PAX6-induced adult neurogenesis

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.