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klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis

Author

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  • Emily Steed

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Nathalie Faggianelli

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Stéphane Roth

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Caroline Ramspacher

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Jean-Paul Concordet

    (Muséum National d'Histoire Naturelle
    CNRS UMR 7196
    INSERM U1154)

  • Julien Vermot

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

Abstract

The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis.

Suggested Citation

  • Emily Steed & Nathalie Faggianelli & Stéphane Roth & Caroline Ramspacher & Jean-Paul Concordet & Julien Vermot, 2016. "klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11646
    DOI: 10.1038/ncomms11646
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    Cited by:

    1. Thomas Juan & Agatha Ribeiro da Silva & Bárbara Cardoso & SoEun Lim & Violette Charteau & Didier Y. R. Stainier, 2023. "Multiple pkd and piezo gene family members are required for atrioventricular valve formation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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