title: Notch signalling restricts inflammation andserpine1expression in the dynamic endocardium of the regenerating zebrafish heart.
abstract: 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.serpine1is strongly expressed very early in the wound endocardium, with decreasing expression at later time points.serpine1expression 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.
authors.affiliation: Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid E-28029, Spain.|Institute of Biochemistry and Biology, Potsdam University, Karl-Liebknecht-Straße 24-25, Potsdam D-14476, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Münch
authors.affiliation: Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid E-28029, Spain.|CIBER CV, 28029 Madrid, Spain.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Grivas
authors.affiliation: Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid E-28029, Spain.|Cancer Division, Garvan Institute of Medical Research, The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst NSW 2010, Australia.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: González-Rajal
authors.affiliation: Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid E-28029, Spain.|CIBER CV, 28029 Madrid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Torregrosa-Carrión
authors.affiliation: Intercellular Signalling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro 3, Madrid E-28029, Spain jlpompa@cnic.es.|CIBER CV, 28029 Madrid, Spain.
authors.forename: José Luis
authors.identifier: 0000-0001-6761-7265
authors.initials: JL
authors.lastname: de la Pompa
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D005615:Freezing; D018398:Homeodomain Proteins / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D034421:Sus scrofa; D015854:Up-Regulation; D014945:Wound Healing; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D017395:Plasminogen Activator Inhibitor 1; D051881:Receptor, Notch1; C000609826:SERPINe1 protein, zebrafish; D029961:Zebrafish Proteins; C437805:notch1a protein, zebrafish
keywords: Endocardium; Heart regeneration; Myocardium; Notch; Serpine1; Signalling