PMID: 9006080Jan 1, 1997Paper

Ligand-bound RXR can mediate retinoid signal transduction during embryogenesis

Development
H C LuC Thaller

Abstract

Retinoids regulate various aspects of vertebrate development through the action of two types of receptors, the retinoic acid receptors (RARs) and the retinoid-X-receptors (RXRs). Although RXRs bind 9-cis-retinoic acid (9cRA) with high affinity, in vitro experiments suggest that RXRs are for the most part not liganded, but serve as auxiliary factors forming heterodimers with liganded partner receptors such as RAR. Here we have used RXR- and RAR-specific ligands 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-napthyl)ethenyl]b enzoic acid (LG69) and (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-prope nyl]benzoic acid (TTNPB), and show that, in the context of an embryo, liganded RXR can mediate retinoid signal transduction. This conclusion emerges from examining the induction of several retinoid-responsive genes in the limb bud (Hoxb-6/-8, RARbeta) and in the developing central nervous system (Hoxb-1, otx-2). RARbeta and Hoxb-1 genes were most effectively activated by a combination of TTNPB and LG69, suggesting that the activation of these genes benefits from the presence of ligand-bound RAR and ligand-bound RXR. Hoxb-6/-8 genes were most efficiently induced by LG69, suggesting that liganded RXR can activate ...Continue Reading

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