DIFFERENTIAL EXPRESSION OF RETINOIC ACID RECEPTOR-BETA ISOFORMS DURING CHICK LIMB ONTOGENY

Retinoids influence both morphogenetic events and differentiation duri ng development of the vertebrate limb. These effects are mediated thro ugh nuclear retinoid receptors, which modulate target gene expression. We report here the cloning and characterization of three promoter- an d splicing-variants of the retinoic acid receptor-beta (RAR-beta) from chick. These receptor isoforms are independently expressed during lim b development. RAR beta 2 but not RAR beta 1 transcripts are enriched three-fold in the posterior limb bud, reflecting the increased RA conc entrations in this region. RAR beta 1 transcripts are initially presen t throughout the limb bud mesenchyme and ectoderm, then become restric ted within perichondrial regions and loose connective tissue of the li mb. RAR beta 1 expression closely overlaps that of NCAM (neural cell a dhesion molecule) and tenascin in non-neuronal tissues. RAR beta 2 tra nscripts are present within a subset of those limb tissues which expre ss RAR beta 1. In the early limb bud RAR beta 2 transcripts are detect ed in proximal limb mesenchyme and in the initial mesenchymal condensa te. In older limbs RAR beta 2 mRNAs are abundant in cells lateral to t he digit cartilage. Neither RAR beta 1 nor RAR beta 2 transcripts are associated specifically with regions of limb cell death. The different ial expression and regulation of RAR beta isoforms suggests these vari ants may have different roles in limb development. (C) 1995 Wiley-Liss , Inc.