PUBLICATION

Vegfa signals through ERK to promote angiogenesis, but not artery differentiation

Authors
Shin, M., Beane, T., Quillien, A., Male, I., Zhu, L.J., Lawson, N.D.
ID
ZDB-PUB-160901-3
Date
2016
Source
Development (Cambridge, England)   143(20): 3796-3805 (Journal)
Registered Authors
Lawson, Nathan, Shin, Masahiro
Keywords
ERK, Vegfa, Angiogenesis, Artery differentiation, Zebrafish
MeSH Terms
  • In Situ Hybridization
  • Blotting, Western
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Arteries/cytology*
  • Arteries/metabolism
  • Cell Differentiation/genetics
  • Cell Differentiation/physiology
  • Signal Transduction/genetics
  • Signal Transduction/physiology
  • Animals
  • Animals, Genetically Modified
  • Zebrafish
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology
  • Extracellular Signal-Regulated MAP Kinases/genetics
  • Extracellular Signal-Regulated MAP Kinases/metabolism*
  • Vascular Endothelial Growth Factor Receptor-3/genetics
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
(all 21)
PubMed
27578780 Full text @ Development
Abstract
Vascular endothelial growth factor a (Vegfa) is essential for blood vessel formation and can induce activation of numerous signaling effectors in endothelial cells. However, it is unclear how and where these function in developmental contexts during vascular morphogenesis. To address this issue, we have visualized activation of presumptive Vegfa effectors at single cell resolution in zebrafish blood vessels. From these studies, we find that phosphorylation of the serine/threonine kinase ERK (pERK) preferentially occurs in endothelial cells undergoing angiogenesis, but not in committed arterial endothelial cells. pERK in endothelial cells was ectopically induced by Vegfa and lost in Vegfa signaling mutants. Both chemical and endothelial autonomous inhibition of ERK prevented endothelial sprouting, but did not prevent initial artery differentiation. Timed chemical inhibition during angiogenesis caused a loss of genes implicated in coordinating tip/stalk cell behaviors, including flt4 and, at later stages, dll4 ERK inhibition also blocked excessive angiogenesis and ectopic flt4 expression in Notch-deficient blood vessels. Together, these studies implicate ERK as a specific effector of Vegfa signaling in the induction of angiogenic genes during sprouting.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
la116TgTransgenic Insertion
    mu101TgTransgenic Insertion
      nkuasgfp1aTgTransgenic Insertion
        ta52b
          Point Mutation
          um19
            Small Deletion
            um131
              Indel
              um151TgTransgenic Insertion
                um152TgTransgenic Insertion
                  y1TgTransgenic Insertion
                    y13
                      Point Mutation
                      1 - 10 of 11
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      dll4MO2-dll4MRPHLNO
                      1 - 1 of 1
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      GFPEFGGFP
                      TomatoEFGTomato
                      1 - 4 of 4
                      Show
                      Mapping
                      No data available