Mechanisms of neural circuit formation in C. elegans
线虫神经回路形成机制
基本信息
- 批准号:9003418
- 负责人:
- 金额:$ 29.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-30 至 2020-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAnimal ModelApoptosisApoptoticAutistic DisorderAxonBirthBrainCaenorhabditis elegansCalcium SignalingCaspaseCell DeathCellsClinical ResearchDataDefectDendritesDevelopmentDiseaseDissectionDorsalDown SyndromeDrug TargetingElectron MicroscopyElectrophysiology (science)Fragile X SyndromeFunctional disorderFutureGap JunctionsGenerationsGeneticHead MovementsIndividualKnowledgeLeadLeftMicrofilamentsMicrotubulesMitochondriaModelingMolecularMotor NeuronsMuscleNervous system structureNeuritesNeurodegenerative DisordersNeurodevelopmental DisorderNeurogliaNeuronsOutcomePathway interactionsPhysiologicalPlayPrader-Willi SyndromeProcessProteinsRegulationRoleSignal TransductionSpecific qualifier valueSynapsesSynaptic plasticitySystemTimeTransgenic OrganismsWorkaxon growthaxon regenerationbasechronic painexperiencegenetic analysisin vivoin vivo imaginginjury and repairinnovationmigrationneural circuitneurodevelopmentneuron developmentneuronal circuitrynovelpublic health relevancerelating to nervous systemsynaptogenesistool
项目摘要
DESCRIPTION (provided by applicant): Neural circuit formation is a critical step of brain development, and disruption of neural circuit formation causes many birth conditions. The formation of a functional circuit requires the intricate orchestration of multiple steps, including
fate determination, migration, axon/dendrite differentiation, axon growth, and synapse formation and elimination. However it is still unclear how individual neurons are assembled into the functional circuits during development. Here, we propose to use the development of a defined neuronal circuit in Caenorhabditis elegans-the RME circuit- to study molecular mechanisms of neural circuit formation. RME circuit development utilizes all the critical steps of mammalian cortex development and involves neuron- neuron, neuron-glia, and neuron-muscle interactions. This system has enabled us to analyze neural circuit formation from the birth of neurons to the maturation of functional circuits. In this proposal we focus on address two important questions: how do glial cells instruct neuronal polarity through gap junctions, and what is the local regulatory mechanism of the cell death pathway in synapse elimination. In our preliminary studies we uncovered a previous unknown function of glial cells during neuronal development in which glial cells form gap junctions with nearby neurons to regulate microtubule polarity and neuronal polarity. We propose studies of the molecular mechanism underlying this observation. The final step of the circuit formation is refinement of synaptic connections through synapse elimination. We found that local activation of the cell death pathway is required for synapse elimination, and this local activation needs the presence of mitochondria. In this application we outline a strategy to address the long time questions in the field: how the apoptotic pathway is locally activated without causing cell death, and what are the downstream targets of caspases in neuronal development. Completion of this proposal will lead to the discovery of novel mechanisms of neural circuit formation, establish the development of RME circuit as a powerful model to study neural circuit formation, and generate new tools for further studies. Given that many neural disorders are associated with defects in neural circuit formation, it is hopeful that this project will help to understand brain development under both physiological and pathological conditions.
描述(由申请人提供):神经回路形成是大脑发育的关键步骤,神经回路形成的破坏会导致许多出生条件。功能电路的形成需要多个步骤的复杂编排,包括
命运决定、迁移、轴突/树突分化、轴突生长和突触形成和消除。然而,目前还不清楚单个神经元在发育过程中是如何组装成功能回路的。在这里,我们建议使用一个定义的神经元回路在秀丽隐杆线虫的RME电路的发展,研究神经回路形成的分子机制。RME回路的发育利用了哺乳动物皮层发育的所有关键步骤,并涉及神经元-神经元、神经元-神经胶质和神经元-肌肉相互作用。该系统使我们能够分析从神经元诞生到功能回路成熟的神经回路形成。在本研究中,我们着重于解决两个重要问题:胶质细胞如何通过缝隙连接来指导神经元的极性,以及突触消除中细胞死亡途径的局部调节机制是什么。在我们的初步研究中,我们发现了神经胶质细胞在神经元发育过程中的一个先前未知的功能,其中神经胶质细胞与附近的神经元形成间隙连接,以调节微管极性和神经元极性。我们建议研究这一观察的分子机制。回路形成的最后一步是通过消除突触来细化突触连接。我们发现,突触消除需要细胞死亡途径的局部激活,而这种局部激活需要线粒体的存在。在本申请中,我们概述了一种策略,以解决该领域的长期问题:如何在不引起细胞死亡的情况下局部激活凋亡途径,以及在神经元发育中半胱天冬酶的下游靶点是什么。这一提议的完成将导致发现新的神经回路形成机制,建立RME回路的发展作为一个强大的模型来研究神经回路的形成,并产生新的工具,为进一步的研究。鉴于许多神经系统疾病与神经回路形成缺陷有关,希望该项目将有助于了解生理和病理条件下的大脑发育。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Dong Yan其他文献
Dong Yan的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Dong Yan', 18)}}的其他基金
Use of C. elegans as a model to study aging-associated neurodegeneration
使用秀丽隐杆线虫作为模型来研究与衰老相关的神经变性
- 批准号:
10444175 - 财政年份:2022
- 资助金额:
$ 29.56万 - 项目类别:
Use of C. elegans as a model to study aging-associated neurodegeneration
使用秀丽隐杆线虫作为模型来研究与衰老相关的神经变性
- 批准号:
10624422 - 财政年份:2022
- 资助金额:
$ 29.56万 - 项目类别:
Use of C. elegans as a model to study aging-associated neurodegeneration
使用秀丽隐杆线虫作为模型来研究与衰老相关的神经变性
- 批准号:
10452825 - 财政年份:2021
- 资助金额:
$ 29.56万 - 项目类别:
Genetic study of gap junction formation and regulation in C. elegans neurons
秀丽隐杆线虫神经元间隙连接形成和调节的遗传学研究
- 批准号:
10426307 - 财政年份:2018
- 资助金额:
$ 29.56万 - 项目类别:
Genetic study of gap junction formation and regulation in C. elegans neurons
秀丽隐杆线虫神经元间隙连接形成和调节的遗传学研究
- 批准号:
10187665 - 财政年份:2018
- 资助金额:
$ 29.56万 - 项目类别:
Genetic study of gap junction formation and regulation in C. elegans neurons
秀丽隐杆线虫神经元间隙连接形成和调节的遗传学研究
- 批准号:
9792289 - 财政年份:2018
- 资助金额:
$ 29.56万 - 项目类别:
Mechanisms of neural circuit formation in C. elegans
线虫神经回路形成机制
- 批准号:
9768244 - 财政年份:2015
- 资助金额:
$ 29.56万 - 项目类别:
Mechanisms of neural circuit formation in C. elegans
线虫神经回路形成机制
- 批准号:
9557592 - 财政年份:2015
- 资助金额:
$ 29.56万 - 项目类别:
Mechanisms of neural circuit formation in C. elegans
线虫神经回路形成机制
- 批准号:
9346674 - 财政年份:2015
- 资助金额:
$ 29.56万 - 项目类别:
Regulation of the DLK-1 pathway in axon regeneration
DLK-1 通路在轴突再生中的调节
- 批准号:
8802904 - 财政年份:2011
- 资助金额:
$ 29.56万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 29.56万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 29.56万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 29.56万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 29.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 29.56万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 29.56万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 29.56万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 29.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 29.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 29.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)