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

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 Writ signaling negatively regulated first heart field speck fication. We inactivated the obligate canonical Writ effector beta-catenin using a beta-catenin conditional null allele and the Mef2c AHF cre driver that directs cre activity specifically in SHF. We also expressed a stabilized form of beta-catenin to model continuous Writ signaling in SHF. Our data indicate that Writ signaling acts in a positive fashion to promote right ventricular and interventricular myocardial expansion. Cyclin D2 and Tgf beta 2 expression was drastically reduced in beta-catenin loss-of-function mutants, indicating that Writ signaling is required for patterning and expansion of SHF derivatives. Our findings reveal that Writ signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium.