1. Neuroscience

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
https://doi.org/10.7554/eLife.55890
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

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

  • 1,755
    views
  • 341
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  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

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Single-cell transcriptomics of vomeronasal neuroepithelium reveals a differential endoplasmic reticulum environment amongst neuronal subtypes

    GVS Devakinandan, Mark Terasaki, Adish Dani
    Research Article

    Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns, and functional differences amongst neurons, we performed single-cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each, which we made available as a searchable web resource accessed from https://www.scvnoexplorer.com. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. In addition, differences in ER content and prevalence of cubic membrane ER ultrastructure revealed by electron microscopy, indicate fundamental differences in ER function.

    1. Developmental Biology
    2. Neuroscience

    A human forebrain organoid model reveals the essential function of GTF2IRD1-TTR-ERK axis for the neurodevelopmental deficits of Williams syndrome

    Xingsen Zhao, Qihang Sun ... Xuekun Li
    Research Article

    Williams syndrome (WS; OMIM#194050) is a rare disorder, which is caused by the microdeletion of one copy of 25–27 genes, and WS patients display diverse neuronal deficits. Although remarkable progresses have been achieved, the mechanisms for these distinct deficits are still largely unknown. Here, we have shown that neural progenitor cells (NPCs) in WS forebrain organoids display abnormal proliferation and differentiation capabilities, and synapse formation. Genes with altered expression are related to neuronal development and neurogenesis. Single cell RNA-seq (scRNA-seq) data analysis revealed 13 clusters in healthy control and WS organoids. WS organoids show an aberrant generation of excitatory neurons. Mechanistically, the expression of transthyretin (TTR) are remarkably decreased in WS forebrain organoids. We have found that GTF2IRD1 encoded by one WS associated gene GTF2IRD1 binds to TTR promoter regions and regulates the expression of TTR. In addition, exogenous TTR can activate ERK signaling and rescue neurogenic deficits of WS forebrain organoids. Gtf2ird1-deficient mice display similar neurodevelopmental deficits as observed in WS organoids. Collectively, our study reveals critical function of GTF2IRD1 in regulating neurodevelopment of WS forebrain organoids and mice through regulating TTR-ERK pathway.

    1. Computational and Systems Biology
    2. Neuroscience

    Estradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances

    Jian Qiu, Margaritis Voliotis ... Martin J Kelly
    Research Article

    Hypothalamic kisspeptin (Kiss1) neurons are vital for pubertal development and reproduction. Arcuate nucleus Kiss1 (Kiss1ARH) neurons are responsible for the pulsatile release of gonadotropin-releasing hormone (GnRH). In females, the behavior of Kiss1ARH neurons, expressing Kiss1, neurokinin B (NKB), and dynorphin (Dyn), varies throughout the ovarian cycle. Studies indicate that 17β-estradiol (E2) reduces peptide expression but increases Slc17a6 (Vglut2) mRNA and glutamate neurotransmission in these neurons, suggesting a shift from peptidergic to glutamatergic signaling. To investigate this shift, we combined transcriptomics, electrophysiology, and mathematical modeling. Our results demonstrate that E2 treatment upregulates the mRNA expression of voltage-activated calcium channels, elevating the whole-cell calcium current that contributes to high-frequency burst firing. Additionally, E2 treatment decreased the mRNA levels of canonical transient receptor potential (TPRC) 5 and G protein-coupled K+ (GIRK) channels. When Trpc5 channels in Kiss1ARH neurons were deleted using CRISPR/SaCas9, the slow excitatory postsynaptic potential was eliminated. Our data enabled us to formulate a biophysically realistic mathematical model of Kiss1ARH neurons, suggesting that E2 modifies ionic conductances in these neurons, enabling the transition from high-frequency synchronous firing through NKB-driven activation of TRPC5 channels to a short bursting mode facilitating glutamate release. In a low E2 milieu, synchronous firing of Kiss1ARH neurons drives pulsatile release of GnRH, while the transition to burst firing with high, preovulatory levels of E2 would facilitate the GnRH surge through its glutamatergic synaptic connection to preoptic Kiss1 neurons.