PUBLICATION

Endothelial Cell Self-fusion during Vascular Pruning

Authors
Lenard, A., Daetwyler, S., Betz, C., Ellertsdottir, E., Belting, H.G., Huisken, J., Affolter, M.
ID
ZDB-PUB-150418-3
Date
2015
Source
PLoS Biology   13(4): e1002126 (Journal)
Registered Authors
Affolter, Markus, Belting, Heinz-Georg Paul (Henry), Ellertsdottir, Elin, Huisken, Jan, Lenard, Anna
Keywords
SIV, Embryos, Blood vessels, Endothelial cells, Cell fusion, Blood flow, Cell membranes, Zebrafish
MeSH Terms
  • Zebrafish/embryology
  • Animals, Genetically Modified
  • Neovascularization, Physiologic
  • Animals
  • Cell Fusion*
  • Endothelium, Vascular/embryology*
(all 6)
PubMed
25884426 Full text @ PLoS Biol.
Abstract
During embryonic development, vascular networks remodel to meet the increasing demand of growing tissues for oxygen and nutrients. This is achieved by the pruning of redundant blood vessel segments, which then allows more efficient blood flow patterns. Because of the lack of an in vivo system suitable for high-resolution live imaging, the dynamics of the pruning process have not been described in detail. Here, we present the subintestinal vein (SIV) plexus of the zebrafish embryo as a novel model to study pruning at the cellular level. We show that blood vessel regression is a coordinated process of cell rearrangements involving lumen collapse and cell-cell contact resolution. Interestingly, the cellular rearrangements during pruning resemble endothelial cell behavior during vessel fusion in a reversed order. In pruning segments, endothelial cells first migrate toward opposing sides where they join the parental vascular branches, thus remodeling the multicellular segment into a unicellular connection. Often, the lumen is maintained throughout this process, and transient unicellular tubes form through cell self-fusion. In a second step, the unicellular connection is resolved unilaterally, and the pruning cell rejoins the opposing branch. Thus, we show for the first time that various cellular activities are coordinated to achieve blood vessel pruning and define two different morphogenetic pathways, which are selected by the flow environment.
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nkuasrfp1aTgTransgenic Insertion
    rk7TgTransgenic Insertion
      ubs1TgTransgenic Insertion
        ubs2TgTransgenic Insertion
          ubs3TgTransgenic Insertion
            ubs4TgTransgenic Insertion
              ubs5TgTransgenic Insertion
                ubs12TgTransgenic Insertion
                  ubs16TgTransgenic Insertion
                    y1TgTransgenic Insertion
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                      tnnt2aMO1-tnnt2aMRPHLNO
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                      Fish
                      Fish
                      nkuasrfp1aTg; ubs4Tg; ubs5Tg
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                      ubs1Tg
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                      ubs3Tg
                      ubs4Tg
                      ubs5Tg
                      ubs12Tg
                      ubs16Tg
                      y1Tg
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                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      KaedeEFGKaede
                      mKate2EFGmKate2
                      RFPEFGRFP
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                      Citation
                      Lenard, A., Daetwyler, S., Betz, C., Ellertsdottir, E., Belting, H.G., Huisken, J., Affolter, M. (2015) Endothelial Cell Self-fusion during Vascular Pruning. PLoS Biology. 13(4):e1002126.