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）：成人大脑中的持久神经发生是一种令人兴奋的现象，因为它有望开发治疗患病和受伤的中枢神经系统（CNS）的治疗剂。不幸的是，如何刺激神经干细胞以增殖和分化为各种细胞类型，以及如何诱导其后代在成人大脑中生存。此外，缺乏在完整的哺乳动物中枢神经系统中这些过程中测试候选基因的快速手段。对于拟议的项目，将在Perrimon Lab中完成的近期全基因组RNA干扰（RNAI）筛选中揭示细胞损失表型的基因将在神经细胞存活，细胞数和分化中检查中的作用。使用神经元，神经胶质和肌肉细胞的果蝇原发性培养物进行屏幕。此独特数据集中的基因是神经细胞特异性增殖，命运或生存力的候选者，因为它们在Perrimon实验室中执行的非神经细胞系中的细胞损失中没有被发现。体内的次要测定和遗传方法将用于确定这些基因的敲低如何带来神经特异性细胞损失。通过利用快速的体内RNAi测定法来测试基因在祖细胞增殖中的作用或小鼠视网膜中的生存，将立即应用于脊椎动物神经发生的研究。预计这项研究将导致在视网膜变性的情况下发现新的干预治疗靶标，并且可能具有更广泛的影响脑损伤和疾病。