Oligodendrocytes

Sara Szuchet, The University of Chicago, Chicago, Illinois, USA
Miriam S Domowicz, The University of Chicago, Chicago, Illinois, USA
Lynn D Hudson, National Institute of Health, Bethesda, Maryland, USA

Published online: November 2010

DOI: 10.1002/9780470015902.a0000289.pub2

Oligodendrocytes – a type of central nervous system glial cell – have diverse origins and are morphologically and phenotypically heterogeneous. They present two phenotypes: myelinating and nonmyelinating that derive from a common precursor pool. In the spinal cord, oligodendrocyte precursors and motor neurons arise from the same niche. In the embryonic forebrain, ganglionic eminences harbour sites that generate GABAergic neurons and oligodendrocyte precursors destined to populate the telencephalon. A strict spatio-temporal expression of transcription factors and signalling molecules ensures the orderly appearance of precursors, their migration and differentiation. The two oligodendrocyte phenotypes are functionally interlocked with neurons. Myelinating oligodendrocytes associate with axons and organise them into segments surrounded by the multilayer membrane, myelin, separated by bare regions – nodes of Ranvier – that express voltage-gated sodium channels, players in the generation of action potentials. Myelin contributes to axonal architecture. Nonmyelinating oligodendrocytes adhere to neuronal somata, but their code of communication is still unknown. In multiple sclerosis myelin is destroyed, oligodendrocytes die and axons degenerate. This overall knowledge constitutes a scaffold upon which further advancements are built.

Key Concepts:

  • Oligodendrocytes – one of the neural cell types from the central nervous system that have diverse origins and are morphologically and phenotypically hetererogeneous.
  • Oligodendrocytes provide support to axons that is independent of their role in the assembly and maintenance of myelin.
  • Oligodendrocytes are vulnerable cells because the making and sustaining of myelin come at a great metabolic cost.
  • Myelin is an intricate membrane organelle unique to vertebrate organisms.
  • Myelin is a multilayer membrane not only essential for fast nerve conduction, but is also a critical determinant of axonal architecture.
  • The advent of myelin marked an evolutionary leap because it allowed for the development of large organisms, but their existence is irrevocably tied to it.
  • The interaction between an oligodendrocyte and an axon is one of the most complex cell-to-cell communications.
  • Transcription factors act in a cell context–specific mode and regulate the determination of cellular fate.
  • Genetic and epigenetic factors exert strict supervision on nervous system development.
  • Diseases of oligodendrocytes or myelin can be classified as demyelinating or dysmyelinating.

Keywords: myelin; glial cells; oligodendrocyte–neuron interaction; transcription factors; signalling pathways; cell fate specification; remyelination; multiple sclerosis; oligodendrocyte nonmyelinating phenotype; neural stem cells

