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.
Article and author information
Author details
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.
Reviewing Editor
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
Publication history
- Received: February 10, 2020
- Accepted: April 5, 2020
- Accepted Manuscript published: April 7, 2020 (version 1)
- Version of Record published: April 17, 2020 (version 2)
Copyright
© 2020, Fan et al.
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.
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