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
-
- Animals
- Animals, Genetically Modified
- Arteries/cytology*
- Arteries/metabolism
- Blotting, Western
- Cell Differentiation/genetics
- Cell Differentiation/physiology
- Extracellular Signal-Regulated MAP Kinases/genetics
- Extracellular Signal-Regulated MAP Kinases/metabolism*
- In Situ Hybridization
- Neovascularization, Physiologic/genetics
- Neovascularization, Physiologic/physiology
- Receptors, Notch/genetics
- Receptors, Notch/metabolism
- Signal Transduction/genetics
- Signal Transduction/physiology
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism*
- Vascular Endothelial Growth Factor Receptor-3/genetics
- Vascular Endothelial Growth Factor Receptor-3/metabolism
- Zebrafish
- PubMed
- 27578780 Full text @ Development
Citation
Shin, M., Beane, T., Quillien, A., Male, I., Zhu, L.J., Lawson, N.D. (2016) Vegfa signals through ERK to promote angiogenesis, but not artery differentiation. Development (Cambridge, England). 143(20):3796-3805.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping