1. klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis
- Author
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Nathalie Faggianelli, Emily Steed, Julien Vermot, Jean-Paul Concordet, Caroline Ramspacher, Stéphane Roth, 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), Structure et Instabilité des Génomes (STRING), and Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Heart valve morphogenesis ,Science ,Morphogenesis ,Kruppel-Like Transcription Factors ,General Physics and Astronomy ,Biology ,Mechanotransduction, Cellular ,General Biochemistry, Genetics and Molecular Biology ,Article ,Animals, Genetically Modified ,03 medical and health sciences ,Leaflet formation ,Live cell imaging ,medicine ,Animals ,Mechanotransduction ,Zebrafish ,Multidisciplinary ,Heart valve formation ,Gene Expression Profiling ,[SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis ,General Chemistry ,Anatomy ,Zebrafish Proteins ,biology.organism_classification ,Heart Valves ,3. Good health ,Cell biology ,Extracellular Matrix ,Fibronectins ,030104 developmental biology ,medicine.anatomical_structure ,Ventricle - 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., In the developing heart, blood flow transmits mechanical signals to progenitor cells that ultimately leads to valve formation. Here, the authors identify the origin of the valve progenitor cells and fibronectin1b as a transcriptional target of the mechanotransduced signals responsible for valve formation.
- Published
- 2016
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