A Dynamic Epicardial Injury Response Supports Progenitor Cell Activity during Zebrafish Heart Regeneration

Zebrafish possess a unique yet poorly understood capacity for cardiac regeneration. Here, we show that regeneration proceeds through two coordinated stages following resection of the ventricular apex. First a blastema is formed, comprised of progenitor cells that express precardiac markers, undergo...

Full description

Saved in:
Bibliographic Details
Published inCell Vol. 127; no. 3; pp. 607 - 619
Main Authors Lepilina, Alexandra, Coon, Ashley N., Kikuchi, Kazu, Holdway, Jennifer E., Roberts, Richard W., Burns, C. Geoffrey, Poss, Kenneth D.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 03.11.2006
Subjects
Animals
Animals, Genetically Modified
Animals, Outbred Strains
Cell Differentiation
Heart - physiology
Heart Injuries - pathology
Heart Injuries - physiopathology
Heart Ventricles - pathology
Heart Ventricles - physiopathology
Heart Ventricles - surgery
Male
Models, Cardiovascular
Myocardium - metabolism
Myocardium - pathology
Pericardium - injuries
Regeneration - genetics
Regeneration - physiology
Stem Cells - physiology
Zebrafish - genetics
Zebrafish - physiology
Online AccessGet full text

Cover

More Information
Summary:Zebrafish possess a unique yet poorly understood capacity for cardiac regeneration. Here, we show that regeneration proceeds through two coordinated stages following resection of the ventricular apex. First a blastema is formed, comprised of progenitor cells that express precardiac markers, undergo differentiation, and proliferate. Second, epicardial tissue surrounding both cardiac chambers induces developmental markers and rapidly expands, creating a new epithelial cover for the exposed myocardium. A subpopulation of these epicardial cells undergoes epithelial-to-mesenchymal transition (EMT), invades the wound, and provides new vasculature to regenerating muscle. During regeneration, the ligand fgf17b is induced in myocardium, while receptors fgfr2 and fgfr4 are induced in adjacent epicardial-derived cells. When fibroblast growth factors (Fgf) signaling is experimentally blocked by expression of a dominant-negative Fgf receptor, epicardial EMT and coronary neovascularization fail, prematurely arresting regeneration. Our findings reveal injury responses by myocardial and epicardial tissues that collaborate in an Fgf-dependent manner to achieve cardiac regeneration.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2006.08.052