Wnt/β-catenin signaling acts cell-autonomously to promote cardiomyocyte regeneration in the zebrafish heart

Zebrafish can achieve scar-free healing of heart injuries, and robustly replace all cardiomyocytes lost to injury via dedifferentiation and proliferation of mature cardiomyocytes. Previous studies suggested that Wnt/beta-catenin signaling is active in the injured zebrafish heart, where it induces fibrosis and prevents cardiomyocyte cell cycling. Here, via targeting the destruction complex of the Wnt/beta-catenin pathway with pharmacological and genetic tools, we demonstrate that Wnt/beta-catenin activity is required for cardiomyocyte proliferation and dedifferentiation, as well as for maturation of the scar during regeneration. Using cardiomyocyte-specific conditional inhibition of the pathway, we show that Wnt/beta-catenin signaling acts cell-autonomously to promote cardiomyocyte proliferation. Our results stand in contrast to previous reports and rather support a model in which Wnt/beta-catenin signaling plays a positive role during heart regeneration in zebrafish.

Automated summary

The Wnt/β-catenin signaling pathway is shown to play a positive role in heart regeneration in zebrafish, promoting cardiomyocyte proliferation, dedifferentiation, and scar maturation. Contrary to previous reports, this new study supports the importance of Wnt/β-catenin signaling in the regeneration process.