'In vivo' analysis of junctional dynamics underlying angiogenic cell behaviors

The blood circulatory system delivers nutrients and oxygen to tissues and organs. Moreover, the circulatory system retains high plasticity throughout an organism’s life, which is important for physiological processes, such as wound healing, but also during pathological processes, such as tumor growth. Blood vessels can sprout from existing ones, a process called angiogenesis, to create a more branched network that reaches avascular and the most distal parts of an animal body. The morphogenetic processes that underlie angiogenesis can be studied at cellular resolution in the zebrafish embryo. Moreover, the fast development of the embryo allows to follow these processes in real-time. In the trunk, where metameric vessels sprout from the dorsal aorta, cells migrate collectively in a hierarchy defined by a leading endothelial cell at the tip of the sprout and several following cells, called stalk cells. Once the tip cells reach the level of the dorsal neural tube, they extend laterally and initiate the anastomosis process with tip cells from the neighboring segments. Eventually, cells rearrange and form a patent lumen, which allows blood circulation. Angiogenic sprout outgrowth and anastomosis involve complex cell behaviors and cell-cell interactions, which need to be precisely orchestrated. The molecular mechanisms underlying these cellular activities are not known. However, proteins that mediate endothelial specific cell adhesion are good candidates to promote concerted cell behaviors. The goal of my thesis was (i) to characterize the cell shape changes that occur during angiogenic sprouting, (ii) to analyze the function of VE-cadherin in this process and (iii) to analyze the role of VE-cadherin and Esama, as candidate proteins, in the initiation of endothelial cell-cell interaction at the onset of vascular anastomosis. I found that two major cell behaviors contribute to angiogenic sprouting. While cell migration is predominantly used by the tip cell, elongation of the stalk is mainly achieved by extensive stalk ...