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Tension heterogeneity directs form and fate to pattern the myocardial wall

Author

Listed:
  • Rashmi Priya

    (Max Planck Institute for Heart and Lung Research
    German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main)

  • Srinivas Allanki

    (Max Planck Institute for Heart and Lung Research)

  • Alessandra Gentile

    (Max Planck Institute for Heart and Lung Research)

  • Shivani Mansingh

    (Max Planck Institute for Heart and Lung Research)

  • Veronica Uribe

    (Max Planck Institute for Heart and Lung Research
    The University of Melbourne)

  • Hans-Martin Maischein

    (Max Planck Institute for Heart and Lung Research)

  • Didier Y. R. Stainier

    (Max Planck Institute for Heart and Lung Research
    German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main)

Abstract

How diverse cell fates and complex forms emerge and feed back to each other to sculpt functional organs remains unclear. In the developing heart, the myocardium transitions from a simple epithelium to an intricate tissue that consists of distinct layers: the outer compact and inner trabecular layers. Defects in this process, which is known as cardiac trabeculation, cause cardiomyopathies and embryonic lethality, yet how tissue symmetry is broken to specify trabecular cardiomyocytes is unknown. Here we show that local tension heterogeneity drives organ-scale patterning and cell-fate decisions during cardiac trabeculation in zebrafish. Proliferation-induced cellular crowding at the tissue scale triggers tension heterogeneity among cardiomyocytes of the compact layer and drives those with higher contractility to delaminate and seed the trabecular layer. Experimentally, increasing crowding within the compact layer cardiomyocytes augments delamination, whereas decreasing it abrogates delamination. Using genetic mosaics in trabeculation-deficient zebrafish models—that is, in the absence of critical upstream signals such as Nrg–Erbb2 or blood flow—we find that inducing actomyosin contractility rescues cardiomyocyte delamination and is sufficient to drive cardiomyocyte fate specification, as assessed by Notch reporter expression in compact layer cardiomyocytes. Furthermore, Notch signalling perturbs the actomyosin machinery in cardiomyocytes to restrict excessive delamination, thereby preserving the architecture of the myocardial wall. Thus, tissue-scale forces converge on local cellular mechanics to generate complex forms and modulate cell-fate choices, and these multiscale regulatory interactions ensure robust self-organized organ patterning.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:nature:v:588:y:2020:i:7836:d:10.1038_s41586-020-2946-9
    DOI: 10.1038/s41586-020-2946-9
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    Cited by:

    1. Marga Albu & Eileen Affolter & Alessandra Gentile & Yanli Xu & Khrievono Kikhi & Sarah Howard & Carsten Kuenne & Rashmi Priya & Felix Gunawan & Didier Y. R. Stainier, 2024. "Distinct mechanisms regulate ventricular and atrial chamber wall formation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Dorothee Bornhorst & Amulya V. Hejjaji & Lena Steuter & Nicole M. Woodhead & Paul Maier & Alessandra Gentile & Alice Alhajkadour & Octavia Santis Larrain & Michael Weber & Khrievono Kikhi & Stefan Gue, 2024. "The heart is a resident tissue for hematopoietic stem and progenitor cells in zebrafish," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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