1. A muscle-epidermis-glia signaling axis sustains synaptic specificity during allometric growth in Caenorhabditis elegans .
- Author
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Fan J, Ji T, Wang K, Huang J, Wang M, Manning L, Dong X, Shi Y, Zhang X, Shao Z, and Colón-Ramos DA
- Subjects
- Animals, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins physiology, Disintegrins genetics, Disintegrins physiology, Embryonic Development, Epidermal Cells physiology, Metalloendopeptidases genetics, Metalloendopeptidases physiology, Proteomics, Caenorhabditis elegans growth & development, Epidermis physiology, Muscles physiology, Neuroglia physiology, Signal Transduction, Synapses physiology
- 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., Competing Interests: JF, TJ, KW, JH, MW, LM, XD, YS, XZ, ZS, DC No competing interests declared, (© 2020, Fan et al.)
- Published
- 2020
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