Fractalkine-Dependent Microglial Pruning of Viable Oligodendrocyte Progenitor Cells Regulates Myelination

• Published in: Cell reports (Cambridge) Vol. 32; no. 7; p. 108047
• Main Authors: Nemes-Baran, Ashley D., White, Donovan R., DeSilva, Tara M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-08-2020
• Subjects: engulfment; fractalkine receptor; microglia; myelin; oligodendrocyte; oligodendrocyte progenitor cell; phagocytosis; phagoptosis; pruning; white matter development; engulfment; myelin; phagocytosis; pruning; white matter development; oligodendrocyte; phagoptosis; microglia; fractalkine receptor; oligodendrocyte progenitor cell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108047

Oligodendrogenesis occurs during early postnatal development, coincident with neurogenesis and synaptogenesis, raising the possibility that microglia-dependent pruning mechanisms that modulate neurons regulate myelin sheath formation. Here we show a population of ameboid microglia migrating from the ventricular zone into the corpus callosum during early postnatal development, termed “the fountain of microglia,” phagocytosing viable oligodendrocyte progenitor cells (OPCs) before onset of myelination. Fractalkine receptor-deficient mice exhibit a reduction in microglial engulfment of viable OPCs, increased numbers of oligodendrocytes, and reduced myelin thickness but no change in axon number. These data provide evidence that microglia phagocytose OPCs as a homeostatic mechanism for proper myelination. A hallmark of hypomyelinating developmental disorders such as periventricular leukomalacia and of adult demyelinating diseases such as multiple sclerosis is increased numbers of oligodendrocytes but failure to myelinate, suggesting that microglial pruning of OPCs may be impaired in pathological states and hinder myelination.
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•Ameboid microglia invade the corpus callosum and engulf OPCs during development•Majority of OPCs engulfed by ameboid microglia in the corpus callosum are viable•Fractalkine receptor-deficient microglia exhibit a reduction in engulfment of OPCs•Fractalkinereceptor-deficient mice have reduced myelin thickness in adulthood
Nemes-Baran et al. show that ameboid microglia engulf living oligodendrocyte progenitor cells (OPCs) during brain development. Fractalkine receptor-deficient microglia exhibit a reduction in engulfment of OPCs, resulting in a surplus of oligodendrocytes and impaired myelination. These data provide evidence that microglia phagocytose OPCs as a homeostatic mechanism required for normal myelination.