PUBLICATION

Epicardial Tcf21 facilitates cardiomyocyte dedifferentiation and heart regeneration in zebrafish

Authors
Kalvaitytė-Repečkė, M., Gabrilavičiūtė, S., Kvederavičiūtė, K., Burg, L., Bakūnaitė, E., Poss, K.D., Balciunas, D.
ID
ZDB-PUB-251209-10
Date
2025
Source
Developmental Biology : (Journal)
Registered Authors
Bakūnaitė, Edita, Balciunas, Darius, Poss, Kenneth D.
Keywords
Tcf21, cardiomyocyte dedifferentiation, conditional allele, epicardium, heart regeneration
Datasets
GEO:GSE289891
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Proteins*/genetics
  • Basic Helix-Loop-Helix Proteins*/metabolism
  • Cell Dedifferentiation*/physiology
  • Heart*/physiology
  • Myocytes, Cardiac*/cytology
  • Myocytes, Cardiac*/metabolism
  • Myocytes, Cardiac*/physiology
  • Pericardium*/metabolism
  • Regeneration*/genetics
  • Regeneration*/physiology
  • Tamoxifen/analogs & derivatives
  • Tamoxifen/pharmacology
  • Zebrafish*/genetics
  • Zebrafish*/physiology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
41360282 Full text @ Dev. Biol.
Abstract
Unlike mammals, zebrafish (Danio rerio) are able to regenerate their hearts after injury, making them an excellent model organism for studying the molecular mechanisms underlying heart regeneration. Epicardium, the outermost layer of the heart, is an essential player in this process. Injury-induced epicardium activation, characterized by the expression of embryonic epicardial marker genes including tcf21, supports cardiac regeneration by providing various cell types and releasing paracrine signals that promote the restoration of damaged tissue. However, the molecular mechanisms involved in this process are insufficiently understood. In this study, we describe a conditional tcf21flox allele and use it to investigate the role of Tcf21 in heart regeneration. By employing 4-hydroxytamoxifen inducible CreERT2 recombinase, we eliminated tcf21 expression in adult fish. Our findings indicate that loss of this transcription factor reduces the presence of dedifferentiated cardiomyocytes in the injury area and impairs heart regeneration. This work provides new insights into the molecular basis of the epicardial response to heart injury and its role in guiding heart regeneration.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping