Motoneuron Wnts regulate neuromuscular junction development
- Zhejiang University, China
- Case Western Reserve University, United States
- Augusta University, United States
- Nanchang University, China
- Huazhong University of Science and Technologyy, China
- University of Rochester Medical Center, United States
Abstract
The neuromuscular junction (NMJ) is a synapse between motoneurons and skeletal muscles to control motor behavior. Unlike extensively investigated postsynaptic differentiation, less is known about mechanisms of presynaptic assembly. Genetic evidence of Wnt in mammalian NMJ development was missing due to the existence of multiple Wnts and their receptors. We show when Wnt secretion is abolished from motoneurons by mutating the Wnt ligand secretion mediator (Wls) gene, mutant mice showed muscle weakness and neurotransmission impairment. NMJs were unstable with reduced synaptic junctional folds and fragmented AChR clusters. Nerve terminals were swollen; synaptic vesicles were fewer and mislocated. The presynaptic deficits occurred earlier than postsynaptic deficits. Intriguingly, these phenotypes were not observed when deleting Wls in muscles or Schwann cells. We identified Wnt7A and Wnt7B as major Wnts for nerve terminal development in rescue experiments. These observations demonstrate a necessary role of motoneuron Wnts in NMJ development, in particular presynaptic differentiation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National key research and development program of china (2017YFA0104903)
- Chengyong Shen
Zhejiang provincial Natural Sciences Foundation of China (LR17H090001)
- Chengyong Shen
National Natural Science Foundation of China (31671040)
- Chengyong Shen
National Natural Science Foundation of China (31701036)
- Kejing Zhang
National Institutes of Health
- Lin Mei
National Institutes of Health
- Wen-Cheng Xiong
Muscular Dystrophy Association
- Lin Mei
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeremy Nathans, Johns Hopkins University School of Medicine, United States
Ethics
Animal experimentation: Experiments with animals were approved by Institutional Animal Care andUse Committees of Augusta University (2011-0393), Case Western Reserve University (2017-0115), and Zhejiang University (10262).
Version history
- Received: December 27, 2017
- Accepted: August 9, 2018
- Accepted Manuscript published: August 16, 2018 (version 1)
- Version of Record published: September 7, 2018 (version 2)
Copyright
© 2018, Shen 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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Motoneuron Wnts regulate neuromuscular junction development
eLife 7:e34625.
https://doi.org/10.7554/eLife.34625
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