title: klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis.
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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Emily
authors.initials: E
authors.lastname: Steed
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faggianelli
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roth
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ramspacher
authors.affiliation: Muséum National d'Histoire Naturelle, 75231 Paris Cedex 05, France.|CNRS UMR 7196, 75231 Paris Cedex 05, France.|INSERM U1154, 75231 Paris Cedex 05, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Concordet
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67404, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch 67404, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch 67404, France.|Université de Strasbourg, Illkirch 67404, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Vermot
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D020869:Gene Expression Profiling; D006351:Heart Valves / Q000196:embryology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D005353:Fibronectins; C000628305:Fn1b protein, zebrafish; C436494:Klf2a protein, zebrafish; D051741:Kruppel-Like Transcription Factors; D029961:Zebrafish Proteins