Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons

Abstract

Axon diameter influences the conduction properties of myelinated axons, both directly, and indirectly through effects on myelin. However, we have limited understanding of mechanisms controlling axon diameter growth in the central nervous system, preventing systematic dissection of how manipulating diameter affects myelination and conduction along individual axons. Here we establish zebrafish to study axon diameter. We find that importin 13b is required for axon diameter growth, but does not affect cell body size or axon length. Using neuron-specific ipo13b mutants, we assess how reduced axon diameter affects myelination and conduction, and find no changes to myelin thickness, precision of action potential propagation, or ability to sustain high frequency firing. However, increases in conduction speed that occur along single myelinated axons with development are tightly linked to their growth in diameter. This suggests that axon diameter growth is a major driver of increases in conduction speeds along myelinated axons over time.

Metadata

Item Type:	Article
Authors/Creators:	Bin, J.M. Suminaite, D. Benito-Kwiecinski, S.K. Kegel, L. Rubio-Brotons, M. Early, J.J. Soong, D. Livesey, M.R. https://orcid.org/0000-0002-3441-7977 Poole, R.J. Lyons, D.A.
Copyright, Publisher and Additional Information:	© 2024 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.
Keywords:	Development of the nervous system; Myelin biology and repair; Super-resolution microscopy
Dates:	Published: 27 February 2024 Published (online): 27 February 2024 Accepted: 6 February 2024 Submitted: 1 June 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Depositing User:	Symplectic Sheffield
Date Deposited:	13 Feb 2024 12:30
Last Modified:	11 Mar 2024 12:13
Status:	Published
Publisher:	Nature Portfolio
Refereed:	Yes
Identification Number:	10.1038/s41467-024-45908-6
Related URLs:	Software or Code Software or Code
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:208855

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Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons

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