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Review
. 2021 May 11:9:661486.
doi: 10.3389/fcell.2021.661486. eCollection 2021.

Glial Cells Promote Myelin Formation and Elimination

Alexandria N Hughes  1
Affiliations
Review

Glial Cells Promote Myelin Formation and Elimination

Alexandria N Hughes. Front Cell Dev Biol. .

Abstract

Building a functional nervous system requires the coordinated actions of many glial cells. In the vertebrate central nervous system (CNS), oligodendrocytes myelinate neuronal axons to increase conduction velocity and provide trophic support. Myelination can be modified by local signaling at the axon-myelin interface, potentially adapting sheaths to support the metabolic needs and physiology of individual neurons. However, neurons and oligodendrocytes are not wholly responsible for crafting the myelination patterns seen in vivo. Other cell types of the CNS, including microglia and astrocytes, modify myelination. In this review, I cover the contributions of non-neuronal, non-oligodendroglial cells to the formation, maintenance, and pruning of myelin sheaths. I address ways that these cell types interact with the oligodendrocyte lineage throughout development to modify myelination. Additionally, I discuss mechanisms by which these cells may indirectly tune myelination by regulating neuronal activity. Understanding how glial-glial interactions regulate myelination is essential for understanding how the brain functions as a whole and for developing strategies to repair myelin in disease.

Keywords: astrocyte; glial-glial interactions; microglia; myelin; oligodendrocyte.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Stages of oligodendrocyte development supported by other glial cells. Oligodendrocyte precursor cells proliferate and migrate, but what determines precise migratory routes and proliferation rate? How do oligodendrocytes differentiate and turn on myelin gene expression? Circulating lipids are a major component of myelin, but where do those lipids come from? Finally, how do myelin sheaths grow, shrink, and disappear altogether?
FIGURE 2
FIGURE 2
Glial cells promote myelin formation and elimination. Oligodendrocyte precursor cell proliferation is promoted by astrocytic PDGF and FGF signaling and OPCs migrate along the vasculature. Endothelin secreted by endothelial cells and IGF1 secreted by microglia promote differentiation, and astrocytes guide OPCs to axons. The generation of myelin membrane (which may be thought of as one feature of differentiation) utilizes lipids and cholesterol produced by astrocytes, BDNF secreted by neurons and potentially augmented by microglia-secreted BDNF, and endothelin signaling to the receptor EDNRB located on oligodendrocytes. Astrocytic secretion of PN-1 promotes myelin stability by inhibiting thrombin-mediated paranodal lifting, whereas microglia phagocytose myelin by detecting phosphatidylserine.
FIGURE 3
FIGURE 3
Glial secreted factors that influence oligodendrocyte development. Oligodendrocyte proliferation, differentiation, myelination, and myelin remodeling are shaped by cues secreted by glial cells. Colored dots indicate cell types that secrete each factor and line type denotes direction of effect. References for each factor are listed in Table 1.
FIGURE 4
FIGURE 4
Astrocytes and microglia regulate and are regulated by neuronal activity: what are the consequences for activity-dependent myelination? (A) Summary schematic of interactions between astrocytes, microglia, neurons, and myelination described by Ishibashi et al. (2006), Badimon et al. (2020), Ma et al. (2016), and Hughes and Appel (2020). (B) Does glial regulation of neuronal activity change activity-dependent myelination? Does microglial suppression of activity (blue neurons) and astrocytic release of ATP to excite nearby neurons (purple) contribute to activity-dependent myelination?
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