β-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis

Recent studies have demonstrated that the LIM homeodomain transcription factor Islet1 (IsI1) marks pluripotent cardiovascular progenitor cells and is required for proliferation, survival, and migration of recently defined second heart field progenitors. Factors that are upstream of IsI1 in cardiovascular progenitors have not yet been defined. Here we demonstrate that beta-catenin is required for IsI1 expression in cardiac progenitors, directly regulating the IsI1 promoter. Ablation of beta-catenin in IsI1-expressing progenitors disrupts multiple aspects of cardiogenesis, resulting in embryonic lethality at E13. beta-Catenin is also required upstream of a number of genes required for pharyngeal arch, outflow tract, and/or atrial septal morphogenesis, including Tbx2, Tbx3, Wnt11, Shh, and Pitx2. Our findings demonstrate that beta-catenin signaling regulates proliferation and survival of cardiac progenitors.