During the development of mammalian neuromuscular junction (NMJ), the original supernumerary axon inputs are gradually eliminated, finally leaving each muscle fiber innervated by a single axon terminal. However, the molecular cues that mediate the elimination of redundant axon inputs remain unclear. Here we show that tumor necrosis factor-α (TNFα) expressed in postsynaptic muscle cells plays an important role in presynaptic axonal elimination at the NMJ. We found that intramuscular injection of TNFα into the levator auris longus (LAL) muscles caused disassociation of presynaptic nerve terminals from the postsynaptic acetylcholine receptor (AChR) clusters. By contrast, genetic ablation of TNFα globally or specifically in skeletal muscle cells, but not in motoneurons or Schwann cells, delayed the synaptic elimination. Moreover, ablation of TNFα in muscle cells attenuated the tendency of activity-dependent competition in a motoneuron–muscle coculture system. These results suggest a role of postsynaptic TNFα in the elimination of redundant synaptic inputs.

在哺乳动物神经肌肉接头（NMJ）的发育过程中，原来多余的轴突输入逐渐消除，最终留下每根肌纤维由单个轴突末端支配。然而，介导消除多余轴突输入的分子线索仍不清楚。在这里，我们表明突触后肌细胞中表达的肿瘤坏死因子-α (TNFα) 在 NMJ 的突触前轴突消除中发挥重要作用。我们发现，将 TNFα 肌肉注射到提耳长肌 (LAL) 会导致突触前神经末梢与突触后乙酰胆碱受体 (AChR) 簇分离。相比之下，整体或特定于骨骼肌细胞（而非运动神经元或雪旺细胞）的 TNFα 基因消除延迟了突触消除。此外，肌肉细胞中 TNFα 的消除减弱了运动神经元-肌肉共培养系统中活动依赖性竞争的趋势。这些结果表明突触后 TNFα 在消除冗余突触输入中发挥作用。