Neuronal remodeling and myelination are two fundamental processes during neurodevelopment. How they influence each other remains largely unknown, even though their coordinated execution is critical for circuit function and often disrupted in neuropsychiatric disorders. It is unclear whether myelination stabilizes axon branches during remodeling or whether ongoing remodeling delays myelination. By modulating synaptic transmission, cytoskeletal dynamics, and axonal transport in mouse motor axons, we show that local axon remodeling delays myelination onset and node formation. Conversely, glial differentiation does not determine the outcome of axon remodeling. Delayed myelination is not due to a limited supply of structural components of the axon-glial unit but rather is triggered by increased transport of signaling factors that initiate myelination, such as neuregulin. Further, transport of promyelinating signals is regulated via local cytoskeletal maturation related to activity-dependent competition. Our study reveals an axon branch-specific fine-tuning mechanism that locally coordinates axon remodeling and myelination.

中文翻译：

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神经元重塑的完成促使髓鞘沿运动轴突分支发育。

神经元重塑和髓鞘化是神经发育过程中的两个基本过程。尽管它们的协调执行对于回路功能至关重要，并且经常在神经精神疾病中被破坏，但它们如何相互影响仍然很大程度上未知。不清楚髓鞘形成是否在重塑过程中稳定轴突分支，或者正在进行的重塑是否延迟髓鞘形成。通过在小鼠运动轴突中调节突触传递，细胞骨架动力学和轴突运输，我们表明局部轴突重塑延迟了髓鞘形成和结节的形成。相反，神经胶质分化并不能决定轴突重塑的结果。延迟的髓鞘形成不是由于轴突-神经胶质单元结构成分的供应有限，而是由引发髓鞘形成的信号转导因子的运输增加所触发，如神经调节蛋白。此外，通过与活动依赖性竞争有关的局部细胞骨架成熟来调节早幼粒信号的运输。我们的研究揭示了特定于轴突分支的微调机制，可局部协调轴突的重塑和髓鞘形成。