Regulation and regulatory role of the retinoids.
Retinoids regulate differentiation and cellular growth, exerting their physiological action by interacting with two families of nuclear receptors, the retinoic acid receptors (RARs), and the retinoid X receptors (RXRs), which regulate gene expression by forming transcriptionally active heterodimeric RAR/RXR or homodimeric RXR/RXR complexes on DNA. Although RAR/RXR heterodimers form preferentially in vitro and in vivo, it does not exclude the possibility that RXR/RXR homodimers may regulate a distinct signaling pathway. Synthetic retinoids that selectively activate or antagonize retinoic acid receptor isoforms promises to be useful tools for the elucidation of specific retinoid response pathways. Considerable progress has been made in understanding the molecular basis underlying limb bud formation, particularly the manner in which retinoic acid interacts with other signaling molecules to determine pattern formation. The phenotypic abnormalities observed in compound null mutants of retinoid receptors, recapitulating those described in the vitamin A deficiency syndrome, confirm the crucial function of endogenous retinoids in fetal development. However, the absence of phenotypic abnormalities in null mutants of individual RAR isoforms raises the possibility of functional redundancy among RAR subtypes and at the same time challenging the concept that the diverse effects of retinoids are related to the multiplicity of fnctionally distinct receptors.