PAX6-induced adult neurogenesis

细胞命运由主控调节器控制，神经系统也是如此。Pax6是一种高度保守的 转录因子由两个DNA结合区和一个转录激活区组成。它是宽泛的 在神经干细胞/前体细胞中表达，在神经元的特化、迁移和轴突中发挥关键作用 投射。通过一系列体内筛选，我们发现PAX6也能够诱导新的 来自成年小鼠脊髓神经胶质细胞的基因追踪神经元。基于这些令人振奋的数据，我们 假设PAX6诱导的成体神经再生可能是另一种策略 用于神经再生。本项目的主要目标是研究PAX6诱导的成人神经发生的特征。 并确定其在创伤性神经损伤后的功能作用。我们提出了三个具体目标来 实现这一目标。首先，我们将利用遗传谱系追踪和全基因组深度测序来 了解PAX6如何从成年小鼠脊髓中驻留的神经胶质细胞诱导新的神经元。第二， 我们将使用重组病毒介导的跨突触追踪来描绘PAX6- 诱导出新的神经元。第三，我们将使用化学遗传学来梳理PAX6诱导的功能作用 新神经元对创伤成年小鼠行为的影响。

Cell fate is controlled by master regulators, as is also the case in the nervous system. Pax6 is a highly conserved transcription factor consisting of two DNA-binding domains and a transcriptional activation domain. It is broadly expressed in neural stem/progenitor cells and plays pivotal roles in neuronal specification, migration, and axonal projections. Through a series of in vivo screens, we discovered that PAX6 is also capable of inducing new neurons from genetically traced glial cells in the adult mouse spinal cord. Based on such exciting data, we hypothesize that PAX6-induced adult neurogenesis from resident glial cells may represent an alternative strategy for neural regeneration. The major goal of this project is to characterize the PAX6-induced adult neurogenesis process and determine its functional role following traumatic neural injuries. We propose three specific aims to accomplish this goal. First, we will employ genetic lineage tracing and genome-wide deep sequencing to understand how PAX6 induces new neurons from resident glial cells in the adult mouse spinal cord. Secondly, we will employ recombinant virus-mediated transsynaptic tracing to delineate the network connections of PAX6- induced new neurons. And thirdly, we will use chemogenetics to tease out the functional role of PAX6-induced new neurons on behavior in adult mice with traumatic injury.