1. Neuroscience
Download icon

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

  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  Is a corresponding author
  11. Daniel A Colón-Ramos  Is a corresponding author
  1. Fudan University, China
  2. Yale University School of Medicine, United States
Research Article
  • Cited 3
  • Views 1,219
  • Annotations
Cite this article as: eLife 2020;9:e55890 doi: 10.7554/eLife.55890

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

  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

Publication 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.

Metrics

  • 1,219
    Page views
  • 266
    Downloads
  • 3
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Weisheng Wang et al.
    Research Article Updated

    Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human functional magnetic resonance imaging data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

    1. Neuroscience
    Stanley Heinze et al.
    Tools and Resources Updated

    Insect neuroscience generates vast amounts of highly diverse data, of which only a small fraction are findable, accessible and reusable. To promote an open data culture, we have therefore developed the InsectBrainDatabase (IBdb), a free online platform for insect neuroanatomical and functional data. The IBdb facilitates biological insight by enabling effective cross-species comparisons, by linking neural structure with function, and by serving as general information hub for insect neuroscience. The IBdb allows users to not only effectively locate and visualize data, but to make them widely available for easy, automated reuse via an application programming interface. A unique private mode of the database expands the IBdb functionality beyond public data deposition, additionally providing the means for managing, visualizing, and sharing of unpublished data. This dual function creates an incentive for data contribution early in data management workflows and eliminates the additional effort normally associated with publicly depositing research data.