ATVB In Focus Developmental Biology in the Vasculature Series Editor: Mark Majesky, PhD Mechanisms of Vessel Branching Filopodia on Endothelial Tip Cells Lead the Way

Abstract—Filopodia, “the fingers that do the walking, ” have been identified on endothelial cells at the tip of sprouting vessels for half a century, but the key role of the tip cell in vessel branching has been recognized only in the past few years. A model is emerging, whereby tip cells lead the way in a branching vessel, stalk cells elongate the sprout, and a very recently discovered phalanx cell ensures quiescence and perfusion of the newly formed branch. Recent genetic studies have shed light on the molecular signature of these distinct endothelial phenotypes; this provides a novel conceptual framework of how vessel morphogenesis occurs. Here, we will discuss the molecular candidates that participate in the decision of endothelial cells to adapt these distinct fates and highlight the emerging insights on how these cells send out filopodia while navigating. (Arterioscler Thromb Vasc Biol. 2009;29:639-649.) Key Words: endothelial tip cells stalk cells phalanx cells filopodia sprouting angiogenesis Much has been learned about the importance of angio-genesis in health and disease, but our understanding of how vessels branch remains incomplete. An exciting break-through in the field has been the recognition that several types of specialized endothelial cells (ECs), each with distinct cellular fate specifications, are required to build a functional branch.1 The first and, to a certain extent, the most undertak