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

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 snai1b 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 alpha-catenin epitope alpha-18, as well as disrupted intercellular junctions. Transcriptomic analysis of wild-type and snai1b mutant hearts revealed the dysregulation of intermediate filament genes, including desmin b (desmb) upregulation. Cardiomyocyte-specific desmb overexpression caused increased cardiomyocyte extrusion, recapitulating the snai1b mutant phenotype. Altogether, these results indicate that Snai1 maintains the integrity of the myocardial epithelium, at least in part by repressing desmb expression.

Automated summary

The transcription factor Snai1b is crucial for maintaining myocardial wall integrity in cardiomyocytes by repressing desmin b expression. Loss of Snai1b leads to increased extrusion of cardiomyocytes and enhanced actomyosin contractility. These findings underscore the importance of Snai1 in regulating cardiac morphogenesis beyond its known roles in epithelial-to-mesenchymal transition and cardiac valve formation.