Cytoskeletal mechanisms of dendrite arbor shape development

树突乔木形状发育的细胞骨架机制

基本信息

  • 批准号:
    10649463
  • 负责人:
  • 金额:
    $ 30.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-15 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Abstract The specification and dynamic modification of subtype specific dendritic architecture not only dictates how distinct classes of neurons form functional connections with other neurons, but also directly influences subtype- specific computational properties. Dendritic form, and by extension function, is chiefly mediated by subcellular organization and dynamics of cytoskeletal components. Thus, identifying molecular factors and cellular processes that regulate subtype specific dendritogenesis is essential to our understanding of the mechanistic links between cytoskeletal organization and neuronal form and function in both health and neuropathologies. Protein homeostasis, or proteostasis, is essential to cellular health and as a surveillance system against neurotoxic aggregates implicated in numerous neurodegenerative disease states. Despite this importance, relatively little is known regarding the normal developmental roles of proteostasis regulatory pathways in driving dendritic diversity or subtype-specific cytoskeletal organization. Our work in the previous funding cycle provided the foundations for combining neurogenetic manipulations, in vivo spatio-temporal multichannel imaging and computational techniques for multichannel and time-varying neuronal reconstructions of subtype specific dendritic cytoskeletal architectures. This strategy yielded novel insights into local cytoskeletal control mechanisms regulating dendritic arbor diversity that could not have been solely predicted or quantitatively characterized without the synergy of these approaches. For this next funding cycle, we hypothesize that the evolutionarily conserved PP2A phosphatase and TRiC/CCT chaperonin complexes function as essential proteostasis regulators that exert control over the spatiotemporal organization and dynamics of cytoskeletal components underlying subtype-specific dendritic arbor diversity. To investigate this core hypothesis, we propose the following tightly linked aims. First, we will elucidate the mechanistic role(s) of the PP2A phosphatase and TRiC/CCT chaperonin complex in directing subtype specific dendritic arborization. Second, we will identify the functional requirements and putative molecular targets of PP2A and TRiC/CCT in regulating subtype specific dendritic cytoskeletal architecture and dynamics. Third, we will conduct computational studies of dendritic morphology and spatio-temporal cytoskeletal distributions that directly integrates and synergizes with the first two aims thereby generating a closed-loop investigational system. These studies will not only reveal novel molecular mechanisms driving cytoskeletal organization and dynamics that functionally contribute to the emergence of diverse dendritic arbors, but also develop and disseminate neuroinformatic tools and data of broad impact to the neuroscience community.
摘要

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Bibliometric analysis of neuroscience publications quantifies the impact of data sharing.
对神经科学出版物的文献计量分析量化了数据共享的影响。
An ontology-based search engine for digital reconstructions of neuronal morphology.
基于本体的搜索引擎,用于神经元形态的数字重建。
  • DOI:
    10.1007/s40708-017-0062-x
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Polavaram,Sridevi;Ascoli,GiorgioA
  • 通讯作者:
    Ascoli,GiorgioA
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GIORGIO A ASCOLI其他文献

GIORGIO A ASCOLI的其他文献

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{{ truncateString('GIORGIO A ASCOLI', 18)}}的其他基金

Long-range neuronal projections: circuit blueprint or stochastic targeting? Rigorous classification of brain-wide axonal reconstructions
远程神经元投射:电路蓝图还是随机目标?
  • 批准号:
    10360723
  • 财政年份:
    2021
  • 资助金额:
    $ 30.13万
  • 项目类别:
Anatomical characterization of neuronal cell types of the mouse brain
小鼠大脑神经元细胞类型的解剖学特征
  • 批准号:
    10262970
  • 财政年份:
    2020
  • 资助金额:
    $ 30.13万
  • 项目类别:
Anatomical characterization of neuronal cell types of the mouse brain
小鼠大脑神经元细胞类型的解剖学特征
  • 批准号:
    10225863
  • 财政年份:
    2020
  • 资助金额:
    $ 30.13万
  • 项目类别:
Anatomical characterization of neuronal cell types of the mouse brain
小鼠大脑神经元细胞类型的解剖学特征
  • 批准号:
    9567222
  • 财政年份:
    2017
  • 资助金额:
    $ 30.13万
  • 项目类别:
Cytoskeletal mechanisms of dendrite arbor shape development
树突乔木形状发育的细胞骨架机制
  • 批准号:
    10162670
  • 财政年份:
    2013
  • 资助金额:
    $ 30.13万
  • 项目类别:
Cytoskeletal mechanisms of dendrite arbor shape development
树突乔木形状发育的细胞骨架机制
  • 批准号:
    10404546
  • 财政年份:
    2013
  • 资助金额:
    $ 30.13万
  • 项目类别:
Reconstruction and Mapping of Human Brain Vasculature
人脑脉管系统的重建和绘图
  • 批准号:
    7860671
  • 财政年份:
    2009
  • 资助金额:
    $ 30.13万
  • 项目类别:
Neuroinformatics of the Hippocampus: From System-Level to Neuronal Arborizations
海马体的神经信息学:从系统级到神经元树枝化
  • 批准号:
    7532436
  • 财政年份:
    2008
  • 资助金额:
    $ 30.13万
  • 项目类别:
ANATOMICALLY ACCURATE NEURAL NETWORKS: BUILDING A HIPPOCAMPUS
解剖学上精确的神经网络:构建海马体
  • 批准号:
    7369377
  • 财政年份:
    2006
  • 资助金额:
    $ 30.13万
  • 项目类别:
ANATOMICALLY ACCURATE NEURAL NETWORKS: BUILDING A HIPPOCAMPUS
解剖学上精确的神经网络:构建海马体
  • 批准号:
    7182786
  • 财政年份:
    2005
  • 资助金额:
    $ 30.13万
  • 项目类别:

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