The Tip Cell Concept Ten Years After : New Players Tune in for a Common Theme

Embryonic growth, organ formation and regeneration rely on properly patterned vascular networks. During these processes, tissue growth is accompanied by an expansion of the respective vascular beds by angiogenesis. Angiogenesis involves the sprouting of new vessels from pre-existing ones and the eventual fusion of these sprouts with other sprouts or blood vessels to form new vascular loops. Sprouting blood vessels are made up of different cell populations: leading tip cells, which guide the sprout, and following stalk cells, which make up the base of the sprout and maintain the connection to the parental vessel. The functional and molecular differences between tip and stalk cells and how such differences ensure proper angiogenesis has drawn great attention within the last decade. In this review, we present recent progress in our understanding of tip cell specification and function during sprouting angiogenesis and anastomosis. We furthermore discuss similarities and variations in tip cell biology in different vascular beds and how they might be important for the formation of structurally and functionally distinct vascular networks.