PUBLICATION

Tp53 Suppression Promotes Cardiomyocyte Proliferation during Zebrafish Heart Regeneration

Authors
Shoffner, A., Cigliola, V., Lee, N., Ou, J., Poss, K.D.
ID
ZDB-PUB-200904-11
Date
2020
Source
Cell Reports   32: 108089 (Journal)
Registered Authors
Cigliola, Valentina, Ou, Jianhong, Poss, Kenneth D., Shoffner, Adam
Keywords
Mdm2, Tp53, cardiomyocyte, heart regeneration, mitogen, zebrafish
Datasets
GEO:GSE146859
MeSH Terms
  • Animals
  • Cell Proliferation/physiology
  • Genes, p53
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Regeneration/physiology*
  • Tumor Suppressor Protein p53/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics*
PubMed
32877671 Full text @ Cell Rep.
Abstract
Zebrafish regenerate heart muscle through division of pre-existing cardiomyocytes. To discover underlying regulation, we assess transcriptome datasets for dynamic gene networks during heart regeneration and identify suppression of genes associated with the transcription factor Tp53. Cardiac damage leads to fluctuation of Tp53 protein levels, concomitant with induced expression of its central negative regulator, mdm2, in regenerating cardiomyocytes. Zebrafish lacking functional Tp53 display increased indicators of cardiomyocyte proliferation during regeneration, whereas transgenic Mdm2 blockade inhibits injury-induced cardiomyocyte proliferation. Induced myocardial overexpression of the mitogenic factors Nrg1 or Vegfaa in the absence of injury also upregulates mdm2 and suppresses Tp53 levels, and tp53 mutations augment the mitogenic effects of Nrg1. mdm2 induction is spatiotemporally associated with markers of de-differentiation in injury and growth contexts, suggesting a broad role in cardiogenesis. Our findings reveal myocardial Tp53 suppression by mitogen-induced Mdm2 as a regulatory component of innate cardiac regeneration.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes