Endothelial tip cells in development and disease – EGC

Angiogenesis is a complex morphogenetic process that requires coordinated migration, proliferation and differentiation of endothelial cells. Numerous studies carried out during the past decade have established that developmental and pathological angiogenesis are driven by the vascular endothelial growth factor (VEGF) and its high-affinity tyrosine kinase receptors VEGFR1 and 2, which are expressed on the endothelial cell surface. VEGF regulates endothelial proliferation, survival and differentiation. Four types of endothelial cells can currently be distinguished by morphological characteristics and gene expression patterns. These include arterial, venous, and lymphatic endothelial cells as well as endothelial tip cells, which are specialized lumen-less endothelial cells localized at the tips of growing capillaries. Tip cells are morphologically distinguished from the subjacent endothelial stalk cells by their extension of numerous long slender filopodial protrusions. These cells integrate directional cues from their environment and so define the direction in which the new sprout grows. Tip cells also find and create connections with adjacent sprouts, and so generate functional vascular networks. - The objective of the current proposal is to identify the signaling mecanisms regulating tip cell behavior during vascular development and to determine their importance in vascular pathologies, including retinopathies and tumor angiogenesis. - ...