Figure 1. Interactions that regulate the switch from generating motor neurons to producing oligodendrocytes. Reproduced from Rowitch (2004, Figure 5), with permission from Nature Publishing Group. During embryogenesis, the tight regulation of sonic hedgehog (Shh) and delta/jagged-notch signalling in conjunction with transcription factors Nkx6, Ngn2 and Sox9 ensures the timely switch from the generation of motor neurons to that of oligodendrocyte precursors. At this point, the pro-oligodendrocyte transcription factors, Sox10 and Nkx2.2, enter the field to carry the cells to a myelinating phenotype. It is noteworthy that Olig 2 is active throughout.
Figure 2. Schematic of myelinated axons. A single oligodendrocyte is shown with six processes emanating from the cell body. Each process terminates in a single myelin internode that ensheathes part of an axon. The regions between the myelin internodes, in which the ‘bare’ axon is apparent, are the nodes of Ranvier. The oligodendrocyte is ensheathing three different axons, each of which has a different axonal diameter and a different length of internode. The topmost axon has the smallest diameter, and the number of myelin wraps is accordingly reduced. The action potential originates in the cell body of the neuron. The bottom-most axon is shown in cross-section, with an enlargement of the compact myelin. The alternating dark and light electron-dense lines represent the close apposition of the intracellular face (the major dense line) and the extracellular face (the intraperiod line) of the oligodendrocyte plasma membranes. The myelin sheath directly adjacent to the node of Ranvier is not compact; instead, some cytoplasm remains between the membrane layers and forms the ‘paranodal loops’. The sodium channels in the axonal membrane at the node of Ranvier are represented by cylinders, and the potassium channels in the paranodal region are represented by circles. The arrows indicate the influx of sodium that occurs at the nodes of Ranvier when the action potential is propagated along the axon, followed by an efflux of potassium from the potassium channels in the paranodal region.
Figure 3. Axon to oligodendrocyte signalling that controls CNS myelination. Reproduced from Taveggia et al. (2010, Figure 2), with permission from Nature Publishing Group. This figure shows some of the receptors that might be implicated in initiating the signalling pathways that would culminate in myelination. It indicates potential down stream effectors as well as transcription factors in the nucleus that would partake in the transcription of myelin proteins. The dashed line in the nucleus separates factors that act as inhibitors of myelin protein synthesis from those that activate it. For a more detailed account see Taveggia et al. (2010).
Figure 4. Structure of a CNS myelinated axon. Depicted here are the principal components responsible for the organisation of the nodes of Ranvier. We note the presence of sodium channels (Nav 1.6), adhesion molecules Nrcam and neurofascin, ankyrin-G and IV-spectrin. Present on the extracellular side and secreted by glial cells are versican V2, tenascin-R and phosphocan. Astrocytic processes cover this site (not illustrated). Major constituents contributing to the paranodal loops by the axon are contactin and caspr; oligodendrocytes provide neurofascin-155. Most of the potassium channels are located at the juxtaparanodes.
Figure 5. The polyclonal antibody OTMP recognises perineuronal oligodendrocytes in cortical grey matter but does not stain neurons. Rat brain sections were labelled for OTMP (red), NeuN (green), and DAPI (blue) and examined by confocal microscopy. Figure 5(a) shows an oligodendrocyte indenting the neuronal soma (arrow) and its processes enveloping the neuron. In (b) single oligodendrocyte makes contact to several neuronal cell bodies with its processes (arrowheads).
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 References
    Barnett MH, Parratt JDE, Pollard JD et al. (2009) MS: is it one disease? International MS Journal 16: 57–65.
    Bradl M and Lassmann H (2010) Oligodendrocytes: biology and pathology. Acta Neuropatholgica 119: 37–53.
    Brady ST, Witt AS, Kirkpatrick LL et al. (1999) Formation of compact myelin is required for maturation of the axonal cytoskeleton. Journal of Neuroscience 19: 7278–7288.
    Bunge RP (1968) Glial cells and the central myelin sheath. Physical Review 48: 197–251.
