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Once it is initiated by environmental growth factor signals, the sprouting process is spearheaded by leading endothelial tip cells (Gerhardt et al., 2003)(Figure 1). Stimulated by vascular endothelial growth factor-A (VEGF-A), these cells produce long, dynamic filopodia studded with the tyrosine kinase receptor VEGFR2/KDR/Flk-1 and other receptors, whicthey use to probe the environment for directional cues. The endothelial cells that follow the tip cells, termed stalk cells,produce fewer filopodia and instead proliferate when stimulated with VEGF-A (Gerhardt et al., 2003). They also form the vascular lumen and they establish adherens and tight junctions tomaintain the integrity of the new sprout and to establish luminal/abluminal polarity, which, in turn, leads to basal lamina deposition and mural cell recruitment/attachment. Endothelial tip and stalk cells also differ in their gene expression profile; tip cells express Pdgfb, Dll4, Unc5b, Kdr, and Flt4more strongly than stalk cells |
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