神经元内在再生能力的激活是周围神经损伤再生的关键因素，我们通过损伤后能再生和部分恢复功能的坐骨神经来寻找维持神经元存活、促进神经再生的关键调控分子。利用体外模型培养不同时间点大鼠DRG神经元，模拟轴突损伤再生，系统性分析、功能验证得到轴突再生过程中的关键差异基因FEZF2。同时发现其存在转录后调控，结合生物信息学分析，找到了调控FEZF2的非编码小RNA miR-204-3p。本课题将进一步明确FEZF2抑制促进DRG神经元突起再生的作用及其下游机制，以及阐明miRNA-204-3p靶向FEZF2参与神经元功能的调节；鞘内注射针对FEZF2的AAV5型干扰病毒、过表达miR-204-3p的AAV5病毒、miR-204-3p病毒联合过表达FEZF2 编码区的AAV5病毒，用人工组织神经移植物桥接修复大鼠缺损坐骨神经，在体观察轴突再生和神经修复的效果，探讨FEZF2作为新靶点的应用价值。

The peripheral nervous system (PNS) has an intrinsic capacity to regenerate on its own. Deciphering the molecular mechanisms underlying nerve regeneration following rat sciatic nerve transection contributes to identifying the triggers and regulators of nerve regeneration. Dorsal root ganglia (DRG) neurons spontaneously undergo robust neurite growth after axotomy. In preliminary experiments, we (1) systematically screened mRNA profiling in couple with miRNA profiling in DRGs neuron during neurite outgrowth in vitro,(2) performed functional investigation by using in vitro cell model, and noted that FEZF2 inhibition markedly promoted neurite outgrowth.In this project, we are going to search for the downstream factor that could be regulated by FEZF2, and to explore the molecular mechanisms of miR-204-3p promoting regenerative outgrowth of DRG neurons by targeting FEZF2. Moreover, we also plan to investigate the impact of FEZF2 inhibition in an in vivo model by intrathecal injection with AAV5 to determine whether the exposure to FEZF2 shRNA or miR-204-3p could enhance axon growth. We believe that the oncoming findings may aid to developing a new route to stimulate intrinsic neurite growth in peripheral nerve regeneration.