The Brain’s Unexpected Pruning Service: OPCs Join the Cleanup Crew

For decades, neuroscientists have viewed oligodendrocyte progenitor cells (OPCs) somewhat reductively—essentially as apprentices waiting to become the brain’s insulators. However, new findings suggest these cells possess a far more voracious appetite than previously imagined. Research utilising human multi-lineage forebrain organoids has demonstrated that OPCs actively participate in synaptic remodelling, effectively 'eating' excess connections during early development.

The study highlights a sophisticated biochemical handshake involving the TAM receptor axis. Through single-nucleus transcriptomic profiling, researchers identified that neurons and microglia release a protein called GAS6. This protein binds specifically to AXL receptors located on a subset of OPCs. This GAS6-AXL signalling triggers the OPCs to engulf and internalise synaptic material. Crucially, when researchers chemically inhibited these receptors or targeted the reduction of AXL expression, the synaptic uptake was significantly impaired.

This discovery paints a complex picture of the developing human brain, where multiple cell types collaborate to refine neural circuitry. While microglia have long held the title of the brain’s primary immune scavengers, it appears they share the gardening duties with their oligodendrocyte cousins. Unravelling this mechanism offers fresh insight into how our neural networks are sculpted and may provide vital clues regarding neurodevelopmental disorders where synaptic pruning goes awry.