title: Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors.
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, beta-catenin, is unknown. Using tissue-specific in vivo genetic manipulation, we found that beta-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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease and Department of Pediatrics, University of California, 1650 Owens Street, San Francisco, CA 94158, USA.
authors.forename: Chulan
authors.initials: C
authors.lastname: Kwon
authors.forename: Joshua
authors.initials: J
authors.lastname: Arnold
authors.forename: Edward C
authors.initials: EC
authors.lastname: Hsiao
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Conklin
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004627:Embryonic Induction; D008648:Mesoderm; D051379:Mice; D008815:Mice, Inbred Strains; D039902:Multipotent Stem Cells / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins