PUBLICATION

Human ARF Specifically Inhibits Epimorphic Regeneration in the Zebrafish Heart

Authors
Lee, S., Hesse, R., Tamaki, S., Garland, C., Pomerantz, J.H.
ID
ZDB-PUB-200624-2
Date
2020
Source
Genes   11(6): (Journal)
Registered Authors
Keywords
Alternative Reading Frame (ARF), cardiac regeneration, epimorphic regeneration
MeSH Terms
  • Mice
  • Animals
  • ADP-Ribosylation Factor 1/genetics
  • Regeneration/genetics*
  • Myocytes, Cardiac/metabolism
  • Humans
  • Extremities/growth & development
  • Extremities/physiopathology
  • Cell Proliferation/genetics
  • Myocardial Infarction/genetics
  • Myocardial Infarction/rehabilitation
  • Myocardial Infarction/therapy*
  • Heart/growth & development*
  • Heart/physiopathology
  • Cyclin-Dependent Kinase Inhibitor p16/genetics*
  • Genes, Tumor Suppressor
  • Zebrafish/genetics
  • Zebrafish/growth & development
(all 18)
PubMed
32570883 Full text @ Genes (Basel)
Abstract
The Alternative Reading Frame (ARF) protein is a tumor suppressor encoded by the Cyclin Dependent Kinase Inhibitor 2A gene in mammals but not lower regenerative vertebrates, and has been previously implicated as a context-sensitive suppressor of regeneration in murine skeletal muscle and humanized ARF-expressing zebrafish fins. This study extends our investigation of the role of ARF in the regeneration of other solid tissues, including the zebrafish heart and the mammalian digit. Heart regeneration after cryoinjury was used to mimic massive myocardial infarction. ARF gene expression was upregulated during the cardiac regenerative process and slowed the rate of morphological recovery. ARF specifically impacts cardiomyocytes, neovascularization, and the endothelial-mesenchymal transition, while not affecting epicardial proliferation. This suggests that in the context of regeneration, ARF is specifically expressed in cells undergoing dedifferentiation. To investigate ARF as a suppressor of epimorphic regeneration in mammalian systems, we also tested whether the absence of ARF was permissive for murine digit regeneration, but found that ARF absence alone was insufficient to significantly alter digit restoration. These findings provide additional evidence that ARF suppresses epimorphic regeneration, but suggests that modulation of ARF alone is insufficient to permit regeneration.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf706TgTransgenic Insertion
    zf707TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      Human Disease Fish Conditions Evidence
      myocardial infarctionTAS
      1 - 1 of 1
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      Sequence Targeting Reagents
      No data available
      Fish
      1 - 3 of 3
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      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
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      Mapping
      No data available