Multicellular sprouting during vasculogenesis.

Living organisms, from bacteria to vertebrates, are well known to generate sophisticated multicellular patterns. Numerous recent interdisciplinary studies have focused on the formation and regulation of these structures. Advances in automatized microscopy allow the time-resolved tracking of embryonic development at cellular resolution over an extended area covering most of the embryo. The resulting images yield simultaneous information on the motion of multiple tissue components-both cells and extracellular matrix (ECM) fibers. Recent studies on ECM displacements in bird embryos resulted in a method to distinguish tissue deformation and cell-autonomous motion. Patterning of the primary vascular plexus results from a collective action of primordial endothelial cells. The emerging "polygonal" vascular structure is shown to be formed by cell-cell and cell-ECM interactions: adhesion and protrusive activity (sprouting). Utilizing avb3 integrins, multicellular sprouts invade rapidly into avascular areas. Sprout elongation, in turn, depends on a continuous supply of endothelial cells. Endothelial cells migrate along the sprout, towards its tip, in a vascular endothelial (VE) cadherin-dependent process. The observed abundance of multicellular sprout formation in various in vitro and in vivo systems can be explained by a general mechanism based on preferential attraction to elongated structures. Our interacting particle model exhibits robust sprouting dynamics and results in patterns with morphometry similar to native primordial vascular plexuses--without ancillary assumptions involving chemotaxis or mechanochemical signaling.