Transforming growth factor β2 is negatively regulated by endogenous retinoic acid during early heart morphogenesis

Satish K. Ghatpande, Hui Ren Zhou, Inese Cakstina, Christopher Carlson, Elizabeth A. Rondini, Mahmoud Romeih, Maija H. Zile

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Vitamin A-deficient (VAD) quail embryos lack the vitamin A-active form, retinoic acid (RA) and are characterized by a phenotype that includes a grossly abnormal cardiovascular system that can be rescued by RA. Here we report that the transforming growth factor, TGFβ2 is involved in RA-regulated cardiovascular development. In VAD embryos TGFβ2 mRNA and protein expression are greatly elevated. The expression of TGFβ receptor II is also elevated in VAD embryos but is normalized by treatment with TGFβ2-specific antisense oligonucleotides (AS). Administration of this AS or an antibody specific for TGFβ2 to VAD embryos normalizes posterior heart development and vascularization, while the administration of exogenous active TGFβ2 protein to normal quail embryos mimics the excessive TGFβ2 status of VAD embryos and induces VAD cardiovascular phenotype. In VAD embryos pSmad2/3 and pErk1 are not activated, while pErk2 and pcRaf are elevated and pSmad1/5/8 is diminished. We conclude that in the early avian embryo TGFβ2 has a major role in the retinoic acid-regulated posterior heart morphogenesis for which it does not use Smad2/3 pathways, but may use other signaling pathways. Importantly, we conclude that retinoic acid is a critical negative physiological regulator of the magnitude of TGFβ2 signals during vertebrate heart formation.

Original languageEnglish
Pages (from-to)433-455
Number of pages23
JournalDevelopment Growth and Differentiation
Issue number5
Publication statusPublished - Jun 2010
Externally publishedYes


  • Cardiovascular morphogenesis
  • Quail embryo
  • Transforming growth factor β2
  • Vitamin A

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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