Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation
- Jing Wang
- Aaron L. Brown
- Seul-Ki Park
- Charlie Z. Zheng
- Adam Langenbacher
- Enbo Zhu
- Ryan O’Donnell
- Peng Zhao
- Jeffrey J. Hsu
- Tomohiro Yokota
- Jiandong Liu
- Jau-Nian Chen
- Alison L. Marsden
- Tzung K. Hsiai
2025-09-24
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 the myocardial strain along radial trabecular ridges in alignment with the snai1b expression and Notch-ErbB2-mediated trabeculation. Single-cell and spatial transcriptomics reveal that these snai1b -positive cardiomyocytes are devoid of some epithelial-to-mesenchymal transition-related phenotypes, such as Col1a2 production and induction by ErbB2 or TGF-β. Thus, we uncover snai1b -positive cardiomyocytes that are mechanically activated to initiate delamination for cardiac trabeculation.