PUBLICATION

Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues

Authors
Sugden, W.W., Meissner, R., Aegerter-Wilmsen, T., Tsaryk, R., Leonard, E.V., Bussmann, J., Hamm, M.J., Herzog, W., Jin, Y., Jakobsson, L., Denz, C., Siekmann, A.F.
ID
ZDB-PUB-170523-5
Date
2017
Source
Nature cell biology   19(6): 653-665 (Journal)
Registered Authors
Bussmann, Jeroen, Herzog, Wiebke, Siekmann, Arndt Friedrich
Keywords
none
MeSH Terms
  • Hemodynamics*
  • Phenotype
  • Genetic Predisposition to Disease
  • Arteriovenous Malformations/genetics
  • Arteriovenous Malformations/metabolism
  • Arteriovenous Malformations/physiopathology
  • Mutation
  • Mice, Knockout
  • Time Factors
  • Endoglin/deficiency
  • Endoglin/genetics
  • Endoglin/metabolism*
  • Kruppel-Like Transcription Factors/genetics
  • Kruppel-Like Transcription Factors/metabolism
  • Humans
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Endothelial Cells/metabolism*
  • Stress, Mechanical
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Animals
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Mechanotransduction, Cellular*
  • Cell Shape*
  • Regional Blood Flow
  • Neovascularization, Physiologic
PubMed
28530658 Full text @ Nat. Cell Biol.
Abstract
The hierarchical organization of properly sized blood vessels ensures the correct distribution of blood to all organs of the body, and is controlled via haemodynamic cues. In current concepts, an endothelium-dependent shear stress set point causes blood vessel enlargement in response to higher flow rates, while lower flow would lead to blood vessel narrowing, thereby establishing homeostasis. We show that during zebrafish embryonic development increases in flow, after an initial expansion of blood vessel diameters, eventually lead to vessel contraction. This is mediated via endothelial cell shape changes. We identify the transforming growth factor beta co-receptor endoglin as an important player in this process. Endoglin mutant cells and blood vessels continue to enlarge in response to flow increases, thus exacerbating pre-existing embryonic arterial-venous shunts. Together, our data suggest that cell shape changes in response to biophysical cues act as an underlying principle allowing for the ordered patterning of tubular organs.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping