biostudies-literatureWang JNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)8363https://www.ebi.ac.uk/biostudies/studies/S-EPMC12460811biostudies-literatureUnknown16(1)During development, myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation. While Snail family genes are well-recognized transcription factors of epithelial-to-mesenchymal transition, snai1b-positive cardiomyocytes are sparsely distributed in the ventricle of zebrafish at 4 days post-fertilization. Isoproterenol treatment significantly increases the number of snai1b-positive cardiomyocytes, of which 80% are Notch-negative. CRISPR-activation of snai1b leads to 51.6% cardiomyocytes forming trabeculae, whereas CRISPR-repression reduces trabecular cardiomyocytes to 6.7% under isoproterenol. In addition, 36.7% of snai1b-repressed cardiomyocytes undergo apical delamination. 4-D strain analysis demonstrates that isoproterenol increases thNature communicationsMechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation.PMC12460811R01HL159970T32HL144449R01 HL159970R01 HL129727R01 HL165318T32 HL144449R01HL165318R01HL129727Liu JO'Donnell RHsiai TKBrown ALLangenbacher AZhu EWang JChen JNMarsden ALZheng CZHsu JJZhao PPark SKYokota TfalseMechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation.During development, myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation. While Snail family genes are well-recognized transcription factors of epithelial-to-mesenchymal transition, snai1b-positive cardiomyocytes are sparsely distributed in the ventricle of zebrafish at 4 days post-fertilization. Isoproterenol treatment significantly increases the number of snai1b-positive cardiomyocytes, of which 80% are Notch-negative. CRISPR-activation of snai1b leads to 51.6% cardiomyocytes forming trabeculae, whereas CRISPR-repression reduces trabecular cardiomyocytes to 6.7% under isoproterenol. In addition, 36.7% of snai1b-repressed cardiomyocytes undergo apical delamination. 4-D strain analysis demonstrates that isoproterenol increases th2025-01-01T00:00:00Z2025 Sep2026-07-15T09:49:00.7Z2026-07-02T03:12:09.877ZS-EPMC124608114099314910.1038/s41467-025-62285-w