Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes

Bin, J. M.; Emberley, K.; Buscham, T. J.; Eichel-Vogel, M. A.; Doan, R. A.; Steyer, A. M.; Nolan, M. F.; Möbius, W.; Monk, K. R.; Werner, H. B.; Emery, B.; Lyons, D. A.

doi:10.1101/2025.01.10.632348

bioRxiv · 10.1101/2025.01.10.632348

Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes

Bin, J. M.·Emberley, K.·Buscham, T. J.·Eichel-Vogel, M. A.·Doan, R. A.·Steyer, A. M.·Nolan, M. F.·Möbius, W.·Monk, K. R.·Werner, H. B.·Emery, B.·Lyons, D. A.

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Abstract

Myelination facilitates the rapid conduction of action potentials along axons. In the central nervous system (CNS), myelinated axons vary over 100-fold in diameter, with conduction speed scaling linearly with increasing diameter. Axon diameter and myelination are closely interlinked, with axon diameter exerting a strong influence on myelination. Conversely, myelinating Schwann cells in the peripheral nervous system can both positively and negatively affect axon diameter. However, whether axon diameter is regulated by CNS oligodendrocytes is less clear. Here, we investigated CNS axon diameter growth in the absence of myelin using mouse (Mbpshi/shi and Myrf conditional knockout) and zebrafish (olig2 morpholino) models. We find that neither the ensheathment of axons, nor the formation of compact myelin are required for CNS axons to achieve appropriate and diverse diameters. This indicates that developmental CNS axon diameter growth is independent of myelination, and shows that myelinating cells of CNS and PNS differentially influence axonal morphology.

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Bin, J. M., Emberley, K., Buscham, T. J., Eichel-Vogel, M. A., Doan, R. A., Steyer, A. M., Nolan, M. F., Möbius, W., Monk, K. R., Werner, H. B., Emery, B., Lyons, D. A.. 2025-01-10. Developmental axon diameter growth of central nervous system axons does not depend on ensheathment or myelination by oligodendrocytes. https://doi.org/10.1101/2025.01.10.632348

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