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

Jiale Fan | Tingting Ji | Kai Wang | Jichang Huang | Mengqing Wang | Laura Manning | Xiaohua Dong | Yanjun Shi | Xumin Zhang | Zhiyong Shao | Daniel A Colón-Ramos
eLife | 2020

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.

Pubmed ID: 32255430

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS076558
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK045735
  • Agency: NINDS NIH HHS, United States
    Id: DP1 NS111778

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