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
  • Alleles
  • Animals
  • Base Sequence
  • Cadherins/metabolism
  • Cell Death
  • Cell Polarity
  • Cell Proliferation
  • Down-Regulation
  • Embryo, Nonmammalian/metabolism
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins/metabolism
  • Kruppel-Like Transcription Factors/genetics
  • Kruppel-Like Transcription Factors/metabolism*
  • Ligands
  • Mutation/genetics
  • Myocardial Contraction
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Phenotype
  • Phosphorylation
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Fibroblast Growth Factor/metabolism
  • Signal Transduction*
  • Tretinoin/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
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
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping