PUBLICATION

Regulation of zebrafish heart regeneration by miR-133

Authors
Yin, V.P., Lepilina, A., Smith, A., and Poss, K.D.
ID
ZDB-PUB-120301-26
Date
2012
Source
Developmental Biology   365(2): 319-327 (Journal)
Registered Authors
Lepilina, Alexandra, Poss, Kenneth D.
Keywords
zebrafish, heart, regeneration, microRNAs, miR-133
MeSH Terms
  • Zebrafish/physiology*
  • Heart Injuries/physiopathology
  • Transgenes
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Cell Proliferation
  • Animals
  • Heart/physiology*
  • Myocytes, Cardiac/physiology*
  • Regeneration*
(all 11)
PubMed
22374218 Full text @ Dev. Biol.
Abstract

Zebrafish regenerate cardiac muscle after severe injuries through the activation and proliferation of spared cardiomyocytes. Little is known about factors that control these events. Here we investigated the extent to which miRNAs regulate zebrafish heart regeneration. Microarray analysis identified many miRNAs with increased or reduced levels during regeneration. miR-133, a miRNA with known roles in cardiac development and disease, showed diminished expression during regeneration. Induced transgenic elevation of miR-133 levels after injury inhibited myocardial regeneration, while transgenic miR-133 depletion enhanced cardiomyocyte proliferation. Expression analyses indicated that cell cycle factors mps1, cdc37, and PA2G4, and cell junction components cx43 and cldn5, are miR-133 targets during regeneration. With pharmacological inhibition and EGFP sensor interaction studies, we demonstrated that cx43 is a new miR-133 target and regeneration gene. Our results reveal dynamic regulation of miRNAs during heart regeneration, and indicate that miR-133 restricts injury-induced cardiomyocyte proliferation.

Genes / Markers
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
pd47TgTransgenic Insertion
    pd48TgTransgenic Insertion
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      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
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