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Actin Dynamics And The Bmp Pathway Drive Apical Extrusion Of Proepicardial Cells

Laura Andrés-Delgado, Alexander Ernst, María Galardi-Castilla, David Bazaga, Marina Peralta, Juliane Münch, Juan Manuel González-Rosa, Inês Marques, Federico Tessadori, José Luis de la Pompa, Julien Vermot, Nadia Mercader

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The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis it arises from the proepicardium (PE), a cell cluster that appears in the dorsal pericardium (DP) close to the venous pole of the heart. Little is known about how the PE emerges from the pericardial mesothelium. Using the zebrafish model and a combination of genetic tools, pharmacological agents and quantitative in vivo imaging, we reveal that a coordinated collective movement of DP cells drives PE formation. We found that BMP signaling and the actomyosin cytoskeleton promote constriction of the DP, which enabled PE cells to extrude apically. We provide evidence that cell extrusion, which has been described in the elimination of unfit cells from epithelia and the emergence of hematopoietic stem cells, is also a mechanism for PE cells to exit an organized mesothelium and fulfil the developmental fate to form a new tissue layer, the epicardium.