Oligodendrocyte precursor cells ingest axons in the mouse neocortex

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Developing brains refine neuronal circuits through structural changes.
• Glial cells, like microglia and astrocytes, are known to prune axons and synapses.
• The precise roles of different glial cells in this process are not fully understood due to technical challenges.

Purpose of the Study:

• To investigate the contribution of various glial cell types to axon pruning during brain development.
• To precisely define the 3D morphology and phagocytic activity of glial cells in the developing mouse visual cortex.

Main Methods:

• Large-scale serial section transmission electron microscopy (TEM) was employed.
• Computational volume segmentation was used to reconstruct glial cell morphologies.
• Single-nucleus RNA sequencing was performed on developing mouse cortical cells.

Main Results:

• Oligodendrocyte precursor cells (OPCs) were found to frequently surround and engulf axonal branches.
• Phagosomes and phagolysosomes (PLs) were abundant in OPC processes, indicating active phagocytosis.
• OPCs expressed phagocytic and neuronal genes, supporting their role in axon pruning.
• PLs were ten times more abundant in OPCs than in microglia, suggesting a major role for OPCs.

Conclusions:

• OPCs are significant contributors to axon pruning and neuronal circuit refinement during cortical development.
• This challenges the prevailing view that microglia are the primary agents of this process.
• OPCs actively participate in shaping neural circuits through phagocytosis.