Notch signaling in vascular development.
Notch signaling is an extremely conserved and widely used mechanism regulating cell fate in metazoans. Interaction of Notch receptors (Notch) with their ligands (Delta-like or Jagged) leads to cleavage of the Notch intracellular domain (NICD) that migrates into the nucleus. In the nucleus, NICD associates with a transcription factor, RBP-Jk. The NICD-RBP-Jk complex, in turn, upregulates expression of primary target genes of Notch signaling, such as hairy and enhancer of split (HES) and HES-related repressor protein (HERP) transcriptional repressors. Recent evidence has demonstrated that the Notch pathway is involved in multiple aspects of vascular development, including proliferation, migration, smooth muscle differentiation, angiogenic processes, and arterial-venous differentiation. In this brief review, we focus on ligands, receptors, and target genes of Notch signaling in the vascular system and discuss (1) tissue distribution; (2) gain- and loss-of-function studies; and (3) the role of Notch components in human diseases involving the vascular system.
Iso
Tatsuya
T
Second Department of Internal Medicine, Gunma University School of Medicine, Gunma 371-8511, Japan.
Hamamori
Yasuo
Y
Kedes
Larry
L
D016738:Alagille Syndrome / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins; D002319:Cardiovascular System / Q000196:embryology* / Q000254:growth & development; D002352:Carrier Proteins / Q000502:physiology; D015161:Dementia, Multi-Infarct / Q000235:genetics; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D046911:Macromolecular Substances; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051881:Receptor, Notch1; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000502:physiology*; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D014714:Vertebrates / Q000196:embryology / Q000235:genetics
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C490504:JAG2 protein, human; C000606274:Jag1 protein, mouse; C490503:Jag2 protein, mouse; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D046911:Macromolecular Substances; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C106075:NOTCH4 protein, human; C497762:Notch1 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; C073572:Notch4 protein, mouse