title: A dual epimorphic and compensatory mode of heart regeneration in zebrafish.
abstract: Zebrafish heart regeneration relies on the capacity of cardiomyocytes to proliferate upon injury. To understand the principles of this process after cryoinjury-induced myocardial infarction, we established a spatio-temporal map of mitotic cardiomyocytes and their differentiation dynamics. Immunodetection of phosphohistone H3 and embryonic ventricular heavy chain myosin highlighted two distinct regenerative processes during the early phase of regeneration. The injury-abutting zone comprises a population of cardiac cells that reactivates the expression of embryo-specific sarcomeric proteins and it displays a 10-fold higher mitotic activity in comparison to the injury-remote zone. The undifferentiated cardiomyocytes resemble a blastema-like structure between the original and wound tissues. They integrate with the fibrotic tissue through the fibronectin-tenascin C extracellular matrix, and with the mature cardiomyocytes through upregulation of the tight junction marker, connexin 43. During the advanced regenerative phase, the population of undifferentiated cardiomyocytes disperses within the regenerating myocardium and it is not detected after the termination of regeneration. Although the blastema represents a transient landmark of the regenerating ventricle, the remaining mature myocardium also displays an enhanced mitotic index when compared to uninjured hearts. This suggests an unexpected contribution of a global proliferative activity to restore the impaired cardiac function. Based on these findings, we propose a new model of zebrafish heart regeneration that involves a combination of blastema-dependent epimorphosis and a compensatory organ-wide response.
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Pauline
authors.initials: P
authors.lastname: Sallin
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: de Preux Charles
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duruz
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pfefferli
authors.affiliation: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland. Electronic address: anna.jazwinska@unifr.ch.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaźwińska
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008940:Mitotic Index; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D019063:Tenascin / Q000378:metabolism; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D005353:Fibronectins; D006657:Histones; D019063:Tenascin; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins
keywords: Blastema; Cardiac undifferentiated cells; Cell cycle; Compensatory growth; Embryonic ventricular myosin; Epimorphic regeneration; Heart regeneration; N2.261; Phosphohistone H3; Zebrafish