Retinoid signaling can repress blastula Wnt signaling and impair dorsal development in Xenopus embryo.

Published

Journal Article

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.

Full Text

Cited Authors

  • Li, S; Lou, X; Wang, J; Liu, B; Ma, L; Su, Z; Ding, X

Published Date

  • October 2008

Published In

Volume / Issue

  • 76 / 8

Start / End Page

  • 897 - 907

PubMed ID

  • 18452549

Pubmed Central ID

  • 18452549

Electronic International Standard Serial Number (EISSN)

  • 1432-0436

International Standard Serial Number (ISSN)

  • 0301-4681

Digital Object Identifier (DOI)

  • 10.1111/j.1432-0436.2008.00269.x

Language

  • eng