TY - JOUR
T1 - Retinoid X receptor-selective ligands produce malformations in Xenopus embryos
AU - Minucci, Saverio
AU - Saint-Jeannet, Jean Pierre
AU - Toyama, Reiko
AU - Scita, Giorgio
AU - Deluca, Luigi M.
AU - Taira, Masanori
AU - Levin, Arthur A.
AU - Ozato, Keiko
AU - Dawid, Igor B.
PY - 1996/3/5
Y1 - 1996/3/5
N2 - 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.
AB - 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.
KW - retinoic acid receptor
KW - retinoids
KW - Xenopus laevis
KW - zebrafish
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UR - http://www.scopus.com/inward/citedby.url?scp=0030010302&partnerID=8YFLogxK
U2 - 10.1073/pnas.93.5.1803
DO - 10.1073/pnas.93.5.1803
M3 - Article
C2 - 8700839
AN - SCOPUS:0030010302
VL - 93
SP - 1803
EP - 1807
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5
ER -