VE-CADHERIN is expressed transiently in early ISL1(+) cardiovascular progenitor cells and facilitates cardiac differentiation

Adherens junctions (AJs) provide adhesive properties through cadherins and associated cytoplasmic catenins and participate in morphogenetic processes. We examined AJs formed between ISL1(+) cardiovascular progenitor cells during differentiation of embryonic stem cells (ESCs) in vitro and in mouse embryogenesis in vivo. We found that, in addition to N-CADHERIN, a percentage of ISL1(+) cells transiently formed vascular endothelial (VE)-CADHERIN-mediated AJs during in vitro differentiation on days 4 and 5, and the same pattern was observed in vivo. Fluorescence-activated cell sorting (FACS) analysis extended morphological data showing that VE-CADHERIN(+)/ISL1(+) cells constitute a significant percentage of cardiac progenitors on days 4 and 5. The VE-CADHERIN(+)/ISL1(+) cell population represented one-third of the emerging FLK1(+)/PDGFRa(+) cardiac progenitor cells (CPCs) for a restricted time window (days 4–6). Ablation of VE-CADHERIN during ESC differentiation results in severe inhibition of cardiac differentiation. Disruption of all classic cadherins in the VE-CADHERIN(+) population via a cadherin dominant-negative mutant’s expression resulted in a dramatic decrease in the ISL1(+) population and inhibition of cardiac differentiation.