Biomechanical gradients and early vasculogenic patterns

Vasculogenesis occurs within constantly expanding tissues. Explanted mouse allantoic endothelial cells (ECs) assemble a vascular network, de novo, when placed in culture. The allantoic network is situated on the upper surface of a mesothelium that expands ten‐fold during the process. Similarly, quail embryos manifest vast tissue expansion during vasculogenesis. Computational time‐lapse imaging allows quantification of primordial EC motility, as well as the motion of surrounding tissue. Allantoic ECs at the base of multicellular sprouts normally move distally “over” existing sprout cells to form new tip‐cells; and loss of VE‐Cadherin activity prevents this motile behavior. Other time‐lapse data suggest that EC sprouts respond to mechanical gradients and favor locomotion along rigid biological structures — such as cords of cells or bundles of ECM. We propose a mechanically‐based morphogenetic field in which primordial ECs initially extend sprouts using integrin‐ECM adhesions. Once formed, however, movement of “new” sprout tip cells is mediated by VE‐cadherin based motility. Certain sprout “base” cells appear to be mechanically stimulated to become motile and move distally to replace existing tip cells — so that advancing vascular sprouts can “keep‐up” with the expanding tissues. Thus, endogenous biomechanical tissue gradients partially govern assembly of vascular networks in warm‐blooded animals.