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 - 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 - Uribe, Veronica A1 - Ramadass, Radhan A1 - Dogra, Deepika A1 - Rasouli, S. Javad A1 - Gunawan, Felix A1 - Nakajima, Hiroyuki A1 - Chiba, Ayano A1 - Reischauer, Sven A1 - Mochizuki, Naoki A1 - Stainier, Didier Y. R. T1 - In vivo analysis of cardiomyocyte proliferation during trabeculation JF - Development : Company of Biologists N2 - Cardiomyocyte proliferation is crucial for cardiac growth, patterning and regeneration; however, few studies have investigated the behavior of dividing cardiomyocytes in vivo. Here, we use time-lapse imaging of beating hearts in combination with the FUCCI system to monitor the behavior of proliferating cardiomyocytes in developing zebrafish. Confirming in vitro observations, sarcomere disassembly, as well as changes in cell shape and volume, precede cardiomyocyte cytokinesis. Notably, cardiomyocytes in zebrafish embryos and young larvae mostly divide parallel to the myocardial wall in both the compact and trabecular layers, and cardiomyocyte proliferation is more frequent in the trabecular layer. While analyzing known regulators of cardiomyocyte proliferation, we observed that the Nrg/ErbB2 and TGF beta signaling pathways differentially affect compact and trabecular layer cardiomyocytes, indicating that distinct mechanisms drive proliferation in these two layers. In summary, our data indicate that, in zebrafish, cardiomyocyte proliferation is essential for trabecular growth, but not initiation, and set the stage to further investigate the cellular and molecular mechanisms driving cardiomyocyte proliferation in vivo. KW - Heart development KW - Cardiomyocyte proliferation KW - Trabeculation KW - Sarcomere Y1 - 2018 U6 - https://doi.org/10.1242/dev.164194 SN - 0950-1991 SN - 1477-9129 VL - 145 IS - 14 PB - Company biologists LTD CY - Cambridge ER -