Department of Neurosurgery, the State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, the Institutes of Brain Science, and Zhongshan Hospital, Fudan University Shanghai, Shanghai, China.
State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China.
Elife. 2020 Apr 7;9:e55890. doi: 10.7554/eLife.55890.
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 for regulators of this process and identified , 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.
突触位置是精确的电路连接的基础。突触位置可以在胚胎发生过程中建立，并在生长过程中维持。在异速生长过程中维持突触特异性的机制在很大程度上尚不清楚。我们在 中进行了正向遗传筛选，以寻找调节这一过程的调节剂，并鉴定出 ，一种保守的 ADAMTS 金属蛋白酶。蛋白质组学质谱分析、细胞生物学和遗传学研究表明，MIG-17 像肌肉细胞一样分泌，以调节基底膜蛋白。在线虫大脑中，基底膜并不直接接触突触。相反，肌肉衍生的基底膜覆盖神经胶质的一侧，而神经胶质在另一侧接触突触。MIG-17 修饰肌肉衍生的基底膜，以调节表皮-神经胶质的串扰，并在生长过程中维持神经胶质的位置和形态。反过来，神经胶质的位置维持了胚胎发生过程中建立的突触模式。我们的发现揭示了一个肌肉-表皮-神经胶质信号轴，它在生物体的异速生长过程中维持突触特异性。
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