外周神经系统（PNS）具有再生能力，但临床上促进PNS完全恢复并未彻底解决。Lrp4是单次跨膜的低密度脂蛋白受体，在神经肌肉接头（NMJ）形成与维持中发挥关键作用，敲除小鼠的运动神经元（MN）轴突在NMJ处过度生长。我们预实验发现，特异性敲除施万细胞（SC）Lrp4显著促进坐骨神经的轴突再生，提示Lrp4可能是轴突再生的抑制因子，然而相关的分子机制仍不清楚。本项目以坐骨神经损伤为模型：首先，利用MN或SC特异性敲除小鼠验证SC上Lrp4抑制轴突生长的重要性；其次，利用Lrp4胞内段或胞外段缺失小鼠来确认抑制轴突再生的主要结构域；进一步，在特异性敲除SC上Lrp4的小鼠中过表达Lrp4的不同结构域，找到Lrp4抑制轴突生长的关键结构域，探索可能的信号通路；最后，在野生小鼠中阻断相关信号通路以促进神经再生。本研究有助于了解Lrp4调节轴突再生的分子机制，为加快PNS再生提供新的思路。

The peripheral nervous system (PNS) has regenerative capacity, but the complete recovery of PNS in the clinic has not been solved. Lrp4 is a single transmembrane low-density lipoprotein receptor that plays a key role in the formation and maintenance of neuromuscular junctions (NMJ). It has been reported that Lrp4 knockout leads to excessive growth of motor neuron (MN) axons at NMJ, and our preliminary results also show that specific knockout of Schwann cells (SC) Lrp4 significantly promoted axonal regeneration of the sciatic nerve. These suggests that Lrp4 may be an inhibitor of axonal regeneration, but the molecular mechanisms involved remain unclear. This project uses sciatic nerve injury as a model: first, MN or SC-specific knockout mice were used to verify the importance of SC Lrp4 in inhibiting axon growth; secondly, mice lacking Lrp4 intracellular or extracellular segments were identified to confirm the major domains that inhibit axonal regeneration; further, different Lrp4 mutants were overexpressed in mice specifically knocking out SC Lrp4, exploring possible signaling pathways; finally, blocking related signaling pathways in wild mice to promote sciatic nerve regeneration. This study will be helpful to understand the molecular mechanism of Lrp4 regulation of axonal regeneration and provide new ideas for accelerating PNS regeneration.