ZFIN ID: ZDB-PUB-170301-6
Notch signalling restricts inflammation and serpine1 in the dynamic endocardium of the regenerating zebrafish heart
Münch, J., Grivas, D., González-Rajal, Á., Torregrosa-Carrión, R., de la Pompa, J.L.
Date: 2017
Source: Development (Cambridge, England) 144(8): 1425-1440 (Journal)
Registered Authors:
Keywords: Notch, endocardium, heart regeneration, myocardium, serpine1, signalling
Microarrays: GEO:GSE68650
MeSH Terms:
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Endocardium/metabolism*
  • Endocardium/pathology
  • Endothelial Cells/metabolism
  • Freezing
  • Homeodomain Proteins/metabolism*
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Models, Biological
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Nerve Tissue Proteins/metabolism*
  • Plasminogen Activator Inhibitor 1/metabolism*
  • Receptor, Notch1/metabolism*
  • Regeneration*
  • Signal Transduction*
  • Sus scrofa
  • Up-Regulation
  • Wound Healing
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed: 28242613 Full text @ Development
FIGURES
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 the 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, in 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 heart and two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.
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