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Development. 2019 Jul 4;146(13). pii: dev174961. doi: 10.1242/dev.174961.

Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells.

Author information

1
Development of the Epicardium and its Role During Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
2
Department of Anatomy, Histology and Neuroscience, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
3
Institute of Anatomy, University of Bern, 3000 Bern 9, Switzerland.
4
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.
5
Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France.
6
Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France.
7
Université de Strasbourg, 67411 Illkirch, France.
8
Intercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
9
Ciber CV, 28029 Madrid, Spain.
10
Hubrecht Institute-KNAW and UMC Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
11
Development 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.

Abstract

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.

KEYWORDS:

Actomyosin; Bmp; Cell extrusion; Heart development; Proepicardium; Zebrafish

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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