PUBLICATION

Zebrafish mutants in vegfab can affect endothelial cell proliferation without altering ERK phosphorylation and are phenocopied by loss of PI3K signaling

Authors
Lange, M., Ohnesorge, N., Hoffmann, D., Rocha, S.F., Benedito, R., Siekmann, A.F.
ID
ZDB-PUB-220327-9
Date
2022
Source
Developmental Biology   486: 26-43 (Journal)
Registered Authors
Hoffmann, Dennis, Siekmann, Arndt Friedrich
Keywords
Angiogenesis, Endothelial cell proliferation, PI3 kinase signaling, Vegf signaling, Zebrafish
MeSH Terms
  • Animals
  • Cell Proliferation
  • Neovascularization, Physiologic/genetics
  • Phenotype
  • Phosphatidylinositol 3-Kinases/genetics
  • Phosphatidylinositol 3-Kinases/metabolism
  • Phosphorylation
  • Vascular Endothelial Growth Factor A*/genetics
  • Vascular Endothelial Growth Factor A*/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
35337795 Full text @ Dev. Biol.
Abstract
The formation of appropriately patterned blood vessel networks requires endothelial cell migration and proliferation. Signaling through the Vascular Endothelial Growth Factor A (VEGFA) pathway is instrumental in coordinating these processes. mRNA splicing generates short (diffusible) and long (extracellular matrix bound) Vegfa isoforms. The differences between these isoforms in controlling cellular functions are not understood. In zebrafish, vegfaa generates short and long isoforms, while vegfab only generates long isoforms. We found that mutations in vegfaa had an impact on endothelial cell (EC) migration and proliferation. Surprisingly, mutations in vegfab more strongly affected EC proliferation in distinct blood vessels, such as intersegmental blood vessels in the zebrafish trunk and central arteries in the head. Analysis of downstream signaling pathways revealed no change in MAPK (ERK) activation, while inhibiting PI3 kinase signaling phenocopied vegfab mutant phenotypes in affected blood vessels. Together, these results suggest that extracellular matrix bound Vegfa might act through PI3K signaling to control EC proliferation in a distinct set of blood vessels during angiogenesis.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping