Investigating the role of a conserved serine/threonine kinase, SAX-1, in higher-order dendrite pruning
研究保守丝氨酸/苏氨酸激酶 SAX-1 在高阶树突修剪中的作用
基本信息
- 批准号:10537345
- 负责人:
- 金额:$ 4.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2025-01-30
- 项目状态:未结题
- 来源:
- 关键词:ActinsAdultAfferent NeuronsAllelesBindingBiologicalBiological ModelsBrainCXCL10 geneCaenorhabditis elegansCalcium SignalingCellsCytoskeletal ModelingCytoskeletonDefectDendritesDevelopmentDiapauseDiseaseDorsalDown SyndromeDrosophila genusEnsureEnzymesExposure toFailureGenesGeneticGenetic ScreeningGoalsImageLarvaLeadLightLinkMeasuresMediatingMicrotubulesMolecularMoltingMusNematodaNervous system structureNeuritesNeurodevelopmental DisorderNeuromuscular JunctionNeuronsNuclearPathway interactionsPhosphotransferasesProcessPropertyProtein-Serine-Threonine KinasesProteinsRegulationReportingResearchResearch ProposalsResolutionRoleSerineShapesSignal PathwaySignal TransductionSisterSuggestionSystemTestingThreonineWorkautism spectrum disorderinnovationinsightlabiamutantnervous system developmentnervous system disorderneural circuitnovelprotein protein interactionrecruitreproductive developmentresponsescaffold
项目摘要
PROJECT SUMMARY
Neurite remodeling is a highly conserved process that refines and establishes a mature nervous system. A failure
in neurite remodeling leads to neurological and neurodevelopmental disorders. While developmental dendritic
pruning, a means of neurite remodeling, has been extensively studied, the cell-biological mechanisms that
control pruning remain poorly understood. Specifically, there is a fundamental gap in understanding how neurons
can selectively prune specific dendritic branches while leaving sister branches intact. The long-term goal is to
identify and understand the cell-biological mechanisms that direct branch-specific pruning. The nematode
Caenorhabditis elegans inner labial 2 (IL2) neurons, upon entering a developmental diapause, extend a
stereotypical dendritic arbor that is pruned when development is resumed – leaving primary dendrites intact. The
stereotypic remodeling of IL2 neurons allows experimental access to elucidate the cell-biological mechanisms
that confer selective pruning. The central hypothesis is that SAX-1, an evolutionarily conversed serine/threonine
kinase, functions in a molecular pathway that links calcium signaling to cytoskeletal dynamics in higher-order
dendrite branches to direct selective pruning. The rationale for this proposal is that studying the role SAX-1
during IL2 remodeling will offer a framework to understand how local regulation of the cytoskeleton confers
branch-specific pruning. The central hypothesis will be tested by the following specific aims: 1) determine how
SAX-1 directs pruning of higher-order IL2 dendrite branches; and 2) identify the genetic pathway in which SAX-
1 acts to regulate the cytoskeleton during pruning. The research proposal is innovative because it will 1) be the
first to establish C. elegans as a model system for studying pruning, 2) elucidate a novel role for SAX-1 in
dendritic pruning, and 3) determine how the cytoskeleton is locally regulated during pruning. The proposed
research is significant because elucidating the fundamental cell-biological mechanisms of branch-specific
pruning will significantly advance our understanding of developmental neurite remodeling. This understanding is
a critical to inform us about how neurodevelopmental processes go awry in disorders such as Down Syndrome.
项目摘要
神经突重塑是一个高度保守的过程,完善和建立一个成熟的神经系统。故障
神经突重塑导致神经和神经发育障碍。发育树突状细胞
修剪是神经突重塑的一种手段,已被广泛研究,
控制修剪仍然知之甚少。具体来说,在理解神经元如何
可以选择性地修剪特定的树枝,同时保持姐妹枝完整。长期目标是
识别和理解指导分支特异性修剪的细胞生物学机制。线虫
秀丽隐杆线虫内阴唇2(IL 2)神经元在进入发育滞育后,延长一段时间。
当发育恢复时被修剪的典型的树突乔木-留下完整的初级树突。的
IL-2神经元的刻板重塑允许实验进入阐明细胞生物学机制
赋予选择性修剪。中心假设是SAX-1,一种进化上转化的丝氨酸/苏氨酸,
激酶,在一个分子途径中起作用,该途径将钙信号传导与细胞骨架动力学以更高的顺序联系起来
树枝状分支直接选择性修剪。提出这一建议的理由是,研究SAX-1的作用
在IL 2重塑过程中,将提供一个框架,以了解细胞骨架的局部调节如何赋予
枝特异性修剪中心假设将通过以下具体目标进行检验:1)确定如何
SAX-1指导高级IL 2树突分支的修剪;和2)鉴定其中SAX-1表达的遗传途径。
1在修剪过程中调节细胞骨架。这项研究提案是创新的,因为它将1)是
首先建立C. 2)阐明了SAX-1在植物修剪中的新作用,
树突修剪,和3)确定如何在修剪过程中局部调节细胞骨架。拟议
研究是重要的,因为阐明了分支特异性的基本细胞生物学机制,
修剪将大大推进我们对发育神经突重塑的理解。这种理解是
这是一个关键,它告诉我们神经发育过程是如何在唐氏综合症等疾病中出错的。
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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{{ truncateString('Paola V Figueroa-Delgado', 18)}}的其他基金
Investigating the role of a conserved serine/threonine kinase, SAX-1, in higher-order dendrite pruning
研究保守丝氨酸/苏氨酸激酶 SAX-1 在高阶树突修剪中的作用
- 批准号:
10709511 - 财政年份:2022
- 资助金额:
$ 4.68万 - 项目类别:
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