Selective Cortical Myelination Reflects Axon-Driven Progression of the BCAS1-positive Oligodendrocyte Lineage

Myelination in the cerebral cortex is sparse, discontinuous, showing marked heterogeneity across cortical areas and along individual axons, yet the mechanisms that establish this complex and selective architecture remain unclear. Using histological mapping of oligodendrocyte lineage cells across cortical areas combined with longitudinal in vivo imaging, we find that initial myelination is highly targeted: up to 80 percent of the earliest segments arise consecutively along the same subset of axons. We observed that oligodendrocyte precursor cells enter a premyelinating BCAS1-positive state even within cortical regions that remain poorly myelinated or unmyelinated. However, the progression beyond early premyelinating morphologies correlates with local myelin levels and with interactions with specific neuronal partners. BCAS1-positive ensheathments show a preferential stabilisation and elongation along parvalbumin interneurons compared with somatostatin interneurons, linking regional neuronal composition to differential myelin levels. These findings indicate that cortical myelination emerges from intrinsic lineage programs that are refined through selective interactions with axons, thereby linking neuronal diversity to cortical myelin distribution and providing a framework to understand why remyelination may fail in regions where myelination supportive neuronal populations are reduced.