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 and Tzung K. Hsiai ()
Additional contact information
Jing Wang: University of California, Los Angeles
Aaron L. Brown: Stanford University
Seul-Ki Park: University of California, Los Angeles
Charlie Z. Zheng: University of California, Los Angeles
Adam Langenbacher: University of California, Los Angeles
Enbo Zhu: University of California, Los Angeles
Ryan O’Donnell: University of California, Los Angeles
Peng Zhao: University of California, Los Angeles
Jeffrey J. Hsu: University of California, Los Angeles
Tomohiro Yokota: University of California, Los Angeles
Jiandong Liu: University of North Carolina at Chapel Hill
Jau-Nian Chen: University of California, Los Angeles
Alison L. Marsden: Stanford University
Tzung K. Hsiai: University of California, Los Angeles

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62285-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62285-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62285-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().