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

Abstract

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.

Keywords: Adherens Junctions; Cadherins; Cardiac progenitors; Embryonic Stem Cells; FLK1; ISL1; MEF2C; N-CADHERIN; VE-CADHERIN.