The geometric and spatial constraints of the microenvironment induce oligodendrocyte differentiation.

The oligodendrocyte precursor cell (OPC) arises from the subventricular zone (SVZ) during early vertebrate development to migrate and proliferate along axon tracts before differentiating into the myelin-forming oligodendrocyte. We demonstrate that the spatial and temporal regulation of oligodendrocyte differentiation depends intimately on the axonal microenvironment and the density of precursor cells along a specified axonal area. Differentiation does not require dynamic axonal signaling, but instead is induced by packing constraints resulting from intercellular interactions. Schwann cells and even artificial beads bound to the axonal surface can mimic these constraints and promote differentiation. Together, these results describe the coordinately controlled biophysical interaction of oligodendrocyte precursors within an axonal niche leading to self-renewal and differentiation.