TARGETED NULL-MUTATION IN THE VASCULAR ENDOTHELIAL-CADHERIN GENE IMPAIRS THE ORGANIZATION OF VASCULAR-LIKE STRUCTURES IN EMBRYOID BODIES

Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed i n endothelial cells and is strictly located at cell-to-cell junctions. As the other members of the cadherin family, VE-cadherin is able to m ediate a homotypic type of cellular interaction in a Ca2+-dependent ma nner. 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 vasc ular structures, we generated VE-cadherin negative mouse embryonic ste m cells (VE-cadherin(-/-) ES cells) by gene targeting and examined the consequences on vascular development of ES-derived embryoid bodies (E Bs), In contrast to wild-type EBs, we observed that endothelial cells remained dispersed and failed to organize a vessel-like pattern in VE- cadherin(-/-) ES-derived EBs, However, dispersed VE-cadherin(-/-) ES-d erived endothelial cells expressed a large range of other endothelial markers, Moreover, the targeted null-mutation in the VE-cadherin locus did not interfere with the hematopoietic differentiation potential of ES cells, These irt vitro experiments are consistent with a pivotal r ole of VE-cadherin in vascular structure assembly.