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

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.

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Author details

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
    ORCID icon "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.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: February 10, 2020
  2. Accepted: April 5, 2020
  3. Accepted Manuscript published: April 7, 2020 (version 1)
  4. 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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  1. Jiale Fan
  2. Tingting Ji
  3. Kai Wang
  4. Jichang Huang
  5. Mengqing Wang
  6. Laura Manning
  7. Xiaohua Dong
  8. Yanjun Shi
  9. Xumin Zhang
  10. Zhiyong Shao
  11. Daniel A Colón-Ramos
(2020)
A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in C. elegans
eLife 9:e55890.
https://doi.org/10.7554/eLife.55890

Share this article

https://doi.org/10.7554/eLife.55890

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