A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lepilina, A; Coon, AN; Kikuchi, K; Holdway, JE; Roberts, RW; Burns, CG; Poss, KD

Published Date

  • November 3, 2006

Published In

Volume / Issue

  • 127 / 3

Start / End Page

  • 607 - 619

PubMed ID

  • 17081981

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2006.08.052


  • eng

Conference Location

  • United States