title: Retinoid X receptor-selective ligands produce malformations in Xenopus embryos.
abstract: Retinoids exert pleiotropic effects on the development of vertebrates through the action of retinoic acid receptors (RAR) and retinoid X receptors (RXR). We have investigated the effect of synthetic retinoids selective for RXR and RAR on the development of Xenopus and zebrafish embryos. In Xenopus, both ligands selective for RAR and RXR caused striking malformations along the anterior-posterior axis, whereas in zebrafish only ligands specific for RAR caused embryonic malformations. In Xenopus, RAR- and RXR-selective ligands regulated the expression of the Xlim-1, gsc, and HoxA1 genes similarly as all-trans-retinoic acid. Nevertheless, RXR-selective ligands activated only an RXR responsive reporter but not an RAR responsive reporter introduced by microinjection into the Xenopus embryo, consistent with our failure to detect conversion of an RXR-selective ligand to different derivatives in the embryo. These results suggest that Xenopus embryos possess a unique response pathway in which liganded RXR can control gene expression. Our observations further illustrate the divergence in retinoid responsiveness between different vertebrate species.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Minucci
authors.forename: J P
authors.initials: JP
authors.lastname: Saint-Jeannet
authors.forename: R
authors.initials: R
authors.lastname: Toyama
authors.forename: G
authors.initials: G
authors.lastname: Scita
authors.forename: L M
authors.initials: LM
authors.lastname: DeLuca
authors.forename: M
authors.initials: M
authors.lastname: Tiara
authors.forename: A A
authors.initials: AA
authors.lastname: Levin
authors.forename: K
authors.initials: K
authors.lastname: Ozato
authors.forename: I B
authors.initials: IB
authors.lastname: Dawid
mesh_terms: D000818:Animals; D000013:Congenital Abnormalities / Q000196:embryology; D015870:Gene Expression / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D008024:Ligands; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors