Collections > Electronic Theses and Dissertations > Multiple endothelial cells constitute the tip of developing blood vessels and polarize to promote lumen formation.

Blood vessel polarization in the apical-basal axis is important for directed secretion of proteins and lumen formation, yet when and how polarization occurs in the context of angiogenic sprouting is not well understood. The canonical model of angiogenic sprouts is a single cell, the tip cell, at the front of the sprout. I describe a novel topology for endothelial cells at the front of angiogenic sprouts in several mammalian vascular beds that disputes the classic tip cell model, and by using confocal and live imaging of mosaically-labeled endothelial cells I show that two cells significant overlap in space and time at the front of vessels, both in vitro and in vivo. The overlap is more extensive than predicted for tip cell switching, and it sets up a longitudinal cell-cell border that is apical polarization and lumen formation, presumably via a cord hollowing mechanism. The extent of cell overlap at the tip is reduced in mice lacking aPKCζ, and this is accompanied by reduced distal extension of both the apical border and patent lumens. Thus at least two cells occupy the tip of angiogenic sprouts for long periods of time, and apical-basal polarization that is influenced by aPKCζ is close to the distal tips of blood vessel sprouts.