Prrx1b restricts fibrosis and promotes Nrg1-dependent cardiomyocyte proliferation during zebrafish heart regeneration

Dennis E M de Bakker, Mara Bouwman, Esther Dronkers, Filipa C Simões, Paul R Riley, Marie-José Goumans, Anke M Smits, Jeroen Bakkers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

16 Citations (Scopus)


Fibroblasts are activated to repair the heart following injury. Fibroblast activation in the mammalian heart leads to a permanent fibrotic scar that impairs cardiac function. In other organisms, such as zebrafish, cardiac injury is followed by transient fibrosis and scar-free regeneration. The mechanisms that drive scarring versus scar-free regeneration are not well understood. Here, we show that the homeobox-containing transcription factor Prrx1b is required for scar-free regeneration of the zebrafish heart as the loss of Prrx1b results in excessive fibrosis and impaired cardiomyocyte proliferation. Through lineage tracing and single-cell RNA sequencing, we find that Prrx1b is activated in epicardial-derived cells where it restricts TGFβ ligand expression and collagen production. Furthermore, through combined in vitro experiments in human fetal epicardial-derived cells and in vivo rescue experiments in zebrafish, we conclude that Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte proliferation. Collectively, these results indicate that Prrx1 is a key transcription factor that balances fibrosis and regeneration in the injured zebrafish heart. This article has an associated 'The people behind the papers' interview.

Original languageEnglish
JournalDevelopment (Cambridge)
Issue number19
Publication statusPublished - 01 Oct 2021


  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Collagen/metabolism
  • Fibroblasts/metabolism
  • Fibrosis
  • Heart/physiology
  • Homeodomain Proteins/genetics
  • Humans
  • Myocytes, Cardiac/metabolism
  • Neuregulin-1/metabolism
  • Regeneration
  • Transforming Growth Factor beta/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics


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