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, and while single mutants exhibit no obvious phenotypes, 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, can rescue 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 leads to abluminal cardiomyocyte extrusion. These studies provide new insights into how Klf2 regulates cardiovascular development and specifically myocardial wall integrity. Examination of transcriptional adaptation of klf2 mutants compared to wild type in zebrafish hearts (1 sample each). To further understand how klf2 regulate cardiac wall integrity, we carried out transcriptomic analysis (using whole genome microarray expression profiling) of klf2 mutant hearts compared to WT. 96 hpf hearts were extracted from klf2 WT and mutant larvae (500 hearts from each genotype) as previously described (Burns & MacRae, 2006)