神经干细胞NSCs移植治疗脊髓损伤SCI是研究热点，而调控NSCs向损伤区迁移是未解决的难题。我们首次发现趋化因子受体甲酰基肽受体FPRs表达于NSCs并能趋化后者向脑内损伤区迁移，且与Actin结合蛋白Anillin-1 （ANI-1）表达水平相关，表明FPRs可能通过上调ANI-1趋化NSCs，但其信号通路仍不明确。预实验和生物信息学发现Rac磷酸化可能是ANI-1上游的重要信号通路。那么，FPR是否通过Rac通路活化ANI-1与Actin结合，进而改变NSC骨架结构促进其迁移？为证实推测，本项目拟使用基因敲除及转基因小鼠、活细胞动态摄影、特异性信号阻断等技术，在体内外探明FPRs作用下NSCs趋化、分布规律；明确FPRs通过Rac通路活化ANI-1及Actin极性分布促进NSCs迁移的关键胞内机制，为NSCs移植治疗SCI等中枢神经系统创伤性疾病提供实验依据和潜在治疗靶点。

Transplantation of neural stem cells (NSCs) is one of promising therapy strategies for spinal cord injury (SCI). However, the key unsolved limitation of transplanted NSCs is their insufficient migrating ability to the lesion site. Chemokine receptors play pivotal roles in the migration of NSCs through initiating intracellular signaling pathway and subsequently remodeling the cytoskeleton upon ligation with their ligands. The underlying mechanism remains unknow. Our previous study found, for the first time, that chemokine receptors, formylpeptide receptors (FPRs) were expressed by NSCs and potently mediated the cells to migrate to SCI lesion site, which is accompanied by upregulation of F-actin and its binding protein Anillin-1. Our study also discovered that Rac, one upstream signal molecule of Anillin-1, was upregulated in the migrating NSCs. Thus, we hypothesize that FPRs activate F-actin binding protein Anillin-1 through Rac pathway to remodel the cytoskeleton of NSCs, resulting in directed NSC migration to SCI lesion site and to promote neural function recovery. By using FPR knockout mouse model, specific pathway blockage methods and live cell photography in this study, we aim to illustrate the possible mechanisms underlying regulation of NSCs migration, and this will provide experimental basis and therapeutic targets for SCI treatment.