NOTCH maintains developmental cardiac gene network through WNT5A

Yidong Wang, Pengfei Lu, Bingruo Wu, Bernice E. Morrow, Bin Zhou

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

NOTCH and WNT signaling pathways play critical roles in cardiac chamber formation. Here we explored the potential interactions between the two pathways in this developmental process by using genetically modified mouse models and whole embryo culture systems. By deletion of Notch1 to inactivate NOTCH1 signaling in the endocardium in vivo and ex vivo rescue experiments, we showed that myocardial WNT5A mediated endocardial NOTCH1 signaling to maintain the gene regulatory network essential for cardiac chamber formation. Furthermore, genetic deletion of β-catenin in the myocardium and inhibition of the WNT/Ca 2+ signaling by FK506 resulted in a similar disruption of the gene regulatory network as inactivation of endocardial NOTCH1 signaling. Together, these findings identify WNT5A as a key myocardial factor that mediates the endocardial NOTCH signaling to maintain the gene regulatory network essential for cardiac chamber formation through WNT/β-catenin and WNT/Ca 2+ signaling pathways.

Original languageEnglish (US)
Pages (from-to)98-105
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume125
DOIs
StatePublished - Dec 2018

Keywords

  • Cardiac chamber formation
  • Cardiac gene network
  • NOTCH
  • WNT

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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