Differential expression of retinoic acid receptor‐β isoforms during chick limb ontogeny

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Abstract
Retinoids influence both morphogenetic events and differentiation during development of the vertebrate limb. These effects are mediated through nuclear retinoid receptors, which modulate target gene expression. We report here the cloning and characterization of three promoter‐ and splicing‐variants of the retinoic acid receptor‐β (RAR‐β) from chick. These receptor isoforms are independently expressed during limb development. RARβ2 but not RARβ1 transcripts are enriched three‐fold in the posterior limb bud, reflecting the increased RA concentrations in this region. RARβ1 transcripts are initially present throughout the limb bud mesenchyme and ectoderm, then become restricted within perichondrial regions and loose connective tissue of the limb. RARβ1 expression closely overlaps that of NCAM (neural cell adhesion molecule) and tenascin in non‐neuronal tissues. RARβ2 transcripts are present within a subset of those limb tissues which express RARβ1. In the early limb bud RARβ2 transcripts are detected in proximal limb mesenchyme and in the initial mesenchymal condensate. In older limbs RARβ2 mRNAs are abundant in cells lateral to the digit cartilage. Neither RARβ1 nor RARβ2 transcripts are associated specifically with regions of limb cell death. The differential expression and regulation of RARβ isoforms suggests these variants may have different roles in limb development.