Abstract
Oligodendrocytes (OLs) generate myelin membranes for the rapid propagation of electrical signals along axons in the central nervous system (CNS) and provide metabolites to support axonal integrity and function. Differentiation of OLs from oligodendrocyte progenitor cells (OPCs) is orchestrated by a multitude of intrinsic and extrinsic factors in the CNS. Disruption of this process, or OL loss in the developing or adult brain, as observed in various neurological conditions including hypoxia/ischemia, stroke, and demyelination, results in axonal dystrophy, neuronal dysfunction, and severe neurological impairments. While much is known regarding the intrinsic regulatory signals required for OL lineage cell progression in development, studies from pathological conditions highlight the importance of the CNS environment and external signals in regulating OL genesis and maturation. Here, we review the recent findings in OL biology in the context of the CNS physiological and pathological conditions, focusing on extrinsic factors that facilitate OL development and regeneration.
Highlights
The central nervous system (CNS) integrates and processes an immense amount of information leading to complex behavior
Recent advances in OL biology have provided mechanistic insights into how OLs develop and regenerate in response to extrinsic signals
Heterogeneity in the oligodendrocyte progenitor cells (OPCs) and OL populations adds another layer of complexity to the intricate, finely tuned regulation of myelination, which may have profound impacts on our brain function
Summary
The central nervous system (CNS) integrates and processes an immense amount of information leading to complex behavior This multilevel process requires an extensive network of neural cell types to be established and maintained. One of the most important regulators of OL lineage cell development is oligodendrocyte transcription factor 2 (Olig2), which acts as a central node upon which numerous pathways converge and from which foundational intrinsic signals arise to drive OPC genesis and maturation [3, 4, 6,7,8]. We will discuss the role of extrinsic factors in regulating the progression of OL lineage cells from immature, migrating precursors to fully differentiated, myelinating oligodendrocytes in development, aging, and disease (Fig. 1)
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