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The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling
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,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329608/ https://www.ncbi.nlm.nih.gov/pubmed/30592462 http://dx.doi.org/10.7554/eLife.38889 |
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author | Rasouli, Seyed Javad El-Brolosy, Mohamed Tsedeke, Ayele Taddese Bensimon-Brito, Anabela Ghanbari, Parisa Maischein, Hans-Martin Kuenne, Carsten Stainier, Didier Y |
author_facet | Rasouli, Seyed Javad El-Brolosy, Mohamed Tsedeke, Ayele Taddese Bensimon-Brito, Anabela Ghanbari, Parisa Maischein, Hans-Martin Kuenne, Carsten Stainier, Didier Y |
author_sort | Rasouli, Seyed Javad |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6329608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63296082019-01-14 The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling Rasouli, Seyed Javad El-Brolosy, Mohamed Tsedeke, Ayele Taddese Bensimon-Brito, Anabela Ghanbari, Parisa Maischein, Hans-Martin Kuenne, Carsten Stainier, Didier Y eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2018-12-28 /pmc/articles/PMC6329608/ /pubmed/30592462 http://dx.doi.org/10.7554/eLife.38889 Text en © 2018, Rasouli et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Rasouli, Seyed Javad El-Brolosy, Mohamed Tsedeke, Ayele Taddese Bensimon-Brito, Anabela Ghanbari, Parisa Maischein, Hans-Martin Kuenne, Carsten Stainier, Didier Y The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling |
title | The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling |
title_full | The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling |
title_fullStr | The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling |
title_full_unstemmed | The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling |
title_short | The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling |
title_sort | flow responsive transcription factor klf2 is required for myocardial wall integrity by modulating fgf signaling |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329608/ https://www.ncbi.nlm.nih.gov/pubmed/30592462 http://dx.doi.org/10.7554/eLife.38889 |
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