PUBLICATION

Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart.

Authors
Münch, J., Grivas, D., González-Rajal, Á., Torregrosa-Carrión, R., de la Pompa, J.L.
ID
ZDB-PUB-170301-6
Date
2017
Source
Development (Cambridge, England)   144(8): 1425-1440 (Journal)
Registered Authors
de la Pompa, José Luis
Keywords
Notch, endocardium, heart regeneration, myocardium, serpine1, signalling
Datasets
GEO:GSE68650
MeSH Terms
  • Models, Biological
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
  • Sus scrofa
  • Cell Proliferation
  • Up-Regulation
  • Wound Healing
  • Regeneration*
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Cell Differentiation
  • Homeodomain Proteins/metabolism*
  • Signal Transduction*
  • Endocardium/metabolism*
  • Endocardium/pathology
  • Plasminogen Activator Inhibitor 1/metabolism*
  • Nerve Tissue Proteins/metabolism*
  • Endothelial Cells/metabolism
  • Animals
  • Receptor, Notch1/metabolism*
  • Freezing
(all 23)
PubMed
28242613 Full text @ Development
Abstract
The zebrafish heart regenerates after ventricular damage through a process involving inflammation, fibrotic tissue deposition/removal and myocardial regeneration. Using 3D whole-mount imaging, we reveal a highly dynamic endocardium during cardiac regeneration, including changes in cell morphology, behaviour and gene expression. These events lay the foundation for an initial expansion of the endocardium that matures to form a coherent endocardial structure within the injury site. We studied two important endocardial molecules, Serpine1 and Notch, which are implicated in different aspects of endocardial regeneration. Notch signalling regulates developmental gene expression and features of endocardial maturation. Also, Notch manipulation interferes with attenuation of the inflammatory response and cardiomyocyte proliferation and dedifferentiation. serpine1 is strongly expressed very early in the wound endocardium, with decreasing expression at later time points. serpine1 expression persists in Notch-abrogated hearts, via what appears to be a conserved mechanism. Functional inhibition studies show that Serpine1 controls endocardial maturation and proliferation and cardiomyocyte proliferation. Thus, we describe a highly dynamic endocardium in the regenerating zebrafish heart, with two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.
Genes / Markers
Figures
Figure Gallery (17 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment by injection: RO4929097Protruding-mouth
WTchemical treatment by injection: RO4929097Protruding-mouth
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
WTcryoablation: cardiac ventricleAdult
1 - 10 of 43
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kca3TgTransgenic Insertion
    kca4TgTransgenic Insertion
      md3TgTransgenic Insertion
        sqet33mi60AEtTransgenic Insertion
          sqet331AEtTransgenic Insertion
            y1TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              Fish
              kca3Tg; kca4Tg
              WT
              1 - 2 of 2
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              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GAL4EFGGAL4
              mRFPEFGmRFP
              1 - 3 of 3
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              Mapping
              No data available
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              Citation
              Münch, J., Grivas, D., González-Rajal, Á., Torregrosa-Carrión, R., de la Pompa, J.L. (2017) Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart.. Development (Cambridge, England). 144(8):1425-1440.