Motoneuron Wnts regulate neuromuscular junction development

eLife

Bin Zhang¹  Wen-Cheng Xiong²  Xiaoqiu Shu³  Jianmin Zhang³  Lei Bai³  Yatao Xiao³  Chengyong Shen³  Ailian Wang³  Kejing Zhang³  Kai Zhao⁴  Lei Li⁵  Wenbing Chen⁵  Lin Mei⁵  Wei Hsu⁶  Tiankun Hui⁷ 

[1] Institute of Life Science, Nanchang University, Nanchang, Jiangxi, China;Department of Biomedical Genetics, Center for Oral Biology, James Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States;Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China;Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia, United States;Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States;Department of Physiology, School of Basic Medicine, Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China;Institute of Life Science, Nanchang University, Nanchang, Jiangxi, China;

关键词: neuromuscular junction;    synapse;    Wnt;    presynapse;   

DOI  :  10.7554/eLife.34625

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown