1. Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis
- Author
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Julien Vermot, Anne-Laure Duchemin, Hélène Vignes, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 682938 - EVALVE, univOAK, Archive ouverte, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and European Research Council
- Subjects
Life Sciences & Biomedicine - Other Topics ,0301 basic medicine ,0601 Biochemistry and Cell Biology ,Ion Channels ,Mechanobiology ,0302 clinical medicine ,Sciences du Vivant [q-bio]/Biologie cellulaire ,Mechanotransduction ,Biology (General) ,Zebrafish ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,biology ,Receptors, Notch ,Chemistry ,General Neuroscience ,cardiogenesis ,General Medicine ,Heart Valves ,MECHANOBIOLOGY ,Cell biology ,DIFFERENTIATION ,medicine.anatomical_structure ,HEART ,Medicine ,Mechanosensitive channels ,Life Sciences & Biomedicine ,FORM ,Signal Transduction ,Research Article ,EXPRESSION ,TUNA THUNNUS-ALBACARES ,QH301-705.5 ,Science ,Morphogenesis ,Notch signaling pathway ,Kruppel-Like Transcription Factors ,morphogenesis ,General Biochemistry, Genetics and Molecular Biology ,BULBUS ARTERIOSUS ,03 medical and health sciences ,REVEALS ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,Animals ,Heart valve ,Biology ,mechanotransduction ,Science & Technology ,General Immunology and Microbiology ,Mechanosensation ,Sciences du Vivant [q-bio]/Biologie du développement ,YAP-Signaling Proteins ,Zebrafish Proteins ,biology.organism_classification ,030104 developmental biology ,TRPV4 ,Trans-Activators ,Stress, Mechanical ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Mechanical forces are well known for modulating heart valve developmental programs. Yet, it is still unclear how genetic programs and mechanosensation interact during heart valve development. Here, we assessed the mechanosensitive pathways involved during zebrafish outflow tract (OFT) valve development in vivo. Our results show that the hippo effector Yap1, Klf2, and the Notch signaling pathway are all essential for OFT valve morphogenesis in response to mechanical forces, albeit active in different cell layers. Furthermore, we show that Piezo and TRP mechanosensitive channels are important factors modulating these pathways. In addition, live reporters reveal that Piezo controls Klf2 and Notch activity in the endothelium and Yap1 localization in the smooth muscle progenitors to coordinate OFT valve morphogenesis. Together, this work identifies a unique morphogenetic program during OFT valve formation and places Piezo as a central modulator of the cell response to forces in this process. journal article research support, non-u.s. gov't 2019 09 16 2019 09 16 imported
- Published
- 2019
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