PUBLICATION

The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling

Authors
Rasouli, S.J., El-Brolosy, M., Tsedeke, A.T., Bensimon-Brito, A., Ghanbari, P., Maischein, H.M., Kuenne, C., Stainier, D.Y.
ID
ZDB-PUB-181230-7
Date
2018
Source
eLIFE   7: (Journal)
Registered Authors
Bensimon-Brito, Anabela, Maischein, Hans-Martin, Stainier, Didier
Keywords
developmental biology, zebrafish
Datasets
GEO:GSE122137
MeSH Terms
  • Phenotype
  • Cadherins/metabolism
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Fibroblast Growth Factors/metabolism*
  • Cell Polarity
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Down-Regulation
  • Base Sequence
  • Myocardial Contraction
  • Hedgehog Proteins/metabolism
  • Mutation/genetics
  • Signal Transduction*
  • Gene Expression Regulation, Developmental
  • Tretinoin/metabolism
  • Ligands
  • Receptors, Fibroblast Growth Factor/metabolism
  • Kruppel-Like Transcription Factors/genetics
  • Kruppel-Like Transcription Factors/metabolism*
  • Phosphorylation
  • Alleles
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Cell Death
  • Animals
  • Embryo, Nonmammalian/metabolism
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Cell Proliferation
(all 34)
PubMed
30592462 Full text @ Elife
Abstract
Complex interplay between cardiac tissues is crucial for their integrity. The flow responsive transcription factor KLF2, which is expressed in the endocardium, is vital for cardiovascular development but its exact role remains to be defined. To this end, we mutated both klf2 paralogues in zebrafish, and while single mutants exhibit no obvious phenotype, double mutants display a novel phenotype of cardiomyocyte extrusion towards the abluminal side. This extrusion requires cardiac contractility and correlates with the mislocalization of N-cadherin from the lateral to the apical side of cardiomyocytes. Transgenic rescue data show that klf2 expression in endothelium, but not myocardium, prevents this cardiomyocyte extrusion phenotype. Transcriptome analysis of klf2 mutant hearts reveals that Fgf signaling is affected, and accordingly, we find that inhibition of Fgf signaling in wild-type animals can lead to abluminal cardiomyocyte extrusion. These studies provide new insights into how Klf2 regulates cardiovascular development and specifically myocardial wall integrity.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
bns7TgTransgenic Insertion
    bns11
      Small Deletion
      bns12
        Small Deletion
        bns197TgTransgenic Insertion
          bns200TgTransgenic Insertion
            bns234TgTransgenic Insertion
              bns235TgTransgenic Insertion
                ci1TgTransgenic Insertion
                  hsc4TgTransgenic Insertion
                    ncv43TgTransgenic Insertion
                      1 - 10 of 17
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      cdh2MO1-cdh2MRPHLNO
                      klf2aTALEN3-klf2aTALEN
                      klf2bTALEN1-klf2bTALEN
                      myh6MO1-myh6MRPHLNO
                      tnnt2aMO1-tnnt2aMRPHLNO
                      1 - 5 of 5
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                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-cav1polyclonal
                        Rabbit
                        Ab9-mapkmonoclonal
                          IgGRabbit
                          1 - 2 of 2
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                          Orthology
                          No data available
                          Engineered Foreign Genes
                          Marker Marker Type Name
                          DsRedxEFGDsRedx
                          ECFPEFGECFP
                          EGFPEFGEGFP
                          GFPEFGGFP
                          mCherryEFGmCherry
                          mKate2EFGmKate2
                          NTREFGNTR
                          TomatoEFGTomato
                          VenusEFGVenus
                          1 - 9 of 9
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                          Mapping
                          No data available