Positive and negative feedback mechanisms controlling tip/stalk cell identity during sprouting angiogenesis

Vascular endothelial growth factor-A (VEGF-A/VEGF) interaction with VEGF receptor 2 (VEGFR2) is key for sprouting angiogenesis in health and disease. VEGF/VEGFR2 signaling promotes endothelial proliferation and migration, as well as the hierarchical organization into leader (tip) and follower (stalk) cells via a dynamic interplay with Notch. Recent studies reveal novel molecular mechanisms to fine-tune VEGF/Notch signaling and tip/stalk cell function during sprouting angiogenesis.