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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Retinoid-Induced Limb Malformations

Author(s): Grace S. Lee, Devendra M. Kochhar and Michael D. Collins

Volume 10, Issue 22, 2004

Page: [2657 - 2699] Pages: 43

DOI: 10.2174/1381612043383728

Price: $65


The developing limb has been studied extensively and is a useful model to study morphogenesis. During embryogenesis, limb formation is initiated as a budding off from the embryonic lateral body wall. Limb pattern is specified by a series of epithelial-mesenchymal interactions, directing proximodistal, dorsoventral and anteroposterior axes. Vitamin A metabolites, especially retinoic acid, are known to play an important role in limb development, and the effects of retinoic acid may be mediated through the retinoid receptor signaling pathways. Accumulated evidence has shown that inadequate levels (excess or deficiency) of retinoic acid cause a wide range of limb malformations. Some species have the capacity to regenerate amputated limbs, and retinoids certainly affect this process, but there is debate regarding the extent that regeneration recapitulates development. In this review, phenotypic features, pathogenesis and the molecular basis of retinoid-induced limb malformations are discussed with a description of normal limb development and endogenous retinoid pathways.

Keywords: retinoid, retinoic acid, limb development, limb defects, congenital malformations

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