脊神经根性撕脱伤术后轴突再生能力不足是功能重建的瓶颈问题，目前缺乏促进轴突再生的靶标。研究报道Celsr基因在神经发育中至关重要，但其是否影响神经再生修复不清楚。我们预实验发现：成年脊髓运动神经元维持钙黏连素受体Celsr2高表达；臂丛撕脱运动根再植模型中，Celsr2-/-小鼠呈现较对照组更好的轴突再生和功能恢复；Celsr2敲除能促进培养脊髓运动神经元轴突成束化和生长。鉴于此，我们提出：Celsr2可能是调控脊髓运动神经元轴突再生的关键靶点，抑制Celsr2表达可作为根性撕脱伤运动根再植术的一个重要干预措施。我们拟构建运动神经元Celsr2条件敲除小鼠和应用Celsr2-shRNA敲减技术，在臂丛撕脱运动根再植模型分析特异性Celsr2功能抑制对轴突再生和功能重建影响，并结合组织培养、分子生物学等阐明Celsr2的作用机理。预期结果将为运动神经元疾病的治疗提供分子干预靶点奠定理论基础。

The insufficient axon regeneration ability is a key problem in clinical neural repair and functional reconstruction after spinal root avulsion. At present, there is no effective intervention molecular target to promote axon regeneration of spinal motor neurons after injuries. It is reported that Celsr genes play important roles in neural development, but their contribution to axonal regeneration and neural repair remains unknown. In our preliminary experiments, we found that cadherin receptor protein Celsr2 maintained high expression in adult spinal motoneurons; using brachial plexus avulsion and motor root re-implantation model, we found that Celsr2-/- mice harbored better axonal regeneration and forelimb function recovery than the control animals; and Celsr2 knockout could favor axonal bundle formation and growth in cultured spinal motoneurons. Thus, we hypothesized that Celsr2 may be a potential molecular target for regulating axonal regeneration of spinal motoneurons, and inhibiting Celsr2 function may be an important adjuvant therapy for motor root re-implantation after motor root avulsion. To test this hypothesis, we will conditionally knockout Celsr2 in spinal motoneurons by generating mutant animals or knockdown Celsr2 using Celsr2-shRNA virus, and evaluate the effects of cell and time-specific inhibition of Celsr2 function on axon regeneration and functional recovery in brachial plexus avulsion and motor root re-implantation animal models. In addition, we will study the potential mechanisms of Celsr2 roles involved in axon regeneration using tissue culturing and molecular biological techniques. This work will contribute to exploring the molecular intervention targets and providing the basic knowledge for the treatment of motor neuron diseases.