Endothelial cells divide unequally to sprout fairly

Collective cell migration requires groups of cells to establish a hierarchy of cellular identities that coordinates their movement. During new blood vessel branching by angiogenesis, this takes the form of a single endothelial “tip cell” that leads nascent vessels and is followed by endothelial “stalk cells”. Tip cells are highly motile and navigate sprouting vessels by sensing chemotactic stimuli such as vascular endothelial growth factor (VEGF). In contrast, stalk cells are less motile and form the trunk of developing vessels. As new vessels grow, migrating endothelial cells must also proliferate which presents tip cells with a problem, as each daughter cell must acquire a different migratory profile dependent on their resultant position. The more distal daughter takes on tip cell identity, while the more proximal daughter becomes the trailing stalk cell. Rapid re-establishment of this leader-follower hierarchy is critical to ensuring collective cell migration is not disrupted during proliferative growth, but how this occurs is unclear.