A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in Caenorhabditis elegans
Jiale Fan,
Tingting Ji,
Kai Wang,
Jichang Huang,
Mengqing Wang,
Laura Manning,
Xiaohua Dong,
Yanjun Shi,
Xumin Zhang,
Zhiyong Shao,
Daniel A Colón-Ramos
Affiliations
Jiale Fan
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Tingting Ji
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Kai Wang
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Jichang Huang
State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China
Mengqing Wang
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Xiaohua Dong
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Yanjun Shi
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China
Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Instituto de Neurobiología, Recinto de Ciencias Médicas, Universidad de Puerto Rico, San Juan, Puerto Rico
Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this process and identified mig-17, a conserved ADAMTS metalloprotease. Proteomic mass spectrometry, cell biological and genetic studies demonstrate that MIG-17 is secreted from cells like muscles to regulate basement membrane proteins. In the nematode brain, the basement membrane does not directly contact synapses. Instead, muscle-derived basement membrane coats one side of the glia, while glia contact synapses on their other side. MIG-17 modifies the muscle-derived basement membrane to modulate epidermal-glial crosstalk and sustain glia location and morphology during growth. Glia position in turn sustains the synaptic pattern established during embryogenesis. Our findings uncover a muscle-epidermis-glia signaling axis that sustains synaptic specificity during the organism’s allometric growth.
