Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Lei Li
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States
Kai Zhao
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
Lei Bai
Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Ailian Wang
Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Xiaoqiu Shu
Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Yatao Xiao
Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Jianmin Zhang
Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Kejing Zhang
Department of Neurology, the First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Zhejiang, China
Tiankun Hui
Institute of Life Science, Nanchang University, Nanchang, Jiangxi, China
Wenbing Chen
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States; Institute of Life Science, Nanchang University, Nanchang, Jiangxi, China
Bin Zhang
Department of Physiology, School of Basic Medicine, Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, China
Wei Hsu
Department of Biomedical Genetics, Center for Oral Biology, James Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, United States
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, United States
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.
