Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors

Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Writ pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Writ ligands are thought to negatively regulate cardiorryogenesis 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 Writ 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 Writ signaling promotes the expansion of cardiac progenitors and differentiation of cardiornyocytes.