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PAX6-induced adult neurogenesis

PAX6诱导的成体神经发生

基本信息

批准号：
10537755
负责人：
Chun-Li Zhang
金额：
$ 48.05万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10537755
关键词：
Adult Animals Astrocytes Axon Behavior Biological Process Brain CSPG4 gene Cell Transplantation Cell physiology Cells ChIP-seq Cicatrix Clinical DNA Binding Domain Data Environment Genetic Goals Immune Injury Laboratories Lead Mediating Modeling Molecular Motor Mus Nerve Degeneration Nerve Regeneration Nervous system structure Neuraxis Neuroglia Neurons Outcome Pathologic Patients Play Population Process Proliferating Rabies virus Recombinants Recovery of Function Research Role Series Signal Pathway Spinal Cord Spinal cord injury Stem Cell Factor Synapses Transcriptional Activation Domain Traumatic injury Vesicular stomatitis Indiana virus Work adult neurogenesis base deep sequencing functional improvement genome-wide in vivo injury recovery mad itch virus migration mouse model nerve injury neural circuit neural repair neurogenesis neuron loss neuronal excitability neuronal survival neurotrophic factor patch clamp postsynaptic presynaptic recombinant virus regenerative therapy relating to nervous system repaired response single-cell RNA sequencing stem stem cells transcription factor tumorigenesis

项目摘要

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.

细胞命运由主调节器控制，神经系统也是如此。Pax 6是一个高度保守的一种转录因子，由两个DNA结合结构域和转录激活结构域组成。人们普遍在神经干/祖细胞中表达，并在神经元的特化、迁移和轴突生长中起关键作用。预测。通过一系列的体内筛选，我们发现PAX 6也能够诱导新的神经元来自成年小鼠脊髓中遗传追踪的神经胶质细胞。基于这些令人兴奋的数据，我们假设PAX 6诱导的来自驻留神经胶质细胞的成体神经发生可能代表一种替代策略神经再生本项目的主要目标是表征PAX 6诱导的成人神经发生处理并确定其在创伤性神经损伤后的功能作用。我们提出三个具体目标，实现这一目标。首先，我们将采用遗传谱系追踪和全基因组深度测序，了解PAX 6如何从成年小鼠脊髓中的常驻胶质细胞诱导新的神经元。第二、我们将采用重组病毒介导的跨突触追踪来描绘PAX 6- 诱导新的神经元。第三，我们将使用化学遗传学来梳理PAX 6诱导的功能作用。新生神经元对创伤性成年小鼠行为的影响。