Notch signaling in vascular development

Abstract

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.