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

Angiogenesis. 2020 May;23(2):75-77. doi: 10.1007/s10456-020-09706-0.

Abstract

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.

Keywords: Dll4; ERK; Notch; Sprouting angiogenesis; Tip cells; VEGF signaling.

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Cell Lineage / genetics
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / growth & development
  • Endothelium, Vascular / metabolism
  • Feedback, Physiological / physiology*
  • Humans
  • MAP Kinase Signaling System / physiology
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Morphogenesis / genetics
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / therapy
  • Neovascularization, Physiologic / physiology*
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Receptors, Notch
  • Vascular Endothelial Growth Factor A