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.

中文翻译：

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肌肉-表皮-神经胶质信号轴在秀丽隐杆线虫异速生长期间维持突触特异性

突触位置是精确电路连接的基础。突触位置可以在胚胎发生期间建立并在生长期间维持。在异速生长期间维持突触特异性的机制在很大程度上是未知的。我们在秀丽隐杆线虫中对这一过程的调节剂进行了正向遗传筛选，并鉴定了 mig-17，一种保守的 ADAMTS 金属蛋白酶。蛋白质组学质谱、细胞生物学和遗传研究表明，MIG-17 从肌肉等细胞分泌，以调节基底膜蛋白。在线虫大脑中，基底膜不直接接触突触。相反，肌肉衍生的基底膜覆盖在胶质细胞的一侧，而胶质细胞则在另一侧接触突触。MIG-17 修饰肌肉衍生的基底膜以调节表皮-神经胶质串扰并在生长过程中维持神经胶质的位置和形态。神经胶质位置反过来维持胚胎发生过程中建立的突触模式。我们的研究结果揭示了一个肌肉-表皮-神经胶质信号轴，该轴在生物体异速生长期间维持突触特异性。