Blood vessels are essential conduits of nutrients and oxygen throughout the body. The formation of these vessels involves angiogenic sprouting, a complex process entailing highly integrated cell behaviors and signaling pathways. In this review, we discuss how endothelial cells initiate a vessel sprout through interactions with their environment and with one another, particularly through lateral inhibition. We review the composition of the local environment, which contains an initial set of guidance cues to facilitate the proper outward migration of the sprout as it emerges from a parent vessel. The long-range guidance and sprout stability cues provided by soluble molecules, extracellular matrix components, and interactions with other cell types are also discussed. We also examine emerging evidence for mechanisms that govern sprout fusion with its target and lumen formation.
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