TY - JOUR A1 - MacGrogan, Donal A1 - Münch, Juliane A1 - de la Pompa, José Luis T1 - Notch and interacting signalling pathways in cardiac development, disease, and regeneration JF - Nature Reviews Cardiology N2 - Cardiogenesis is a complex developmental process involving multiple overlapping stages of cell fate specification, proliferation, differentiation, and morphogenesis. Precise spatiotemporal coordination between the different cardiogenic processes is ensured by intercellular signalling crosstalk and tissue-tissue interactions. Notch is an intercellular signalling pathway crucial for cell fate decisions during multicellular organismal development and is aptly positioned to coordinate the complex signalling crosstalk required for progressive cell lineage restriction during cardiogenesis. In this Review, we describe the role of Notch signalling and the crosstalk with other signalling pathways during the differentiation and patterning of the different cardiac tissues and in cardiac valve and ventricular chamber development. We examine how perturbation of Notch signalling activity is linked to congenital heart diseases affecting the neonate and adult, and discuss studies that shed light on the role of Notch signalling in heart regeneration and repair after injury. KW - Cardiac regeneration KW - Cell signalling KW - Congenital heart defects KW - Heart development Y1 - 2018 U6 - https://doi.org/10.1038/s41569-018-0100-2 SN - 1759-5002 SN - 1759-5010 VL - 15 IS - 11 SP - 685 EP - 704 PB - Nature Publ. Group CY - New York ER - 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 -