传统认为成年大脑皮质无神经元发生，近年发现缺血后可有新生神经元。主流观点认为新生神经元来自侧脑室下区，皮质原位能否产生神经元一直存有争议。我们发现成年小鼠皮质缺血后有快速的神经元新生，新生神经元主要来自损伤区局部的Nestin+细胞，但具体的细胞来源及发生机制仍不清楚。由于正常皮质部分星形胶质细胞表达Sox2，后者是缺血后皮质Nestin+细胞的主体，结合文献与初步结果，我们推测：Sox2+星形胶质细胞可能是新生神经元的主要来源，Wnt2/β-catenin信号诱导的Sox2+星形胶质细胞去分化可能是神经元发生的主要机制。本项目将采用基于Split-Cre的细胞谱系追踪、前体细胞剔除、细胞培养等方法验证上述推测，并从Sox2+星形胶质细胞中神经元前体细胞关键转录因子Mash1表达调控的角度探讨去分化的分子机制，以期阐明皮质缺血后原位神经元新生的来源与机制，为脑缺血的修复/治疗提供新的思路。

Adult cortex has long been thought as “non-neurogenic”. Recent studies have reported neurogenesis in cortex after ischemia. The post-ischemic new-born neurons were regarded by most researchers as the progenies of adult neural stem cells in the subventricular zone which migrated to the lesion site. Whether in situ neurogenesis could occur is still under controversial. We found a rapid neurognenesis in the adult cortex after focal ischemia. Our data suggest that new neurons are mainly derived from local Nestin-positive cells. However, the authentic identity of the neurogenic cells and underlying mechanisms for this neurogenesis remain unclear. Considering the expression of Sox2 in a sub-population of astoryctes, and the fact that Sox2-positive astrocytes are the major cell type of Nestin-positve cells, we propose here, based on literature and our preliminary study that : Sox2-positive astrocytes may be the major contributor of local neurogenesis after ischemia. Wnt2/β-catenin signaling induced dedifferentiation of Sox2-positive astrocytes may account for the ischemia-induced cortical neurogenesis. In the present project, we will testify this hypothesis by by Split-Cre mediated cell-fate tracing, progenitor ablation and cell culture, and investigate the mechanism of dedifferentiation through coordinate regulation of Mash1, a pro-neuronal transcription factor in Sox2-positive astrocytes. Thereby, we wish to identify the potential neurogenic cells in adult cortex of mice and reveal the mechanism of ischemia-induced neurogenesis, hoping to promote the recovery of ischemic stroke by enhancing cortical neurogenesis through Wnt signaling.