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 manip...

Full description

Bibliographic Details
Main Authors: Jenea M. Bin, Daumante Suminaite, Silvia K. Benito-Kwiecinski, Linde Kegel, Maria Rubio-Brotons, Jason J. Early, Daniel Soong, Matthew R. Livesey, Richard J. Poole, David A. Lyons
Format: Article
Language:English
Published: Nature Portfolio 2024-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-45908-6
_version_ 1827326770773229568
author Jenea M. Bin
Daumante Suminaite
Silvia K. Benito-Kwiecinski
Linde Kegel
Maria Rubio-Brotons
Jason J. Early
Daniel Soong
Matthew R. Livesey
Richard J. Poole
David A. Lyons
author_facet Jenea M. Bin
Daumante Suminaite
Silvia K. Benito-Kwiecinski
Linde Kegel
Maria Rubio-Brotons
Jason J. Early
Daniel Soong
Matthew R. Livesey
Richard J. Poole
David A. Lyons
author_sort Jenea M. Bin
collection DOAJ
description 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.
first_indexed 2024-03-07T14:50:19Z
format Article
id doaj.art-2b19a064e0d044c39dccbbb7e1cd2aee
institution Directory Open Access Journal
issn 2041-1723
language English
last_indexed 2024-03-07T14:50:19Z
publishDate 2024-02-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj.art-2b19a064e0d044c39dccbbb7e1cd2aee2024-03-05T19:43:14ZengNature PortfolioNature Communications2041-17232024-02-0115111910.1038/s41467-024-45908-6Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axonsJenea M. Bin0Daumante Suminaite1Silvia K. Benito-Kwiecinski2Linde Kegel3Maria Rubio-Brotons4Jason J. Early5Daniel Soong6Matthew R. Livesey7Richard J. Poole8David A. Lyons9Centre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghCentre for Discovery Brain Sciences, University of EdinburghDepartment of Cell and Developmental Biology, University College LondonCentre for Discovery Brain Sciences, University of EdinburghAbstract 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.https://doi.org/10.1038/s41467-024-45908-6
spellingShingle Jenea M. Bin
Daumante Suminaite
Silvia K. Benito-Kwiecinski
Linde Kegel
Maria Rubio-Brotons
Jason J. Early
Daniel Soong
Matthew R. Livesey
Richard J. Poole
David A. Lyons
Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
Nature Communications
title Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
title_full Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
title_fullStr Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
title_full_unstemmed Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
title_short Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons
title_sort importin 13 dependent axon diameter growth regulates conduction speeds along myelinated cns axons
url https://doi.org/10.1038/s41467-024-45908-6
work_keys_str_mv AT jeneambin importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT daumantesuminaite importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT silviakbenitokwiecinski importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT lindekegel importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT mariarubiobrotons importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT jasonjearly importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT danielsoong importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT matthewrlivesey importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT richardjpoole importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons
AT davidalyons importin13dependentaxondiametergrowthregulatesconductionspeedsalongmyelinatedcnsaxons