TY  - JOUR
A1  - Andrés-Delgado, Laura
A1  - Ernst, Alexander
A1  - Galardi-Castilla, María
A1  - Bazaga, David
A1  - Peralta, Marina
A1  - Münch, Juliane
A1  - Gonzalez-Rosa, Juan M.
A1  - Marques, Inês
A1  - Tessadori, Federico
A1  - de la Pompa, José Luis
A1  - Vermot, Julien
A1  - Mercader, Nadia
T1  - Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells
JF  - Development : Company of Biologists
N2  - 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.
KW  - Actomyosin
KW  - Bmp
KW  - Cell extrusion
KW  - Proepicardium
KW  - Zebrafish
KW  - Heart development
Y1  - 2019
U6  - https://doi.org/10.1242/dev.174961
SN  - 0950-1991
SN  - 1477-9129
VL  - 146
IS  - 13
PB  - The Company of Biologists Ltd
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Muench, Juliane
A1  - Grivas, Dimitrios
A1  - Gonzalez-Rajal, Alvaro
A1  - Torregrosa-Carrion, Rebeca
A1  - de la Pompa, José Luis
T1  - Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart
JF  - Development : Company of Biologists
N2  - The zebrafish heart regenerates after ventricular damage through a process involving inflammation, fibrotic tissue deposition/removal and myocardial regeneration. Using 3D whole-mount imaging, we reveal a highly dynamic endocardium during cardiac regeneration, including changes in cell morphology, behaviour and gene expression. These events lay the foundation for an initial expansion of the endocardium that matures to form a coherent endocardial structure within the injury site. We studied two important endocardial molecules, Serpine1 and Notch, which are implicated in different aspects of endocardial regeneration. Notch signalling regulates developmental gene expression and features of endocardial maturation. Also, Notch manipulation interferes with attenuation of the inflammatory response and cardiomyocyte proliferation and dedifferentiation. serpine1 is strongly expressed very early in the wound endocardium, with decreasing expression at later time points. serpine1 expression persists in Notch-abrogated hearts, via what appears to be a conserved mechanism. Functional inhibition studies show that Serpine1 controls endocardial maturation and proliferation and cardiomyocyte proliferation. Thus, we describe a highly dynamic endocardium in the regenerating zebrafish heart, with two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.
KW  - Heart regeneration
KW  - Endocardium
KW  - Myocardium
KW  - Signalling
KW  - Serpine1
KW  - Notch
Y1  - 2017
U6  - https://doi.org/10.1242/dev.143362
SN  - 0950-1991
SN  - 1477-9129
VL  - 144
SP  - 1425
EP  - 1440
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -