PUBLICATION

The regenerative capacity of the zebrafish heart is dependent on TGFβ signaling

Authors
Chablais, F., and Jazwinska, A.
ID
ZDB-PUB-120423-6
Date
2012
Source
Development (Cambridge, England)   139(11): 1921-1930 (Journal)
Registered Authors
Jazwinska, Anna
Keywords
none
MeSH Terms
  • Dioxoles/pharmacology
  • Immunohistochemistry
  • Tenascin
  • Benzamides/pharmacology
  • Zebrafish/physiology*
  • In Situ Hybridization
  • Animals
  • Smad3 Protein/metabolism
  • Signal Transduction/physiology*
  • Protein Serine-Threonine Kinases/antagonists & inhibitors
  • Protein Serine-Threonine Kinases/metabolism
  • Electrocardiography
  • Receptors, Transforming Growth Factor beta/antagonists & inhibitors
  • Receptors, Transforming Growth Factor beta/metabolism
  • Histological Techniques
  • Regeneration/drug effects
  • Regeneration/physiology*
  • Heart/physiology*
  • Transforming Growth Factor beta/metabolism*
  • Cicatrix/metabolism
  • Myocytes, Cardiac/physiology
(all 21)
PubMed
22513374 Full text @ Development
Abstract

Mammals respond to a myocardial infarction by irreversible scar formation. By contrast, zebrafish are able to resolve the scar and to regenerate functional cardiac muscle. It is not known how opposing cellular responses of fibrosis and new myocardium formation are spatially and temporally coordinated during heart regeneration in zebrafish. Here, we report that the balance between the reparative and regenerative processes is achieved through Smad3-dependent TGFβ signaling. The type I receptor alk5b (tgfbr1b) is expressed in both fibrotic and cardiac cells of the injured heart. TGFβ ligands are locally induced following cryoinjury and activate the signaling pathway both in the infarct area and in cardiomyocytes in the vicinity of the trauma zone. Inhibition of the relevant type I receptors with the specific chemical inhibitor SB431542 qualitatively altered the infarct tissue and completely abolished heart regeneration. We show that transient scar formation is an essential step to maintain robustness of the damaged ventricular wall prior to cardiomyocyte replacement. Taking advantage of the reversible action of the inhibitor, we dissected the multifunctional role of TGFβ signaling into three crucial processes: collagen-rich scar deposition, Tenascin C-associated tissue remodeling at the infarct-myocardium interface, and cardiomyocyte proliferation. Thus, TGFβ signaling orchestrates the beneficial interplay between scar-based repair and cardiomyocyte-based regeneration to achieve complete heart regeneration.

Genes / Markers
Figures
Figure Gallery (16 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f2TgTransgenic Insertion
    pd1TgTransgenic Insertion
      s843TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        1 - 3 of 3
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        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-aldh1a2polyclonalIgGRabbit
        Ab1-mcm5polyclonalRabbit
        Ab1-tgfb1polyclonal
          Rabbit
          Ab1-tncpolyclonal
            IgGRabbit
            Ab1-tpmmonoclonal
              IgG1Mouse
              Ab2-fnpolyclonal
                Rabbit
                Ab2-smad3monoclonal
                  IgGRabbit
                  Ab2-vimmonoclonal
                    IgMMouse
                    1 - 8 of 8
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                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    DsRed2EFGDsRed2
                    EGFPEFGEGFP
                    1 - 2 of 2
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                    Mapping
                    No data available