Regulation of vascular morphogenesis by Notch signaling.
The Notch pathway is a versatile regulator of cell fate specification, growth, differentiation, and patterning processes in metazoan organisms. In the vertebrate cardiovascular system, multiple Notch family receptors and several of their Jagged and Delta-like ligands are expressed during critical stages of embryonic and postnatal development. Functional studies in mice, fish, tumor models, and cell culture systems have shown that the angiogenic growth of the blood vessel network, the proliferation of endothelial cells, and the differentiation of arteries and veins are controlled by Notch signaling. Moreover, Notch pathway components play important roles in human pathological conditions involving the vasculature, namely CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and Alagille syndrome. Recent findings highlight the Notch ligand Delta-like 4 as a key regulator of tumor angiogenesis and suggest that this protein might be a promising target for cancer therapy.
Roca
Cristina
C
Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom.
Adams
Ralf H
RH
D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008955:Models, Cardiovascular; D009024:Morphogenesis / Q000235:genetics; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D020239:Receptor Cross-Talk; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D014652:Vascular Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A