Control of Asymmetric Neural Stem Cell Division

神经干细胞不对称分裂的控制

基本信息

  • 批准号:
    7152899
  • 负责人:
  • 金额:
    $ 23.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2002
  • 资助国家:
    美国
  • 起止时间:
    2002-12-01 至 2007-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Proper functioning of the brain depends on the coordination of diverse types of neurons and glia, which arise at distinct locations and make intricate connections. Understanding how these brain cells are normally developed holds the key to therapeutic intervention of neurological diseases, especially those with developmental etiology. Neural stem cells (NSCs) play critical roles in generating neurons and gila during both embryonic development and adult life. Despite their clinical importance, little is known about the identity and location of the mammalian NSCs and how their behavior is regulated in vivo. The Drosophila NSCs provide an excellent opportunity for such studies. The long-term goal of this proposal is to understand the molecular and cellular mechanisms regulating the differentiation and self-renewal of NSCs, using cell biological, genetic, and molecular analyses in Drosophila. The Drosophila central nervous system stem cells (neuroblasts) undergo self-renewing asymmetric cell divisions. After each division, one daughter cell remains as a stem cell and the other is committed to differentiation. Determinants whose asymmetric segregation serves to intrinsically alter cell fate choices have been identified. The asymmetric segregation of determinant Numb requires Partner of Numb (Pon) protein. In this proposal, we plan to use Pon as a starting point to achieve a mechanistic understanding of how the asymmetric segregation of cell fate determinants is accomplished. We will first carry out a detailed characterization of the Pon localization domain to identify the molecular features in this domain that contribute to its asymmetric localization and proteins that act through this domain to exert their function. To identify other players that control the localization of Pon, we will test the involvement of myosin motor molecules. We will also perform a forward mutagenesis screen, using a Pon-green fluorescent protein (GFP) reporter as the assay system, to systematically identify key genes that control the asymmetric division of NSCs. Given the conservation of molecular mechanisms that control many developmental processes, it is highly likely that the genes and genetic programs regulating the behavior of NSCs will also be conserved between Drosophila and mammals. We believe that knowledge gained from our study will influence mammalian NSC research and contribute to the understanding and treatment of neurological diseases in humans.
描述(申请人提供):大脑的正常功能依赖于不同类型的神经元和神经胶质的协调,它们出现在不同的位置,并形成复杂的连接。了解这些脑细胞是如何正常发育的,是神经系统疾病,特别是那些发育性病因的治疗干预的关键。神经干细胞(NSCs)在胚胎发育和成人生活中产生神经元和胶质细胞起着至关重要的作用。尽管它们具有重要的临床意义,但人们对哺乳动物NSCs的身份和位置以及它们的行为如何在体内受到调节知之甚少。果蝇NSCs为此类研究提供了极好的机会。本课题的长期目标是通过对果蝇的细胞生物学、遗传学和分子分析,了解调节NSCs分化和自我更新的分子和细胞机制。果蝇中枢神经系统干细胞(成神经细胞)经历自我更新的不对称细胞分裂。每次分裂后,一个子细胞仍然作为干细胞存在,而另一个则致力于分化。已经确定了其不对称分离从本质上改变细胞命运选择的决定因素。决定因子Numb的不对称分离需要Numb的伴侣蛋白(Partner of Numb, Pon)。在这个建议中,我们计划使用Pon作为起点来实现对细胞命运决定因素的不对称分离是如何完成的机制理解。我们将首先对Pon定位域进行详细的表征,以确定该区域中导致其不对称定位的分子特征以及通过该区域发挥其功能的蛋白质。为了确定控制Pon定位的其他参与者,我们将测试肌凝蛋白运动分子的参与。我们还将使用pon -绿色荧光蛋白(GFP)报告基因作为检测系统,进行正向诱变筛选,系统地识别控制NSCs不对称分裂的关键基因。考虑到控制许多发育过程的分子机制的保守性,调节NSCs行为的基因和遗传程序很可能在果蝇和哺乳动物之间也会保守。我们相信,从我们的研究中获得的知识将影响哺乳动物NSC的研究,并有助于理解和治疗人类神经系统疾病。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Bingwei Lu其他文献

Bingwei Lu的其他文献

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{{ truncateString('Bingwei Lu', 18)}}的其他基金

Reverse electron transport and tauopathy
反向电子传递和tau蛋白病
  • 批准号:
    10740115
  • 财政年份:
    2023
  • 资助金额:
    $ 23.42万
  • 项目类别:
A Novel Role of Fragile-X Mental Retardation Protein in Mitochondrial Calcium Homeostasis
Fragile-X 智力迟钝蛋白在线粒体钙稳态中的新作用
  • 批准号:
    10452354
  • 财政年份:
    2022
  • 资助金额:
    $ 23.42万
  • 项目类别:
A Novel Role of Fragile-X Mental Retardation Protein in Mitochondrial Calcium Homeostasis
Fragile-X 智力迟钝蛋白在线粒体钙稳态中的新作用
  • 批准号:
    10612482
  • 财政年份:
    2022
  • 资助金额:
    $ 23.42万
  • 项目类别:
Interplay between amyloid precursor protein metabolism and ER-mitochondria contact
淀粉样蛋白前体蛋白代谢与内质网线粒体接触之间的相互作用
  • 批准号:
    10301076
  • 财政年份:
    2021
  • 资助金额:
    $ 23.42万
  • 项目类别:
Interplay between amyloid precursor protein metabolism and ER-mitochondria contact
淀粉样蛋白前体蛋白代谢与内质网线粒体接触之间的相互作用
  • 批准号:
    10470218
  • 财政年份:
    2021
  • 资助金额:
    $ 23.42万
  • 项目类别:
Understanding SHRF, an RNA exosome-linked disease with multi-organ involvement
了解 SHRF,一种与 RNA 外泌体相关的多器官受累疾病
  • 批准号:
    10305689
  • 财政年份:
    2020
  • 资助金额:
    $ 23.42万
  • 项目类别:
Mitochondrial inner membrane architecture in skeletal muscle pathophysiology
骨骼肌病理生理学中的线粒体内膜结构
  • 批准号:
    10317296
  • 财政年份:
    2020
  • 资助金额:
    $ 23.42万
  • 项目类别:
Mitochondrial inner membrane architecture in skeletal muscle pathophysiology
骨骼肌病理生理学中的线粒体内膜结构
  • 批准号:
    10441283
  • 财政年份:
    2019
  • 资助金额:
    $ 23.42万
  • 项目类别:
Mitochondrial inner membrane architecture in skeletal muscle pathophysiology
骨骼肌病理生理学中的线粒体内膜结构
  • 批准号:
    9979767
  • 财政年份:
    2019
  • 资助金额:
    $ 23.42万
  • 项目类别:
Mitochondrial inner membrane architecture in skeletal muscle pathophysiology
骨骼肌病理生理学中的线粒体内膜结构
  • 批准号:
    10657388
  • 财政年份:
    2019
  • 资助金额:
    $ 23.42万
  • 项目类别:

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