Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors

Chulan Kwon, Joshua Arnold, Edward C. Hsiao, Makoto M. Taketo, Bruce R. Conklin, Deepak Srivastava

Research output: Contribution to journalArticlepeer-review

Abstract

Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Wnt pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Wnt ligands are thought to negatively regulate cardiomyogenesis in several species. However, the cell-autonomous role of canonical Wnt signaling within precardiac mesoderm, through its obligatory transcriptional mediator, β-catenin, is unknown. Using tissue-specific in vivo genetic manipulation, we found that β-catenin is required for development of cardiac progenitors and is a positive regulator of proliferative expansion of such progenitor cells. At discrete windows of development in embryonic stem cells, activation of canonical Wnt signaling promoted expansion of cardiac progenitors after initial commitment and was required for cardiac differentiation. Together, these data provide in vivo and in vitro evidence that canonical Wnt signaling promotes the expansion of cardiac progenitors and differentiation of cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)10894-10899
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number26
DOIs
StatePublished - Jun 26 2007

Keywords

  • Cardiac development
  • Embryonic stem cells
  • Second heart field
  • β-catenin

ASJC Scopus subject areas

  • General

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