A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in C. elegans

Abstract
Data availability
Article and author information
Metrics

Abstract

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.

Data availability

All data is presented in the figures or supplementary figures

Article and author information

Author details

Jiale Fan

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Tingting Ji

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Kai Wang

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Jichang Huang

State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Mengqing Wang

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Laura Manning

Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Xiaohua Dong

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Yanjun Shi

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Xumin Zhang

State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Zhiyong Shao

Department of Neurosurgery, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science and the Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

For correspondence
shaozy@fudan.edu.cn

Competing interests
The authors declare that no competing interests exist.
Daniel A Colón-Ramos

Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, New Haven, United States

For correspondence
daniel.colon-ramos@yale.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0223-7717

Funding

National Natural Science Foundation of China (31471026,31872762)

Jiale Fan
Tingting Ji
Kai Wang
Jichang Huang
Mengqing Wang
Xiaohua Dong
Yanjun Shi
Xumin Zhang
Zhiyong Shao

NIH Office of the Director (DP1NS111778)

Laura Manning
Daniel A Colón-Ramos

National Institutes of Health (R01NS076558)

Laura Manning
Daniel A Colón-Ramos

Howard Hughes Medical Institute (Faculty Scholar)

Daniel A Colón-Ramos

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

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.