Abstract
ABSTRACTThe 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.
Highlights
The epicardium is the outer mesothelial layer of the heart
Constriction of the dorsal pericardium leads to apical extrusion of proepicardial cells To investigate PE formation, we analyzed the movement of mesothelial cells in the pericardium of zebrafish embryos
Most PE cells appear as clusters in the dorsal pericardium (DP) proximal to the venous pole (VP) and the atrio-ventricular canal (AVC) of the heart tube (Fig. 1A)
Summary
The epicardium is the outer mesothelial layer of the heart. The epicardium sustains the underlying myocardium through paracrine signals that promote its growth A.E., 0000-0002-9979-8002; M.G.-C., 0000-0003-2455-6671; D.B., 0000-00025758-8402; J.L.d.I.P., 0000-0001-6761-7265; J.V., 0000-0002-8924-732X; N.M., 0000-0002-0905-6399 2010; Pérez-Pomares and de la Pompa, 2011). It is an important cell source during embryogenesis. Epicardiumderived cells (EPDCs) differentiate into cardiac fibroblasts and other cell types (Chau et al, 2014). Upon cardiac injury in zebrafish, EPDCs promote tissue repair and regeneration (Kennedy-Lydon and Rosenthal, 2015; Simoes and Riley, 2018)
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