PUBLICATION

Myelination of Neuronal Cell Bodies when Myelin Supply Exceeds Axonal Demand

Authors
Almeida, R.G., Pan, S., Cole, K.L.H., Williamson, J.M., Early, J.J., Czopka, T., Klingseisen, A., Chan, J.R., Lyons, D.A.
ID
ZDB-PUB-180410-1
Date
2018
Source
Current biology : CB   28(8): 1296-1305.e5 (Journal)
Registered Authors
Almeida, Rafael, Cole, Katy, Czopka, Tim, Lyons, David A., Williamson, Jill
Keywords
CNS, axon, myelin, myelin mistargeting, myelination, neuron, oligodendrocyte, zebrafish
MeSH Terms
  • Nerve Fibers, Myelinated/metabolism
  • Nerve Fibers, Myelinated/physiology*
  • Zebrafish Proteins/metabolism
  • Organogenesis/physiology
  • Cell Body/metabolism*
  • Mice
  • Zebrafish/metabolism
  • Zebrafish/physiology
  • Female
  • Animals, Genetically Modified
  • Neurons/physiology
  • Male
  • Animals
  • Oligodendroglia/metabolism
  • Axons/metabolism
  • Axons/physiology
  • Myelin Sheath/metabolism*
  • Myelin Sheath/physiology
(all 18)
PubMed
29628374 Full text @ Curr. Biol.
Abstract
The correct targeting of myelin is essential for nervous system formation and function. Oligodendrocytes in the CNS myelinate some axons, but not others, and do not myelinate structures including cell bodies and dendrites [1]. Recent studies indicate that extrinsic signals, such as neuronal activity [2, 3] and cell adhesion molecules [4], can bias myelination toward some axons and away from cell bodies and dendrites, indicating that, in vivo, neuronal and axonal cues regulate myelin targeting. In vitro, however, oligodendrocytes have an intrinsic propensity to myelinate [5-7] and can promiscuously wrap inert synthetic structures resembling neuronal processes [8, 9] or cell bodies [4]. A current therapeutic goal for the treatment of demyelinating diseases is to greatly promote oligodendrogenesis [10-13]; thus, it is important to test how accurately extrinsic signals regulate the oligodendrocyte's intrinsic program of myelination in vivo. Here, we test the hypothesis that neurons regulate myelination with sufficient stringency to always ensure correct targeting. Surprisingly, however, we find that myelin targeting in vivo is not very stringent and that mistargeting occurs readily when oligodendrocyte and myelin supply exceed axonal demand. We find that myelin is mistargeted to neuronal cell bodies in zebrafish mutants with fewer axons and independently in drug-treated zebrafish with increased oligodendrogenesis. Additionally, by increasing myelin production of oligodendrocytes in zebrafish and mice, we find that excess myelin is also inappropriately targeted to cell bodies. Our results suggest that balancing oligodendrocyte-intrinsic programs of myelin supply with axonal demand is essential for correct myelin targeting in vivo and highlight potential liabilities of strongly promoting oligodendrogenesis.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
st23
    Point Mutation
    ue1TgTransgenic Insertion
      ue2TgTransgenic Insertion
        ue3TgTransgenic Insertion
          ue8TgTransgenic Insertion
            vu12TgTransgenic Insertion
              vu234TgTransgenic Insertion
                zf148TgTransgenic Insertion
                  zf234TgTransgenic Insertion
                    zf2162TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      notch1aMO5-notch1aMRPHLNO
                      1 - 1 of 1
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                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-rbfox3monoclonal
                        IgG1Mouse
                        Ab2-map2polyclonal
                          Chicken
                          Ab3-mbpmonoclonal
                            IgG2aRat
                            1 - 3 of 3
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                            Orthology
                            No data available
                            Engineered Foreign Genes
                            Marker Marker Type Name
                            DsRedEFGDsRed
                            EGFPEFGEGFP
                            GAL4EFGGAL4
                            mCherryEFGmCherry
                            mRFPEFGmRFP
                            RFPEFGRFP
                            TagRFPTEFGTagRFPT
                            1 - 7 of 7
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                            Mapping
                            No data available