PUBLICATION

Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism

Authors
Zhao, L., Ben-Yair, R., Burns, C.E., Burns, C.G.
ID
ZDB-PUB-190117-6
Date
2019
Source
Cell Reports   26: 546-554.e5 (Journal)
Registered Authors
Burns (Erter), Caroline, Burns, Geoff, Zhao, Long
Keywords
Notch, Wnt, cardiac repair, cardiomyocyte proliferation, heart regeneration, notum, wif, zebrafish
Datasets
GEO:GSE107228
MeSH Terms
  • Receptors, Notch/metabolism*
  • Heart/physiopathology*
  • Cell Proliferation
  • Wnt Signaling Pathway/genetics*
  • Animals
  • Myocytes, Cardiac/metabolism*
  • Zebrafish
  • Mice
PubMed
30650349 Full text @ Cell Rep.
Citation
Zhao, L., Ben-Yair, R., Burns, C.E., Burns, C.G. (2019) Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism. Cell Reports. 26:546-554.e5.
Abstract
Previous studies demonstrate that the regenerative zebrafish heart responds to injury by upregulating Notch receptors in the endocardium and epicardium. Moreover, global suppression of Notch activity following injury impairs cardiomyocyte proliferation and induces scarring. However, the lineage-specific requirements for Notch signaling and full array of downstream targets remain unidentified. Here, we demonstrate that inhibition of endocardial Notch signaling following ventricular amputation compromises cardiomyocyte proliferation and stimulates fibrosis. RNA sequencing uncovered reduced levels of two transcripts encoding secreted Wnt antagonists, Wif1 and Notum1b, in Notch-suppressed hearts. Like Notch receptors, wif1 and notum1b are induced following injury in the endocardium and epicardium. Small-molecule-mediated activation of Wnt signaling is sufficient to impair cardiomyocyte proliferation and induce scarring. Last, Wnt pathway suppression partially restored cardiomyocyte proliferation in hearts experiencing endocardial Notch inhibition. Taken together, our data demonstrate that Notch signaling supports cardiomyocyte proliferation by dampening myocardial Wnt activity during zebrafish heart regeneration.
Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fb13TgTransgenic Insertion
    fb14TgTransgenic Insertion
      fb24TgTransgenic Insertion
        ia4TgTransgenic Insertion
          s896TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            No data available
            Fish
            No data available
            Antibodies
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            CeruleanEFGCerulean
            CreEFGCre
            EGFPEFGEGFP
            GFPEFGGFP
            mCherryEFGmCherry
            mKate2EFGmKate2
            1 - 6 of 6
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            Mapping
            No data available
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