The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression.

Abstract

The transcription factor Snai1, a well-known regulator of epithelial-to-mesenchymal transition, has been implicated in early cardiac morphogenesis as well as in cardiac valve formation. However, a role for Snai1 in regulating other aspects of cardiac morphogenesis has not been reported. Using genetic, transcriptomic, and chimeric analyses in zebrafish, we find that Snai1b is required in cardiomyocytes for myocardial wall integrity. Loss of <i>snai1b</i> increases the frequency of cardiomyocyte extrusion away from the cardiac lumen. Extruding cardiomyocytes exhibit increased actomyosin contractility basally as revealed by enrichment of p-myosin and α-catenin epitope α-18, as well as disrupted intercellular junctions. Transcriptomic analysis of wild-type and <i>snai1b</i> mutant hearts revealed the dysregulation of intermediate filament genes, including <i>desmin b</i> (<i>desmb</i>) upregulation. Cardiomyocyte-specific <i>desmb</i> overexpression caused increased cardiomyocyte extrusion, recapitulating the <i>snai1b</i> mutant phenotype. Altogether, these results indicate that Snai1 maintains the integrity of the myocardial epithelium, at least in part by repressing <i>desmb</i> expression.