Retinoid signaling can repress blastula Wnt signaling and impair dorsal development in Xenopus embryo.
Vitamin A derivatives (retinoids) are actively involved during vertebrate embryogenesis. However, exogenous retinoids have also long been known as potent teratogens. The defects caused by retinoid treatment are complex. Here, we provided evidence that RAR-mediated retinoid signaling can repress Xenopus blastula Wnt signaling and impair dorsal development. Exogenous retinoic acid (RA) could antagonize the dorsalizing effects of lithium chloride-mediated Wnt activation in blastula embryos. The Wnt-responsive reporter gene transgenesis and luciferase assay showed that excess RA can repress the Wnt signaling in blastula embryos. In addition, the downstream target genes of the Wnt signaling that direct embryonic dorsal development, were also down-regulated in the RA-treated embryos. Mechanically, RA did not interfere with the stability of beta-catenin, but promoted its nuclear accumulation. The inverse agonist of retinoic acid receptors (RAR) rescued the Wnt signaling repression by RA and relieved the RA-induced nuclear accumulation of beta-catenin. Our results explain one of the reasons for the complicated teratogenic effects of retinoids and shed light on the endogenous way of interactions between two developmentally important signaling pathways.
Li
Shuangwei
S
Key Laboratory of Stem Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai.
Lou
Xin
X
Wang
Jinhu
J
Liu
Bin
B
Ma
Lanping
L
Su
Zhepeng
Z
Ding
Xiaoyan
X
D000818:Animals; D036703:Blastula / Q000196:embryology / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000502:physiology; D012176:Retinoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D014981:Xenopus / Q000196:embryology; D051176:beta Catenin / Q000502:physiology
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D051153:Wnt Proteins; D051176:beta Catenin