Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells.
Andrés-Delgado LDevelopment of the Epicardium and its Role During Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Ernst AInstitute of Anatomy, University of Bern, 3000 Bern 9, Switzerland.
Galardi-Castilla MDevelopment of the Epicardium and its Role During Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Bazaga DDevelopment of the Epicardium and its Role During Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Peralta MInstitut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.
Münch JIntercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
González-Rosa JMDevelopment of the Epicardium and its Role During Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Marques IInstitute of Anatomy, University of Bern, 3000 Bern 9, Switzerland.
Tessadori FHubrecht Institute-KNAW and UMC Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
de la Pompa JLIntercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Vermot JInstitut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.
Mercader NDevelopment of the Epicardium and its Role During Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain nadia.mercader@ana.unibe.ch.
English
The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis, the epicardium 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 a 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 enables 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 their developmental fate to form a new tissue layer, the epicardium.