Molecular/genetic control of oligodendrocyte development

少突胶质细胞发育的分子/遗传控制

基本信息

  • 批准号:
    6852696
  • 负责人:
  • 金额:
    $ 30.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-03-01 至 2008-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this study is to understand the molecular mechanisms that control the specification and differentiation of oligodendrocytes. Although considerable insights have been gained into the molecular mechanisms that control the initial specification of oligodendrocytes, it is still not clear how the terminal differentiation and myelination of oligodendrocytes are regulated during animal development. Recently, we have demonstrated that oligodendrocyte progenitor cells start to acquire the expression of Nkx2.2 homeodomain transcription factor during their migration to their destination sites, and expression of Nkx2.2 is required for oligodendrocyte differentiation and myelin gene expression. Here we hypothesize that Nkx2.2 plays a key role in controlling the timing of oligodendrocyte differentiation and myelination during animal development, and the expression and activity of Nkx2.2 are tightly regulated by both intracellular and extracellular factors. Specific aim 1 of this proposal is to test the hypothesis that Nkx2.2 and Sox10 interact physically and have synergistic actions on activating myelin gene expression and oligodendrocyte differentiation. Specific aim 2 is to test the hypothesis that Nkx2.2 expression in oligodendrocyte progenitor cells can be induced by extracellular factors (thyroid hormone) that promote oligodendrocyte differentiation. Specific aim 3 is to test the hypothesis that the Notch pathway controls the timing of oligodendrocyte differentiation by regulating Nkx2.2 expression in oligodendrocyte progenitor cells. Specific aim 4 is to test the hypothesis that Nkx2.2 regulates oligodendrocyte myelination at later stages of animal life in collaboration with Nkx6.2. Results derived from the proposed studies will significantly enhance our understanding of the genetic circuitry governing the early specification and differentiation of oligodendrocytes, and may provide theoretic basis for design of novel therapeutic approaches for prevention and treatment of motor neuron and oligodendrocyte atrophies.
描述(申请人提供):本研究的长期目标是了解控制少突胶质细胞特化和分化的分子机制。虽然已经对控制少突胶质细胞初始规格的分子机制有了相当大的了解,但仍然不清楚在动物发育过程中少突胶质细胞的终末分化和髓鞘形成是如何调节的。最近,我们发现少突胶质前体细胞在向其目的部位迁移的过程中开始获得Nkx2.2同源区域转录因子的表达,而Nkx2.2的表达是少突胶质细胞分化和髓鞘基因表达所必需的。我们推测,在动物发育过程中,Nkx2.2在控制少突胶质细胞分化和髓鞘形成的时机中起着关键作用,并且Nkx2.2的表达和活性受到细胞内和细胞外因素的严格调控。 这项建议的具体目的1是验证Nkx2.2和Sox10在激活髓鞘基因表达和少突胶质细胞分化方面存在物理相互作用并具有协同作用的假设。具体目的2是验证Nkx2.2在少突胶质细胞前体细胞中的表达可以被促进少突胶质细胞分化的细胞外因子(甲状腺激素)诱导的假说。具体目的3是验证Notch通路通过调节少突胶质前体细胞中Nkx2.2的表达来控制少突胶质细胞分化的时间这一假设。具体目的4是验证Nkx2.2与Nkx6.2共同调节动物生命后期少突胶质细胞髓鞘形成的假设。 这些研究结果将大大加深我们对控制少突胶质细胞早期特化和分化的遗传回路的理解,并可能为设计预防和治疗运动神经元和少突胶质细胞萎缩的新的治疗方法提供理论依据。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Mengsheng Qiu其他文献

Mengsheng Qiu的其他文献

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{{ truncateString('Mengsheng Qiu', 18)}}的其他基金

Molecular regulation of myelin development and repair by Ick kinase
Ick 激酶对髓磷脂发育和修复的分子调节
  • 批准号:
    9237980
  • 财政年份:
    2016
  • 资助金额:
    $ 30.59万
  • 项目类别:
Role of Olig3 in cerebellar and precerebellar development
Olig3 在小脑和小脑前发育中的作用
  • 批准号:
    7522576
  • 财政年份:
    2008
  • 资助金额:
    $ 30.59万
  • 项目类别:
Role of Olig3 gene in gliogenesis
Olig3基因在胶质细胞生成中的作用
  • 批准号:
    6891790
  • 财政年份:
    2004
  • 资助金额:
    $ 30.59万
  • 项目类别:
Role of Olig3 gene in gliogenesis
Olig3基因在胶质细胞生成中的作用
  • 批准号:
    6819070
  • 财政年份:
    2004
  • 资助金额:
    $ 30.59万
  • 项目类别:
Transcriptional control of oligodendrocyte differentiation and myelination
少突胶质细胞分化和髓鞘形成的转录控制
  • 批准号:
    8535829
  • 财政年份:
    2000
  • 资助金额:
    $ 30.59万
  • 项目类别:
Molecular/genetic control of oligodendrocyte development
少突胶质细胞发育的分子/遗传控制
  • 批准号:
    7062446
  • 财政年份:
    2000
  • 资助金额:
    $ 30.59万
  • 项目类别:
Transcriptional control of oligodendrocyte differentiation and myelination
少突胶质细胞分化和髓鞘形成的转录控制
  • 批准号:
    8306874
  • 财政年份:
    2000
  • 资助金额:
    $ 30.59万
  • 项目类别:
MOLECULAR GENETIC CONTROL OF OLIGODENDROCYTE DEVELOPMENT
少突胶质细胞发育的分子遗传控制
  • 批准号:
    6637679
  • 财政年份:
    2000
  • 资助金额:
    $ 30.59万
  • 项目类别:
Transcriptional control of oligodendrocyte differentiation and myelination
少突胶质细胞分化和髓鞘形成的转录控制
  • 批准号:
    8113349
  • 财政年份:
    2000
  • 资助金额:
    $ 30.59万
  • 项目类别:
Molecular/genetic control of oligodendrocyte development
少突胶质细胞发育的分子/遗传控制
  • 批准号:
    7225556
  • 财政年份:
    2000
  • 资助金额:
    $ 30.59万
  • 项目类别:

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