He has been at CNIC since 2009. His research interest focuses on cardiac valves development and disease. -Juliane Münch is a postdoctoral researcher at Potsdam University and the BSRT at Charité, Berlin, Germany. She made her PhD at CNIC in Madrid, Spain, studying the role of Notch signalling in zebrafish fin and heart regeneration. Her current research focuses on the specification of endocardial progenitors during early zebrafish development. -José Luis de la Pompa is senior investigator at CNIC. He made his PhD in Drosophila developmental genetics at CSIC (Spain), postdoctoral in chicken development (EMBL, Germany) and mouse developmental genetics (Ontario Cancer Institute, Canada). CSIC investigator since 2003 and CNIC full professor and senior investigator since 2009. His research centers in the role of cell signalling in cardiac development and disease, and the genetics of CHD.
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.
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