Canonical Wnt signaling functions in second heart field to promote right ventricular growth

Di Ai, Xueyao Fu, Jun Wang, Mei Fang Lu, Li Chen, Antonio Baldini, William H. Klein, James F. Martin

Research output: Contribution to journalArticlepeer-review

Abstract

The second heart field (SHF), progenitor cells that are initially sequestered outside the heart, migrates into the heart and gives rise to endocardium, myocardium, and smooth muscle. Because of its distinct developmental history, the SHF is likely subjected to different signals from that of the first heart field. Previous experiments revealed that canonical Wnt signaling negatively regulated first heart field specification. We inactivated the obligate canonical Wnt effector β-catenin using a β-catenin conditional null allele and the Mef2c AHF cre driver that directs cre activity specifically in SHF. We also expressed a stabilized form of β-catenin to model continuous Wnt signaling in SHF. Our data indicate that Wnt signaling acts in a positive fashion to promote right ventricular and interventricular myocardial expansion. Cyclin D2 and Tgfβ2 expression was drastically reduced in β-catenin loss-of-function mutants, indicating that Wnt signaling is required for patterning and expansion of SHF derivatives. Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium.

Original languageEnglish
Pages (from-to)9319-9324
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number22
DOIs
Publication statusPublished - May 29 2007

Keywords

  • Cardiac progenitor
  • Conditional genetics
  • Development
  • Mouse

ASJC Scopus subject areas

  • Genetics
  • General

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