    Butt AM and Berry M (2000) Oligodendrocytes and the control of myelination in vivo: new insights from the rat anterior medullary velum. Journal of Neuroscience Research 59: 477–488.
    Cahoy JD, Emery B, Kaushal A et al. (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. Journal of Neuroscience 28: 264–278.
    Cai J, Qi Y, Hu X et al. (2005) Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45: 41–53.
    de Castro F and Bribian A (2005) The molecular orchestra of the migration of oligodendrocyte precursors during development. Brain Research Reviews 49: 227–241.
    Cayre M, Canoll P and Goldman JE (2009) Cell migration in the normal and pathological postnatal mammalian brain. Progress in Neurobiology 88: 41–63.
    Costa MR, Gotz M and Berninger B (2010) What determines neurogenic competence in glia. Brain Research Reviews 9 doi 10.1016/j.brainresrev.2010.01.002.
    Dours-Zimmermann MT, Maurer K, Rauch U et al. (2009) Versican V2 assembles the extracellular matrix surrounding the nodes of ranvier in the CNS. Journal of Neuroscience 29: 7731–7742.
    Dugas JC, Tai YC, Speed TP et al. (2006) Functional genomic analysis of oligodendrocyte differentiation. Journal of Neuroscience 26: 10967–10983.
    Fogarty M, Richardson WD and Kessaris N (2005) A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord. Development 132: 1951–1959.
    Garbern JY (2007) Pelizaeus-Merzbacher disease: genetic and cellular pathogenesis. Cellular Molecular Life Sciences 64: 50–65.
    other Garbern JY and Hobson GM (2010) PLP1-related disorders. Gene Reviews [Internet] Books and Text: 1–27.
    Gorski JA, Talley T, Qiu M et al. (2002) Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. Journal of Neuroscience 22: 6309–6314.
    Hartman BK, Agrawal HC, Agrawal D et al. (1982) Development and maturation of central nervous system myelin: comparison of immunohistochemical localization of proteolipid protein and basic protein in myelin and oligodendrocytes. Proceedings of the National Academy of Sciences of the USA 79: 4217–4220.
    He W, Ingraham C, Rising L et al. (2001) Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis. Journal of Neuroscience 21: 8854–8862.
    Hudson LD, Puckett C, Berndt J et al. (1989) Mutation of the proteolipid protein gene PLP in a human X chromosome-linked myelin disorder. Proceedings of the National Academy of Sciences of the USA 86: 8128–8131.
    Hurst S, Garbern J, Trepanier A et al. (2006) Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease. Genetic Medicine 8: 371–378.
    Kessaris N, Fogarty M, Iannarelli P et al. (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nature Neuroscience 9: 173–179.
    Liu A, Han YR, Li J et al. (2007) The glial or neuronal fate choice of oligodendrocyte progenitors is modulated by their ability to acquire an epigenetic memory. Journal of Neuroscience 27: 7339–7343.
    Liu R, Cai J, Hu X et al. (2003) Region-specific and stage-dependent regulation of Olig gene expression and oligodendrogenesis by Nkx6.1 homeodomain transcription factor. Development 130: 6221–6231.
    Lu QR, Yuk DI, Alberta JA et al. (2000) Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25: 317–329.
    Marshall CA and Goldman JE (2002) Subpallial dlx2-expressing cells give rise to astrocytes and oligodendrocytes in the cerebral cortex and white matter. Journal of Neuroscience 22: 9821–9830.
    Merkle FT and Alvarez-Buylla A (2006) Neural stem cells in mammalian development. Current Opinion in Cell Biology 18: 704–709.
    Miller FD and Gauthier AS (2007) Timing is everything: making neurons versus glia in the developing cortex. Neuron 54: 357–369.
    Nave KA (2010) Myelination and the trophic support of long axons. National Review of Neuroscience 11: 275–283.
    Nave KA and Boespflug-Tanguy O (1996) X-linked developmental defects of myelination: from mouse mutants to human genetic diseases. Neuroscientist 2: 33–43.
    Nave KA and Trapp BD (2008) Axon-glial signaling and the glial support of axon function. Annual Review of Neuroscience 31: 535–561.
    Nielsen JA, Maric D, Lau P et al. (2006) Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling. Journal of Neuroscience 26: 9881–9891.
    Petryniak MA, Potter GB, Rowitch DH et al. (2007) Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 55: 417–433.
    book Polak M, Haymaker W, Johnson JE Jr et al. (1982) "Neuroglia and their reactions". In: Haymaker W and Adams RD (eds) Histology and Histopathology of the Nervous System, pp. 363–480. Springfield, IL: Charles C. Thomas, Publisher.
