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Retinoic acid receptors in normal growth and development.

Retinoic acid receptors are ligand activated transcription factors that have a variety of important roles in normal development, through regulating the transcription of other developmental control genes. The great diversity of RA mediated developmental events is made possible through the existence of three receptor subtypes, each of which has a number of isoforms. The mechanism of gene regulation is thought to involve binding to an RA response element on the target gene, although in practice, few genes known to be activated by RA have so far been demonstrated to include such an element in the promoter region. Differential spatiotemporal expression patterns of the various subtypes have been described in mouse embryos, including very fine differences within different subpopulations of cells of the same tissue. In addition to qualitative differences in the gene activation responses to RA through spatiotemporal differences in RAR expression patterns, local differences in RAR activation may be modulated by cytoplasmic binding proteins for retinol and RA, through quantitative control of ligand availability. The developmental control genes known to be activated by RA include the 3' members of each of the homoeogene clusters, and it is likely that others will be identified in the near future.