ZFIN ID: ZDB-PUB-170523-5
Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues
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.
Date: 2017
Source: Nature cell biology   19(6): 653-665 (Journal)
Registered Authors: Bussmann, Jeroen, Herzog, Wiebke, Siekmann, Arndt Friedrich
Keywords: none
MeSH Terms:
  • Animals
  • Arteriovenous Malformations/genetics
  • Arteriovenous Malformations/metabolism
  • Arteriovenous Malformations/physiopathology
  • Cell Shape*
  • Endoglin/deficiency
  • Endoglin/genetics
  • Endoglin/metabolism*
  • Endothelial Cells/metabolism*
  • Genetic Predisposition to Disease
  • Hemodynamics*
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Kruppel-Like Transcription Factors/genetics
  • Kruppel-Like Transcription Factors/metabolism
  • Mechanotransduction, Cellular*
  • Mice, Knockout
  • Mutation
  • Neovascularization, Physiologic
  • Phenotype
  • Regional Blood Flow
  • Stress, Mechanical
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28530658 Full text @ Nat. Cell Biol.
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.