Cellular and molecular networks governing myelination dynamics in the central nervous system

Myelin, a multilamellar membrane structure enwrapping axons, is essential for rapid saltatory conduction, metabolic support, and long-term axonal integrity in the central nervous system (CNS). Myelination by oligodendrocytes (OLs) constitutes a highly dynamic and orchestrated process, encompassing distinct stages: target axon recognition, axonal wrapping, membrane expansion, and compaction. This review comprehensively summarizes recent advances in understanding the dynamics of CNS myelination which is spatiotemporally regulated through a complex interplay of membrane protein interaction, neuronal activity, metabolic checkpoints, and mechanosensory mechanisms. We highlight how adhesive molecules, cytoskeletal dynamics, and polarized membrane trafficking collectively drive the precise spiraling of myelin around axons. Furthermore, we emphasize the indispensable non-cell autonomous roles of astrocytes and microglia, which contribute critically through lipid transfer, phagocytic refinement, and modulation of the extracellular matrix. Beyond development, we discuss mechanisms that sustain myelin homeostasis, such as autophagy-lysosomal clearance. By integrating these mechanistic insights, we not only underscore the exquisite precision of CNS myelination but also illuminate potential therapeutic targets for demyelinating disorders.