Heart Regeneration in Zebrafish

TLDR

In mammals and amphibians, cardiac injury usually causes scarring and little heart muscle regeneration. Regeneration is driven by vigorous cardiomyocyte proliferation at the epicardial edge of the new myocardium. Zebrafish hearts regenerate completely within two months after 20% ventricular resection, whereas Mps1 mutants fail to regenerate and scar, showing that cardiomyocyte proliferation can overcome scarring and positioning zebrafish as a valuable model for studying cardiac regeneration.

Abstract

Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Thus, injury-induced cardiomyocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. These findings indicate that zebrafish will be useful for genetically dissecting the molecular mechanisms of cardiac regeneration.