Figure 1.

Synapse elimination promotes myelination of terminal motor axon branches. During early development, NMJs are innervated by multiple axons that compete for endplate territory. During this time, the terminal branches of the axons are not myelinated, and the tubulin cytoskeletal network remains immature. Synaptic activity induces elimination of redundant connections, which leads the winner axon’s microtubule-based cytoskeleton to mature and increase, while the microtubule cytoskeleton is degraded in the retracting axon. The maturity of the cytoskeleton allows for kinesin dependent anterograde transport of Neuregulin 1-III, which then initiates a promyelination signaling cascade via AKT and ERK activation.