PUBLICATION

sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation

Authors
Lawson, N.D., Vogel, A.M., and Weinstein, B.M.
ID
ZDB-PUB-020820-6
Date
2002
Source
Developmental Cell   3(1): 127-136 (Journal)
Registered Authors
Lawson, Nathan, Vogel, Andreas M., Weinstein, Brant M.
Keywords
none
MeSH Terms
  • Trans-Activators/metabolism*
  • Zebrafish
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology*
  • Embryo, Nonmammalian/metabolism
  • Receptors, Notch
  • Lymphokines/metabolism*
  • Vascular Endothelial Growth Factor A
  • Signal Transduction/physiology
  • Gene Expression Regulation, Developmental/physiology
  • Endothelial Growth Factors/metabolism*
  • Vascular Endothelial Growth Factors
  • Arteries/cytology
  • Arteries/embryology*
  • Arteries/metabolism
  • Cell Differentiation/physiology*
  • Body Patterning/physiology
  • Animals
  • Hedgehog Proteins
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/embryology*
  • Endothelium, Vascular/metabolism
  • Membrane Proteins/metabolism*
PubMed
12110173 Full text @ Dev. Cell
Abstract
The appearance of molecular differences between arterial and venous endothelial cells before circulation suggests that genetic factors determine these cell types. We find that vascular endothelial growth factor (vegf) acts downstream of sonic hedgehog (shh) and upstream of the Notch pathway to determine arterial cell fate. Loss of Vegf or Shh results in loss of arterial identity, while exogenous expression of these factors causes ectopic expression of arterial markers. Microinjection of vegf mRNA into embryos lacking Shh activity can rescue arterial differentiation. Finally, activation of the Notch pathway in the absence of Vegf signaling can rescue arterial marker gene expression . These studies reveal a complex signaling cascade responsible for establishing arterial cell fate and suggest differential effects of Vegf on developing endothelial cells.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping