Oligodendrocytes

Abstract

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 (, 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. (, 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..

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 βIV‐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 (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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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]