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
  • 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*
(all 28)
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
Marker Marker Type Name
ak1GENEadenylate kinase 1
astn2GENEastrotactin 2
engGENEendoglin
fli1GENEFli-1 proto-oncogene, ETS transcription factor
gpsm1aGENEG protein signaling modulator 1a
gpsm1bGENEG protein signaling modulator 1b
klf2aGENEKruppel like factor 2a
mitfaGENEmelanocyte inducing transcription factor a
mpv17GENEmitochondrial inner membrane protein MPV17
myl4GENEmyosin, light chain 4, alkali; atrial, embryonic
1 - 10 of 14
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Figures
No images available
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment: nifedipineLong-pec
engmu130/+standard conditionsPrim-15 to Long-pec
engmu130/+standard conditionsPrim-15 to Long-pec
engmu130/+standard conditionsPrim-15 to Long-pec
engmu130/mu130standard conditionsPrim-5 to Long-pec
engmu130/mu130standard conditionsPrim-15 to Long-pec
engmu130/mu130standard conditionsPrim-15 to Long-pec
engmu130/mu130standard conditionsPrim-15 to Long-pec
engmu130/mu130standard conditionsProtruding-mouth
engmu130/mu130standard conditionsProtruding-mouth
1 - 10 of 46
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a9
    		Complex
    hu5333TgTransgenic Insertion
      mu106TgTransgenic Insertion
        mu107TgTransgenic Insertion
          mu130
            		Small Deletion
            mu131
              		Small Deletion
              mu132
                		MNV
                mu156TgTransgenic Insertion
                  mu240TgTransgenic Insertion
                    nkuasgfp1aTgTransgenic Insertion
                      1 - 10 of 16
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      engTALEN1-engTALEN
                      tnnt2aMO1-tnnt2aMRPHLNO
                      1 - 2 of 2
                      Show
                      Fish
                      Fish
                      engmu130/mu130
                      engmu130/mu130; hu5333Tg; mu240Tg; y7Tg
                      engmu130/mu130; mu107Tg; s916Tg
                      engmu130/mu130; mu156Tg
                      engmu130/mu130; mu240Tg; y7Tg
                      engmu130/mu130; s843Tg; sd2Tg
                      engmu130/+
                      engmu130; s916Tg; y1Tg
                      engmu132/mu132
                      engmu132/+
                      1 - 10 of 18
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                      Antibodies
                      Orthology
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      mCherryEFGmCherry
                      RFPEFGRFP
                      YFPEFGYFP
                      1 - 7 of 7
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                      Mapping
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                      Citation
                      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. (2017) Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues. Nature cell biology. 19(6):653-665.