Targeted null-mutation in the <i>vascular endothelial–cadherin</i> gene impairs the organization of vascular-like structures in embryoid bodies

<jats:p> Vascular endothelial–cadherin (VE–cadherin) is exclusively expressed in endothelial cells and is strictly located at cell-to-cell junctions. As the other members of the cadherin family, VE–cadherin is able to mediate a homotypic type of cellular interaction in a Ca <jats:sup>2+</jats:sup> -dependent manner. In the mouse embryo, VE–cadherin transcripts are detected at the earliest stages of vascular development. To ascertain if VE–cadherin expression is required for the assembly of endothelial cells into vascular structures, we generated <jats:italic>VE–cadherin</jats:italic> -negative mouse embryonic stem cells ( <jats:italic>VE–cadherin</jats:italic> <jats:sup>−/−</jats:sup> ES cells) by gene targeting and examined the consequences on vascular development of ES-derived embryoid bodies (EBs). In contrast to wild-type EBs, we observed that endothelial cells remained dispersed and failed to organize a vessel-like pattern in <jats:italic>VE–cadherin</jats:italic> <jats:sup>−/−</jats:sup> ES-derived EBs. However, dispersed <jats:italic>VE–cadherin</jats:italic> <jats:sup>−/−</jats:sup> ES-derived endothelial cells expressed a large range of other endothelial markers. Moreover, the targeted null-mutation in the <jats:italic>VE–cadherin</jats:italic> locus did not interfere with the hematopoietic differentiation potential of ES cells. These <jats:italic>in vitro</jats:italic> experiments are consistent with a pivotal role of VE–cadherin in vascular structure assembly. </jats:p>