ZFIN ID: ZDB-PUB-181230-7
The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling
Rasouli, S.J., El-Brolosy, M., Tsedeke, A.T., Bensimon-Brito, A., Ghanbari, P., Maischein, H.M., Kuenne, C., Stainier, D.Y.
Date: 2018
Source: eLIFE   7: (Journal)
Registered Authors: Maischein, Hans-Martin, Stainier, Didier
Keywords: developmental biology, zebrafish
Microarrays: 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
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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.
ADDITIONAL INFORMATION