Myocardial β-Catenin-BMP2 signaling promotes mesenchymal cell proliferation during endocardial cushion formation

Yidong Wang, Pengfei Lu, Bingruo Wu, Dario F. Riascos-Bernal, Nicholas E.S. Sibinga, Tomas Valenta, Konrad Basler, Bin Zhou

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Abnormal endocardial cushion formation is a major cause of congenital heart valve disease, which is a common birth defect with significant morbidity and mortality. Although β-catenin and BMP2 are two well-known regulators of endocardial cushion formation, their interaction in this process is largely unknown. Here, we report that deletion of β-catenin in myocardium results in formation of hypoplastic endocardial cushions accompanying a decrease of mesenchymal cell proliferation. Loss of β-catenin reduced Bmp2 expression in myocardium and SMAD signaling in cushion mesenchyme. Exogenous BMP2 recombinant proteins fully rescued the proliferation defect of mesenchymal cells in cultured heart explants from myocardial β-catenin knockout embryos. Using a canonical WNT signaling reporter mouse line, we showed that cushion myocardium exhibited high WNT/β-catenin activities during endocardial cushion growth. Selective disruption of the signaling function of β-catenin resulted in a cushion growth defect similar to that caused by the complete loss of β-catenin. Together, these observations demonstrate that myocardial β-catenin signaling function promotes mesenchymal cell proliferation and endocardial cushion expansion through inducing BMP signaling.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume123
DOIs
StatePublished - Oct 2018

Keywords

  • BMP
  • Congenital heart valve disease
  • Endocardial cushion formation
  • β-Catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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