RNAi Analysis of Neural Cell Proliferation and Viability

神经细胞增殖和活力的 RNAi 分析

• 批准号: 7054596
• 负责人: MARY C PACKARD
• 金额: $ 4.6万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054596
• 关键词: Drosophilidae; RNA interference; Wnt gene /protein; apoptosis; arthropod genetics; axon; cell differentiation; cell migration; cell proliferation; central nervous system; functional /structural genomics; genetically modified animals; glycoproteins; growth cones; high throughput technology; laboratory mouse; neural fasciculation; neurogenetics; neuronal guidance; postdoctoral investigator; protein structure function; protein tyrosine kinase; retina

DESCRIPTION (provided by applicant): Persistant neurogenesis in the adult brain is an exciting phenomena because of the promise it holds for developing therapeutics to treat diseased and injured central nervous systems (CNS). Unfortunately, how neural stem cells are stimulated to proliferate and differentiate into a various cell types and how their progeny can be induced to survive in the adult brain are not understood. Moreover, rapid means for testing candidate genes in these processes in the intact mammalian CNS are lacking. For the proposed project, genes whose knock down revealed cell loss phenotypes in a recent genome-wide RNA interference (RNAi) screen accomplished in the Perrimon lab will be examined for roles in neural cell survival, cell number, and differentiation. The screen was performed using Drosophila primary cultures of neurons, glia, and muscle cells.(K. Sepp and N. Perrimon, in preparation). Genes in this unique data set are candidates for neural-cell specific proliferation, fate determination, or viability because they were not uncovered in more general screens for cell loss in non-neural cell lines performed in the Perrimon laboratory. Secondary assays and genetic approaches in vivo will be used to identify how knockdown of these genes brings about neural-specific cell loss. Findings will be immediately applied to studies of vertebrate neurogenesis by taking advantage of a rapid in vivo RNAi assay to test the genes for roles in progenitor cell proliferation or survival in the mouse retina. This study is expected to lead to the discovery of novel therapeutic targets for intervention in cases of retinal degeneration and may have more widespread implications brain injury and disease.

描述（由申请人提供）：成人大脑中的持续神经发生是一种令人兴奋的现象，因为它有望开发出治疗患病和受伤的中枢神经系统（CNS）的疗法。不幸的是，如何刺激神经干细胞增殖并分化成各种细胞类型以及如何诱导它们的后代在成人大脑中存活尚不清楚。此外，缺乏在完整哺乳动物中枢神经系统中测试这些过程中候选基因的快速方法。在拟议的项目中，Perrimon 实验室最近完成的全基因组 RNA 干扰 (RNAi) 筛选中，敲低揭示细胞损失表型的基因将被检查在神经细胞存活、细胞数量和分化中的作用。该筛选是使用果蝇神经元、神经胶质细胞和肌肉细胞的原代培养物进行的。（K. Sepp 和 N. Perrimon，正在准备中）。这个独特数据集中的基因是神经细胞特异性增殖、命运决定或活力的候选基因，因为在 Perrimon 实验室进行的非神经细胞系细胞损失的更一般筛选中没有发现它们。体内二次测定和遗传方法将用于确定这些基因的敲除如何导致神经特异性细胞损失。研究结果将立即应用于脊椎动物神经发生的研究，通过利用快速体内 RNAi 测定来测试基因在小鼠视网膜中祖细胞增殖或存活中的作用。这项研究有望发现用于干预视网膜变性病例的新治疗靶点，并可能对脑损伤和疾病产生更广泛的影响。