PUBLICATION

Endothelin signalling mediates experience-dependent myelination in the CNS

Authors
Swire, M., Kotelevtsev, Y., Webb, D.J., Lyons, D.A., Ffrench-Constant, C.
ID
ZDB-PUB-191030-1
Date
2019
Source
eLIFE   8: (Journal)
Registered Authors
Lyons, David A.
Keywords
mouse, neuroscience, rat, zebrafish
MeSH Terms
  • Myelin Sheath/metabolism*
  • Zebrafish
  • Prefrontal Cortex/physiology
  • Animals
  • Oligodendroglia/metabolism*
  • Signal Transduction*
  • Endothelins/metabolism*
  • Protein Kinase C-epsilon/metabolism*
  • Mice
  • Receptor, Endothelin B/metabolism*
(all 10)
PubMed
31657718 Full text @ Elife
Abstract
Experience and changes in neuronal activity can alter CNS myelination, but the signalling pathways responsible remain poorly understood. Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myelin sheaths formed by individual oligodendrocytes in mouse and zebrafish. We show that this phenotype is also observed in the prefrontal cortex of mice following social isolation, and is associated with reduced expression of vascular endothelin. Additionally, we show that increasing endothelin signalling rescues this myelination defect caused by social isolation. Together, these results indicate that the vasculature responds to changes in neuronal activity associated with experience by regulating endothelin levels, which in turn affect the myelinating capacity of oligodendrocytes. This pathway may be employed to couple the metabolic support function of myelin to activity-dependent demand and also represents a novel mechanism for adaptive myelination.
Genes / Markers
Figures
Figure Gallery (17 images) / 2
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Expression
No data available
Phenotype
Fish Conditions Stage Phenotype Figure
ednrbatlf802/tlf802controlDay 4
ednrbatlf802/tlf802controlDay 4
ednrbatlf802/tlf802controlDay 4
ednrbatlf802/tlf802chemical treatment by environment: protein kinase C agonistDay 4
ednrbatlf802/tlf802; ue1TgcontrolDay 4
ednrbatlf802/tlf802; ue1TgcontrolDay 4
1 - 6 of 6
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
tlf802
    		Point Mutation
    ue1TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
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      Fish
      Fish
      ednrbatlf802/tlf802
      ednrbatlf802/tlf802; ue1Tg
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      Orthology
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      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
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      Citation
      Swire, M., Kotelevtsev, Y., Webb, D.J., Lyons, D.A., Ffrench-Constant, C. (2019) Endothelin signalling mediates experience-dependent myelination in the CNS. eLIFE. 8:.