The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling.
Elife
; 72018 12 28.
Article
em En
| MEDLINE
| ID: mdl-30592462
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas de Peixe-Zebra
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Fatores de Transcrição Kruppel-Like
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Fatores de Crescimento de Fibroblastos
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Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article