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Fractalkine-Dependent Microglial Pruning of Viable Oligodendrocyte Progenitor Cells Regulates Myelination
Ashley D Nemes-Baran1, Donovan R White1, Tara M DeSilva1
1Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Abstract:
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.
Insights
Microglia prune viable oligodendrocyte progenitor cells (OPCs) during early development to ensure proper myelination. Impaired microglial pruning may contribute to hypomyelinating and demyelinating disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Oligodendrogenesis, the formation of myelin-producing oligodendrocytes, occurs during early postnatal development.
- Microglia, the brain's immune cells, are known to prune neuronal structures.
- The role of microglia in regulating oligodendrocyte progenitor cells (OPCs) and myelination is not fully understood.
Purpose of the Study:
- To investigate the role of microglia in oligodendrocyte progenitor cell (OPC) dynamics during postnatal development.
- To determine if microglia-mediated pruning of OPCs is essential for proper myelin sheath formation.
Main Methods:
- Observation of microglial migration patterns in the corpus callosum during early postnatal development.
- Analysis of oligodendrocyte progenitor cell (OPC) phagocytosis by microglia.
- Utilizing fractalkine receptor-deficient mice to assess the impact on myelination and oligodendrocyte numbers.
Main Results:
- A population of ameboid microglia, termed "the fountain of microglia," was identified migrating and phagocytosing viable OPCs before myelination onset.
- Fractalkine receptor deficiency led to reduced microglial engulfment of OPCs, increased oligodendrocyte numbers, and decreased myelin thickness.
- Axon numbers remained unchanged in fractalkine receptor-deficient mice.
Conclusions:
- Microglia actively phagocytose viable OPCs as a homeostatic mechanism crucial for regulating proper myelination.
- Impaired microglial pruning of OPCs may underlie hypomyelinating disorders (e.g., periventricular leukomalacia) and demyelinating diseases (e.g., multiple sclerosis).
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