Minucci S, Saint-Jeannet J P, Toyama R, Scita G, DeLuca L M, Tiara M, Levin A A, Ozato K, Dawid I B
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1803-7. doi: 10.1073/pnas.93.5.1803.
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.
维甲酸通过维甲酸受体（RAR）和类视黄醇X受体（RXR）的作用，对脊椎动物的发育产生多效性影响。我们研究了对RXR和RAR具有选择性的合成维甲酸对非洲爪蟾和斑马鱼胚胎发育的影响。在非洲爪蟾中，对RAR和RXR具有选择性的两种配体均导致沿前后轴出现明显的畸形，而在斑马鱼中，只有对RAR具有特异性的配体导致胚胎畸形。在非洲爪蟾中，对RAR和RXR具有选择性的配体对Xlim-1、gsc和HoxA1基因表达的调控与全反式维甲酸相似。然而，对RXR具有选择性的配体仅激活了一个RXR反应性报告基因，而没有激活通过显微注射导入非洲爪蟾胚胎的RAR反应性报告基因，这与我们未能在胚胎中检测到RXR选择性配体向不同衍生物的转化一致。这些结果表明，非洲爪蟾胚胎具有一种独特的反应途径，其中结合配体的RXR可以控制基因表达。我们的观察结果进一步说明了不同脊椎动物物种之间维甲酸反应性的差异。
