Motoneuron Wnts regulate neuromuscular junction development
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...
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eLife Sciences Publications Ltd
2018-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/34625 |
| _version_ | 1811235928796037120 |
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| author | Chengyong Shen Lei Li Kai Zhao Lei Bai Ailian Wang Xiaoqiu Shu Yatao Xiao Jianmin Zhang Kejing Zhang Tiankun Hui Wenbing Chen Bin Zhang Wei Hsu Wen-Cheng Xiong Lin Mei |
| author_facet | Chengyong Shen Lei Li Kai Zhao Lei Bai Ailian Wang Xiaoqiu Shu Yatao Xiao Jianmin Zhang Kejing Zhang Tiankun Hui Wenbing Chen Bin Zhang Wei Hsu Wen-Cheng Xiong Lin Mei |
| author_sort | Chengyong Shen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:00:38Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:00:38Z |
| publishDate | 2018-08-01 |
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| spelling | doaj.art-ab3bd57e151843409aab0203f27d58022022-12-22T03:33:52ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.34625Motoneuron Wnts regulate neuromuscular junction developmentChengyong Shen0https://orcid.org/0000-0001-8184-8190Lei Li1Kai Zhao2Lei Bai3Ailian Wang4Xiaoqiu Shu5Yatao Xiao6Jianmin Zhang7Kejing Zhang8Tiankun Hui9Wenbing Chen10Bin Zhang11Wei Hsu12Wen-Cheng Xiong13https://orcid.org/0000-0001-9071-7598Lin Mei14https://orcid.org/0000-0001-5772-1229Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaDepartment of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United StatesDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia, United StatesDepartment of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaDepartment of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaDepartment of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaDepartment of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaDepartment of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaDepartment of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, ChinaInstitute of Life Science, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States; Institute of Life Science, Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Physiology, School of Basic Medicine, Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Biomedical Genetics, Center for Oral Biology, James Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United StatesDepartment of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, United StatesDepartment of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, United StatesThe 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.https://elifesciences.org/articles/34625neuromuscular junctionsynapseWntpresynapse |
| spellingShingle | Chengyong Shen Lei Li Kai Zhao Lei Bai Ailian Wang Xiaoqiu Shu Yatao Xiao Jianmin Zhang Kejing Zhang Tiankun Hui Wenbing Chen Bin Zhang Wei Hsu Wen-Cheng Xiong Lin Mei Motoneuron Wnts regulate neuromuscular junction development eLife neuromuscular junction synapse Wnt presynapse |
| title | Motoneuron Wnts regulate neuromuscular junction development |
| title_full | Motoneuron Wnts regulate neuromuscular junction development |
| title_fullStr | Motoneuron Wnts regulate neuromuscular junction development |
| title_full_unstemmed | Motoneuron Wnts regulate neuromuscular junction development |
| title_short | Motoneuron Wnts regulate neuromuscular junction development |
| title_sort | motoneuron wnts regulate neuromuscular junction development |
| topic | neuromuscular junction synapse Wnt presynapse |
| url | https://elifesciences.org/articles/34625 |
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