KLC4 shapes axon arbors during development and mediates adult behavior
- University of Wisconsin-Madison, United States
- National Innovation Center for Advanced Medical Devices, China
- Morgridge Institute for Research, United States
Abstract
Development of elaborate and polarized neuronal morphology requires precisely regulated transport of cellular cargos by motor proteins such as kinesin-1. Kinesin-1 has numerous cellular cargos which must be delivered to unique neuronal compartments. The process by which this motor selectively transports and delivers cargo to regulate neuronal morphogenesis is poorly understood, although the cargo-binding kinesin light chain (KLC) subunits contribute to specificity. Our work implicates one such subunit, KLC4, as an essential regulator of axon branching and arborization pattern of sensory neurons during development. Using live imaging approaches in klc4 mutant zebrafish, we show that KLC4 is required for stabilization of nascent axon branches, proper microtubule (MT) dynamics, and endosomal transport. Furthermore, KLC4 is required for proper tiling of peripheral axon arbors: in klc4 mutants, peripheral axons showed abnormal fasciculation, a behavior characteristic of central axons. This result suggests that KLC4 patterns axonal compartments and helps establish molecular differences between central and peripheral axons. Finally, we find that klc4 mutant larva are hypersensitive to touch and adults show anxiety-like behavior in a novel tank test, implicating klc4 as a new gene involved in stress response circuits.
Data availability
All data generated or analyzed in this study are included in the manuscript and supporting files. Source Data files have been provided for Figures 1-12.
Article and author information
Author details
Funding
National Institutes of Health (R01 NS086934)
- Mary C Halloran
National Institutes of Health (R21 NS116326)
- Mary C Halloran
National Institutes of Health (F32 NS098689)
- Elizabeth M Haynes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Fabienne E. Poulain, University of South Carolina, United States
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animals were handled according to approved institutional animal care and use committee protocols of the University of Wisconsin (protocols L005692 and L005704).
Version history
- Preprint posted: September 26, 2021 (view preprint)
- Received: September 28, 2021
- Accepted: October 11, 2022
- Accepted Manuscript published: October 12, 2022 (version 1)
- Version of Record published: October 25, 2022 (version 2)
Copyright
© 2022, Haynes et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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KLC4 shapes axon arbors during development and mediates adult behavior
eLife 11:e74270.
https://doi.org/10.7554/eLife.74270
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