Frzb modulates Wnt-9a-mediated β-catenin signaling during avian atrioventricular cardiac cushion development

Anthony D. Person, Robert J. Garriock, Paul A. Krieg, Raymond B. Runyan, Scott E. Klewer

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Normal development of the cardiac atrioventricular (AV) endocardial cushions is essential for proper ventricular septation and morphogenesis of the mature mitral and tricuspid valves. In this study, we demonstrate spatially restricted expression of both Wnt-9a (formerly Wnt-14) and the secreted Wnt antagonist Frzb in AV endocardial cushions of the developing chicken heart. Wnt-9a expression is detected only in AV canal endocardial cells, while Frzb expression is detected in both endocardial and transformed mesenchymal cells of the developing AV cardiac cushions. We present evidence that Wnt-9a promotes cell proliferation in the AV canal and overexpression of Wnt-9a in ovo results in enlarged endocardial cushions and AV inlet obstruction. Wnt-9a stimulates β-catenin-responsive transcription in AV canal cells, duplicates the embryonic axis upon ventral injections in Xenopus embryos and appears to regulate cell proliferation by activating a Wnt/β-catenin signaling pathway. Additional functional studies reveal that Frzb inhibits Wnt-9a-mediated cell proliferation in cardiac cushions. Together, these data argue that Wnt-9a and Frzb regulate mesenchymal cell proliferation leading to proper AV canal cushion outgrowth and remodeling in the developing avian heart.

Original languageEnglish (US)
Pages (from-to)35-48
Number of pages14
JournalDevelopmental biology
Volume278
Issue number1
DOIs
StatePublished - Feb 1 2005

Keywords

  • Apoptosis
  • Cardiac
  • Cell proliferation
  • Endocardial cushions
  • Epithelial-mesenchymal transition (EMT)
  • Frzb
  • Heart
  • Wnt-14
  • Wnt-9a
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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