The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling
- Max Planck Institute for Heart and Lung Research, Germany
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.
Data availability
The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files. Microarray data have been deposited in GEO under accession number GSE122137.
Article and author information
Author details
Ayele Taddese Tsedeke
Funding
The Leducq Foundation
- Didier Y Stainier
Max-Planck-Gesellschaft (Open-access funding)
- Didier Y Stainier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experimentation: All animal experiments were done in accordance with institutional (MPG) and national ethical and animal welfare guidelines approved by the ethics committee for animal experiments at the Regierungspräsidium Darmstadt, Germany (permit numbers B2/1017, B2/1041, B2/1138 and B2/Anz. 1007).
Reviewing Editor
- Deborah Yelon, University of California, San Diego, United States
Publication history
- Received: June 4, 2018
- Accepted: December 24, 2018
- Accepted Manuscript published: December 28, 2018 (version 1)
- Version of Record published: January 11, 2019 (version 2)
Copyright
© 2018, Rasouli et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling
eLife 7:e38889.
https://doi.org/10.7554/eLife.38889
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