PUBLICATION

The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics

Authors
Wen, L., Zhang, T., Wang, J., Jin, X., Rouf, M.A., Luo, D., Zhu, Y., Lei, D., Gregersen, H., Wang, Y., Wang, G.
ID
ZDB-PUB-210730-6
Date
2021
Source
PLoS Genetics   17: e1009690 (Journal)
Registered Authors
Lei, Daoxi, Luo, Desha, Wang, Guixue, Wen, Lin
Keywords
none
MeSH Terms
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism
  • Muscle Proteins/physiology*
  • Nerve Tissue Proteins/metabolism
  • Nerve Tissue Proteins/physiology*
  • Cell Movement
  • Actin Cytoskeleton/metabolism
  • Actin Cytoskeleton/physiology
  • Capillaries/metabolism
  • Morphogenesis
  • Blood Circulation/physiology*
  • Kruppel-Like Transcription Factors/genetics
  • Microfilament Proteins/genetics
  • Microfilament Proteins/metabolism
  • Microfilament Proteins/physiology*
  • Animals, Genetically Modified
  • Animals
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
  • Endothelial Cells/metabolism
  • Endothelial Cells/physiology
  • Zebrafish/metabolism
  • Zebrafish/physiology
(all 23)
PubMed
34319989 Full text @ PLoS Genet.
Abstract
Recent studies have focused on capillary pruning in various organs and species. However, the way in which large-diameter vessels are pruned remains unclear. Here we show that pruning of the zebrafish caudal vein (CV) from ventral capillaries of the CV plexus in different transgenic embryos is driven by endothelial cell (EC) rearrangement, which involves EC nucleus migration, junction remodeling, and actin cytoskeleton remodeling. Further observation reveals a growing difference in blood flow velocity between the two vessels in CV pruning in zebrafish embryos. With this model, we identify the critical role of Kruppel-like factor 6a (klf6a) in CV pruning. Disruption of klf6a functioning impairs CV pruning in zebrafish. klf6a is required for EC nucleus migration, junction remodeling, and actin cytoskeleton dynamics in zebrafish embryos. Moreover, actin-related protein transgelin 2 (tagln2) is a direct downstream target of klf6a in CV pruning in zebrafish embryos. Together these results demonstrate that the klf6a-tagln2 axis regulates CV pruning by promoting EC rearrangement.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c369TgTransgenic Insertion
    ci5TgTransgenic Insertion
      cqu1
        		Small Deletion
        cqu2TgTransgenic Insertion
        cqu3
          		Small Deletion
          cqu4TgTransgenic Insertion
          cqu5TgTransgenic Insertion
            cqu6TgTransgenic Insertion
              s843TgTransgenic Insertion
                sd2TgTransgenic Insertion
                  1 - 10 of 11
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  cdh5CRISPR5-cdh5CRISPR
                  klf6aCRISPR2-klf6aCRISPR
                  klf6aMO1-klf6aMRPHLNO
                  tagln2CRISPR1-tagln2CRISPR
                  tagln2MO2-tagln2MRPHLNO
                  tnnt2aMO1-tnnt2aMRPHLNO
                  1 - 6 of 6
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                  Fish
                  Fish
                  cdh5cqu2Tg; cqu6Tg
                  cdh5cqu2Tg; cqu6Tg + MO1-klf6a
                  cdh5cqu2Tg; cqu6Tg + MO2-tagln2
                  ci5Tg; y7Tg
                  ci5Tg; y7Tg + MO1-klf6a
                  ci5Tg; y7Tg + MO2-tagln2
                  klf6acqu3/cqu3
                  klf6acqu3/cqu3; s843Tg; sd2Tg
                  klf6acqu4Tg; c369Tg; ci5Tg
                  s843Tg
                  1 - 10 of 13
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                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  DsRedEFGDsRed
                  EGFPEFGEGFP
                  GAL4EFGGAL4
                  GFPEFGGFP
                  mCherryEFGmCherry
                  mRFPEFGmRFP
                  1 - 6 of 6
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                  Mapping
                  No data available
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                  Citation
                  Wen, L., Zhang, T., Wang, J., Jin, X., Rouf, M.A., Luo, D., Zhu, Y., Lei, D., Gregersen, H., Wang, Y., Wang, G. (2021) The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics. PLoS Genetics. 17:e1009690.