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01-09-2009 | Special Issue on Cardiovascular Development

Regulation of endothelial cell differentiation and arterial specification by VEGF and Notch signaling

Author: Masanori Hirashima

Published in: Anatomical Science International | Issue 3/2009

Abstract

Analysis of molecular and cellular mechanisms underlying vascular development in vertebrates indicates that initially vasculogenesis occurs when a primary capillary plexus forms de novo from endothelial cell precursors derived from nascent mesodermal cells. Transplantation experiments in avian embryos demonstrate that embryonic endothelial cells originate from two different mesodermal lineages: splanchnic mesoderm and somites. Genetic analysis of mouse and zebrafish reveals that vascular endothelial growth factor (VEGF)/Flk1 and Notch signaling play crucial roles throughout embryonic vascular development. VEGFA plays a major role in endothelial cell proliferation, migration, survival, and regulation of vascular permeability. Flk1, the primary VEGFA receptor, is the earliest marker of the developing endothelial lineage and is essential for endothelial differentiation during vasculogenesis. Notch signaling has been demonstrated to directly induce arterial endothelial differentiation. Recent studies suggest that Notch signaling is activated downstream of VEGF signaling and negatively regulates VEGF-induced angiogenesis and suppresses aberrant vascular branching morphogenesis. In addition to altering endothelial cell fate through Notch activation, VEGFA directly guides endothelial cell migration in an isoform-dependent manner, modifying vascular patterns. Interestingly, genetic studies in mice show that many molecules involved in VEGF or Notch signaling must be tightly regulated for proper vascular formation. Taken together, VEGF and Notch signaling apparently coordinate vascular patterning by regulating each other.

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Title: Regulation of endothelial cell differentiation and arterial specification by VEGF and Notch signaling
Author: Masanori Hirashima
Publication date: 01-09-2009
Publisher: Springer Japan
Published in: Anatomical Science International / Issue 3/2009
Print ISSN: 1447-6959
Electronic ISSN: 1447-073X
DOI: https://doi.org/10.1007/s12565-009-0026-1

At a glance: The STEP trials

Springer Medicine

Regulation of endothelial cell differentiation and arterial specification by VEGF and Notch signaling

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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