PUBLICATION

Notch regulates blastema proliferation and prevents differentiation during adult zebrafish fin regeneration

Authors
Münch, J., González-Rajal, A., and de la Pompa, J.L.
ID
ZDB-PUB-130201-6
Date
2013
Source
Development (Cambridge, England)   140(7): 1402-1411 (Journal)
Registered Authors
de la Pompa, José Luis
Keywords
none
MeSH Terms
  • Adult Stem Cells/metabolism
  • Adult Stem Cells/physiology
  • Age Factors
  • Animal Fins/embryology
  • Animal Fins/metabolism
  • Animal Fins/physiology*
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/genetics*
  • Cell Proliferation*
  • Down-Regulation/genetics
  • Embryo, Nonmammalian
  • Epithelial Cells/metabolism
  • Epithelial Cells/physiology
  • Gene Expression Regulation, Developmental
  • Models, Biological
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Receptors, Notch/physiology*
  • Regeneration/genetics*
  • Regeneration/physiology
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/physiology
PubMed
23344707 Full text @ Development
Abstract

Zebrafish have the capacity to regenerate several organs, including the heart and fins. Fin regeneration is epimorphic, involving the formation at the amputation plane of a mass of undifferentiated, proliferating mesenchymal progenitor-like cells, called blastema. This tissue provides all the cell types that form the fin, so that after damage or amputation the fin pattern and structure are fully restored. How blastema cells remain in this progenitor-like state is poorly understood. Here, we show that the Notch pathway plays an essential role during fin regeneration. Notch signalling is activated during blastema formation and remains active throughout the regeneration process. Chemical inhibition or morpholino-mediated knockdown of Notch signalling impairs fin regeneration via decreased proliferation accompanied by reduced expression of Notch target genes in the blastema. Conversely, overexpression of a constitutively active form of the Notch1 receptor (N1ICD) in the regenerating fin leads to increased proliferation and to the expansion of the blastema cell markers msxe and msxb, as well as increased expression of the proliferation regulator aldh1a2. This blastema expansion prevents regenerative fin outgrowth, as indicated by the reduction in differentiating osteoblasts and the inhibition of bone regeneration. We conclude that Notch signalling maintains blastema cells in a plastic, undifferentiated and proliferative state, an essential requirement for fin regeneration.

Genes / Markers
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Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes