PUBLICATION

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

Authors
Bertozzi, A., Wu, C.C., Hans, S., Brand, M., Weidinger, G.
ID
ZDB-PUB-211109-22
Date
2021
Source
Developmental Biology   481: 226-237 (Journal)
Registered Authors
Brand, Michael, Hans, Stefan, Weidinger, Gilbert, Wu, Chi-Chung
Keywords
Axin1, Cardiomyocyte, Cryoinjury, Fibrosis, Heart, Proliferation, Regeneration, Scar, Wnt signaling, Wnt/β-catenin, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation
  • Myocardium/metabolism*
  • Myocytes, Cardiac/metabolism*
  • Regeneration*
  • Wnt Signaling Pathway*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • beta Catenin/genetics
  • beta Catenin/metabolism*
PubMed
34748730 Full text @ Dev. Biol.
Abstract
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/β-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/β-catenin pathway with pharmacological and genetic tools, we demonstrate that Wnt/β-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/β-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/β-catenin signaling plays a positive role during heart regeneration in zebrafish.
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