PUBLICATION

Heart Regeneration in the Mexican Cavefish

Authors
Stockdale, W.T., Lemieux, M.E., Killen, A.C., Zhao, J., Hu, Z., Riepsaame, J., Hamilton, N., Kudoh, T., Riley, P.R., van Aerle, R., Yamamoto, Y., Mommersteeg, M.T.M.
ID
ZDB-PUB-181127-42
Date
2018
Source
Cell Reports   25: 1997-2007.e7 (Journal)
Registered Authors
Kudoh, Tetsuhiro, Yamamoto, Yoshiyuki
Keywords
Mexican cavefish, QTL, fibrotic scar, heart regeneration, lrrc10, myocardial proliferation
MeSH Terms
  • Kinetics
  • Quantitative Trait Loci/genetics
  • Myocytes, Cardiac/cytology
  • Up-Regulation
  • Animals
  • Myocardium/cytology
  • Cell Proliferation
  • Regeneration/physiology*
  • Wound Healing
  • Heart/physiology*
  • Mutation/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish/physiology
  • Characidae/genetics
  • Characidae/physiology*
(all 15)
PubMed
30462998 Full text @ Cell Rep.
Abstract
Although Astyanax mexicanus surface fish regenerate their hearts after injury, their Pachón cave-dwelling counterparts cannot and, instead, form a permanent fibrotic scar, similar to the human heart. Myocardial proliferation peaks at similar levels in both surface fish and Pachón 1 week after injury. However, in Pachón, this peak coincides with a strong scarring and immune response, and ultimately, cavefish cardiomyocytes fail to replace the scar. We identified lrrc10 to be upregulated in surface fish compared with Pachón after injury. Similar to cavefish, knockout of lrrc10 in zebrafish impairs heart regeneration without affecting wound cardiomyocyte proliferation. Furthermore, using quantitative trait locus (QTL) analysis, we have linked the degree of heart regeneration to three loci in the genome, identifying candidate genes fundamental to the difference between scarring and regeneration. Our study provides evidence that successful heart regeneration entails a delicate interplay between cardiomyocyte proliferation and scarring.
Genes / Markers
Figures
Figure Gallery (3 images)
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Expression
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Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf3011
    Small Deletion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    lrrc10CRISPR1-lrrc10CRISPR
    lrrc10CRISPR2-lrrc10CRISPR
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    Fish
    1 - 2 of 2
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    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available