    Poliak S and Peles E (2003) The local differentiation of myelinated axons at nodes of Ranvier. National Review of Neuroscience 4: 968–980.
    book Raine CS (1997) "Oligodendrocytes and central nervous system myelin". In: Davis RL and Robertson DM (eds) Textbook of Neuropathology, 3rd edn, pp. 137–164. Baltimore: Williams & Wilkins.
    Richardson WD, Kessaris N and Pringle N (2006) Oligodendrocyte wars. National Review of Neuroscience 7: 11–18.
    Río-Hortega P del (1928) Tercera aportación al conocimiento morfológico e interpretación funcional de la oligodendroglía. Memorias de la Real Sociedad Española de Historia Natural 14: 5–122.
    Rowitch DH (2004) Glial specification in the vertebrate neural tube. National Review of Neuroscience 5: 409–419.
    Salzer JL (2003) Polarized domains of myelinated axons. Neuron 40: 297–318.
    Sheikh KA, Sun J, Liu Y et al. (1999) Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proceedings of the National Academy of Sciences of the USA 96: 7532–7537.
    Stoffel W and Bosio A (1997) Myelin glycolipids and their functions. Current Opinion in Neurobiology 7: 654–661.
    Stolt CC, Lommes P, Sock E et al. (2003) The Sox9 transcription factor determines glial fate choice in the developing spinal cord. Genes & Development 17: 1677–1689.
    book Szuchet S (1995) "The morphology and ultrastructure of oligodendrocytes and their functional implications". In: Kettenmann H and Ranson B (eds) Neuroglia, pp. 23–43. New York: Oxford University Press.
    other Szuchet S, Nielsen JA, Lovas G et al. (2010) The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. Neural Development (under review).
    book Szuchet S and Seeger MA (2004) "Oligodendrocyte phenotypical and morphological heterogeneity: a reexamination of old concepts in view of new findings". In: Hertz L (ed.) Advances in Molecular and Cellular Biology, vol 31-I, pp. 53–73. Amsterdam: Elsevier B.V.
    Taveggia C, Feltri ML and Wrabetz L (2010) Signals to promote myelin formation and repair. National Review of Neurology 6: 276–287.
    Trofatter JA, Dlouhy SR, DeMyer W et al. (1989) Pelizaeus-Merzbacher disease: tight linkage to proteolipid protein gene exon variant. Proceedings of the National Academy of Sciences of the USA 86: 9427–9430.
    Vallstedt A, Klos JM and Ericson J (2005) Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45(1): 55–67.
    Ventura RE and Goldman JE (2006) Telencephalic oligodendrocytes battle it out. National Neuroscience 9: 153–154.
    Wegner M (2001) Expression of transcription factors during oligodendroglial development. Microtechnology Research Techniques 52: 746–752.
    Witt A and Brady ST (2000) Unwrapping new layers of complexity in axon/glial relationships. Glia 29: 112–117.
    Woodward KJ (2008) The molecular and cellular defects underlying Pelizaeus-Merzbacher disease. Expert Reviews in Molecular Medicine 10: e14.
    Zerlin M, Milosevic A and Goldman JE (2004) Glial progenitors of the neonatal subventricular zone differentiate asynchronously, leading to spatial dispersion of glial clones and to the persistence of immature glia in the adult mammalian CNS. Developmental Biology 270: 200–213.
    Zhou Q, Wang SL and Anderson DJ (2000) Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 25: 331–343.
 Further Reading
    Butler MA and Bennett TL (2003) In search of a conceptualization of multiple sclerosis: a historical perspective. Neuropsychology Review 13: 93–112.
    Franklin RJM and ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nature Reviews 9: 839–855.
    Liu J and Csaccia P (2010) Epigenetic regulation of oligodendrocyte identity. Trends in Neurosciences 33: 193–201.
    Shen S, Sandoval J, Swiss VA et al. (2008) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nature Neuroscience 11: 1024–1034.
    Smith C (2007) A shifting paradigm: histone deacetylases and transcriptional activation. Bioassays 30: 15–24.
    Stephen PJ, Baranzini SE, Chao Z et al. (2009) Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes & Development 23: 1571–1585.
    Vivekanand P and Rebay I (2006) Intersection of signal transduction pathways and development. Annual Review of Genetics 40: 139–157.

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Article Title: Oligodendrocytes
 
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Szuchet, Sara, Domowicz, Miriam S, and Hudson, Lynn D(Nov 2010) Oligodendrocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000289.pub2]