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.
Completion of neuronal remodeling prompts myelination along developing motor axon branches
T. Kleele’s present address is École Polytechnique Fédérale de Lausanne, SB IPHYS LEB BSP 428 (Cubotron UNIL), Lausanne, Switzerland.
G. Plucinska’s present address is Guus Vleugelplantsoen 26, Utrecht, Netherlands.
M.H. Schwab’s present address is Department of Neuropathology, University Hospital Leipzig, Leipzig, Germany.
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Mengzhe Wang, Tatjana Kleele, Yan Xiao, Gabriela Plucinska, Petros Avramopoulos, Stefan Engelhardt, Markus H. Schwab, Matthias Kneussel, Tim Czopka, Diane L. Sherman, Peter J. Brophy, Thomas Misgeld, Monika S. Brill; Completion of neuronal remodeling prompts myelination along developing motor axon branches. J Cell Biol 5 April 2021; 220 (4): e201911114. doi: https://doi.org/10.1083/jcb.201911114
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