PUBLICATION

The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

Authors
Klems, A., van Rijssel, J., Ramms, A.S., Wild, R., Hammer, J., Merkel, M., Derenbach, L., Préau, L., Hinkel, R., Suarez-Martinez, I., Schulte-Merker, S., Vidal, R., Sauer, S., Kivelä, R., Alitalo, K., Kupatt, C., van Buul, J.D., le Noble, F.
ID
ZDB-PUB-201023-4
Date
2020
Source
Nature communications   11: 5319 (Journal)
Registered Authors
Klems, Alina, le Noble, Ferdinand, Préau, Laetitia, Schulte-Merker, Stefan, Wild, Raphael
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Size
  • Cells, Cultured
  • Endothelial Cells/cytology*
  • Endothelial Cells/physiology*
  • Guanine Nucleotide Exchange Factors/genetics
  • Guanine Nucleotide Exchange Factors/physiology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Models, Cardiovascular
  • Placenta Growth Factor/genetics
  • Placenta Growth Factor/physiology
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/physiology
  • Signal Transduction
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/physiology*
  • Vascular Endothelial Growth Factor Receptor-1/genetics
  • Vascular Endothelial Growth Factor Receptor-1/physiology
  • Vascular Remodeling/genetics
  • Vascular Remodeling/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
  • rac1 GTP-Binding Protein/genetics
  • rac1 GTP-Binding Protein/physiology
PubMed
33087700 Full text @ Nat. Commun.
Abstract
Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes