Molecular mechanisms underlying adult SVZ neurogenesis

成人 SVZ 神经发生的分子机制

• 批准号: 7056943
• 负责人: Minoree Kohwi
• 金额: $ 3.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056943
• 关键词: dopamine; gene expression; interneurons; laboratory mouse; nerve stem cell; neurogenesis; neuroregulation; olfactory lobe; predoctoral investigator; tissue /cell culture; transcription factor

DESCRIPTION (provided by applicant): Neural stem cells reside in the subventricular zone (SVZ) of adult mammals continuously producing multiples types of olfactory bulb (OB) interneurons. The generation of diverse types of neurons within the adult brain must be tightly regulated in order to maintain a functional circuit with high turnover of its neuronal components; however, the molecular mechanism underlying generation of such diversity is unknown. Our recent data shows that the transcription factor Pax6 is required for the generation of dopaminergic OB interneurons. The expression of another factor Er81 in a distinct pattern from Pax6 in the adult OB suggests that different transcriptional machineries may function in the production of OB interneuron subtypes. In this application, we aim to determine which OB interneuron subtype requires Er81. We also plan to analyze which embryonic progenitor zones can contribute to OB neurogenesis to gain insight into the molecular players of adult neuronal diversity. Thirdly, we aim to compare the molecular expression profiles of adult neural stem cells. Understanding the mechanism underlying neuronal diversity within the brain will be important for future therapies to replace damaged neurons in diseases and trauma.

描述（由申请人提供）：神经干细胞驻留在成年哺乳动物的室室（SVZ）中，不断产生倍数的嗅球（OB）中间神经元的类型。必须严格调节成人大脑内不同类型的神经元的产生，以维持其神经元成分较高的功能电路；但是，这种多样性产生的分子机制尚不清楚。我们最近的数据表明，生成多巴胺能OB中间神经元需要转录因子PAX6。在成年OB中与PAX6不同模式中另一种因子ER81的表达表明，不同的转录机器可能在OB间neuron亚型的产生中起作用。在此应用程序中，我们旨在确定哪种OB间神经元亚型需要ER81。我们还计划分析哪些胚胎祖细胞区可以有助于神经发生，以深入了解成人神经元多样性的分子参与者。第三，我们旨在比较成年神经干细胞的分子表达谱。了解大脑内神经元多样性的机制对于将来替代疾病和创伤中受损的神经元受损的疗法非常重要。