Hemodynamic Control of Endothelial Cell Fates in Development

The vascular system initially forms as a random network of capillaries, which remodels under the influence of flow into efficient, hierarchical vasculature. Blood flow determines the final expression pattern of arteriovenous markers and guides the pruning of excess vasculature, including the restructuring of the six pairs of aortic arches. Changes in blood flow can overrule arterial, venous, and lymphatic fates, causing both morphological and genetic switching between identities. Flow patterns are essential for determining locations of sprouting, regression, fusion, and intussusception, as well as for guiding the formation of both vascular and cardiac valves. The force of blood flow is detected by various mechanosensors on the luminal cell surface, in cell–cell junctions, and in contact with the ECM. These mechanosensors activate multiple interacting signaling cascades which are understood to play important roles in vascular development and endothelial cell fate specification.