( cardiac development | embryonic stem cells |
-catenin | second heart field )
Chulan Kwon *
, Joshua Arnold *
, Edward C. Hsiao *
, Makoto M. Taketo
, Bruce R. Conklin *
¶, and Deepak Srivastava *
*Gladstone Institute of Cardiovascular Disease and Departments of Pediatrics, Medicine, ¶Cellular and Molecular Pharmacology, and ||Biochemistry and Biophysics, University of California, 1650 Owens Street, San Francisco, CA 94158; and Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo Kyoto 606-8501, Japan
Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved May 21, 2007 (received for review May 1, 2007)
Guiding multipotent cells into distinctblineages and controlling their expansion remain fundamentalbchallenges in developmental and stem cell biology. Members ofbthe Wnt pathway control many pivotal embryonic events, oftenbpromoting self-renewal or expansion of progenitor cells. Inbcontrast, canonical Wnt ligands are thought to negatively regulatebcardiomyogenesis in several species. However, the cell-autonomousbrole of canonical Wnt signaling within precardiac mesoderm,bthrough its obligatory transcriptional mediator, -catenin, isbunknown. Using tissue-specific in vivo genetic manipulation,bwe found that -catenin is required for development of cardiacbprogenitors and is a positive regulator of proliferative expansionbof such progenitor cells. At discrete windows of developmentbin embryonic stem cells, activation of canonical Wnt signalingbpromoted expansion of cardiac progenitors after initial commitmentband was required for cardiac differentiation. Together, thesebdata provide in vivo and in vitro evidence that canonical Wntbsignaling promotes the expansion of cardiac progenitors andbdifferentiation of cardiomyocytes.
Author contributions: C.K. and D.S. designed research; C.K. and J.A. performed research; E.C.H., M.M.T., and B.R.C. contributed new reagents/analytic tools; C.K. and D.S. analyzed data; and C.K. and D.S. wrote the paper.
The authors declare no conflict of interest.
**To whom correspondence should be addressed.