif ically those involved in the formation of prechondrogenic condensation s and their subsequent differentiation into chondroblasts. Microsc. Re s. Tech. 43:137-155, 1998. (C) 1998 Wiley-Liss, Inc.