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Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation

Author

Listed:
  • Jing Wang

    (University of California, Los Angeles)

  • Aaron L. Brown

    (Stanford University)

  • Seul-Ki Park

    (University of California, Los Angeles
    Greater Los Angeles Veteran Affairs Healthcare System)

  • Charlie Z. Zheng

    (University of California, Los Angeles)

  • Adam Langenbacher

    (University of California, Los Angeles)

  • Enbo Zhu

    (University of California, Los Angeles
    Greater Los Angeles Veteran Affairs Healthcare System)

  • Ryan O’Donnell

    (University of California, Los Angeles)

  • Peng Zhao

    (University of California, Los Angeles
    Greater Los Angeles Veteran Affairs Healthcare System)

  • Jeffrey J. Hsu

    (University of California, Los Angeles)

  • Tomohiro Yokota

    (University of California, Los Angeles
    Greater Los Angeles Veteran Affairs Healthcare System)

  • 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
    University of California, Los Angeles
    Greater Los Angeles Veteran Affairs Healthcare System)

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.

Suggested Citation

  • 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. M, 2025. "Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62285-w
    DOI: 10.1038/s41467-025-62285-w
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    References listed on IDEAS

    as
    1. Rashmi Priya & Srinivas Allanki & Alessandra Gentile & Shivani Mansingh & Veronica Uribe & Hans-Martin Maischein & Didier Y. R. Stainier, 2020. "Tension heterogeneity directs form and fate to pattern the myocardial wall," Nature, Nature, vol. 588(7836), pages 130-134, December.
    2. Xueying Tian & Yan Li & Lingjuan He & Hui Zhang & Xiuzhen Huang & Qiaozhen Liu & Wenjuan Pu & Libo Zhang & Yi Li & Huan Zhao & Zhifu Wang & Jianhong Zhu & Yu Nie & Shengshou Hu & David Sedmera & Tao P, 2017. "Identification of a hybrid myocardial zone in the mammalian heart after birth," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    3. Peidong Han & Joshua Bloomekatz & Jie Ren & Ruilin Zhang & Jonathan D. Grinstein & Long Zhao & C. Geoffrey Burns & Caroline E. Burns & Ryan M. Anderson & Neil C. Chi, 2016. "Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis," Nature, Nature, vol. 534(7609), pages 700-704, June.
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