GABAergic Neuron Differentiation in C.elegans
线虫中 GABA 能神经元的分化
基本信息
- 批准号:10442930
- 负责人:
- 金额:$ 4.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-15 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AnabolismAxonCaenorhabditis elegansComplexDNA Sequence AlterationDevelopmentDissectionEmbryoEnsureGeneticHumanKnowledgeLightLinkMaintenanceMediatingMicrotubulesMolecular GeneticsMorphologyMotorMotor NeuronsNervous system structureNeuronsOrganismPathway interactionsPatternPhospholipidsPhosphotransferasesPhysiologicalPlayProteinsResolutionRoleSignal TransductionSpecificityStereotypingStimulusSynapsesSystemTertiary Protein StructureTissuesTransmembrane DomainVisualizationcholinergiccholinergic neuronhuman diseasein vivoin vivo imaginginnovative technologiesinsightnervous system disorderneuronal circuitrynoveloperationsrc-Family Kinasessynaptic functionsynaptogenesis
项目摘要
Throughout a lifetime of an organism synapse addition and elimination is on-going to ensure proper
function of neuronal circuits. Growing evidence have revealed complex interactions involving intrinsic
and extrinsic factors in synapse refinement with temporal and neuronal-type specificity. Studies using C.
elegans have continued to expand the understanding of molecular and genetic pathways with single-
synapse resolution. The locomotor circuit consists of several classes of excitatory cholinergic motor
neurons and two classes of GABAergic motor neurons, and is a highly tractable system to discover
mechanisms underlying synapse formation and refinement. Each neuron forms stereotyped pattern and
number of synapses, providing an accurate readout to examine how synapses are dynamically regulated.
Moreover, the development of the mature locomotor circuit involves a precisely timed remodeling of the
embryonically born GABAergic neurons, known as “DD synapse remodeling”, in the absence of axonal
morphological changes. We developed the first in vivo visualization approach to examine DD synapse
remodeling. In our recent studies, we have defined critical roles of microtubule dynamics in promoting
cargo and motor interaction in the formation of new synapses in DD remodeling. Our findings underscore
the concept that microtubules are not passive tracks but play an active role in cellular signaling. In the
specific Aim 1 of this renewal application we will leverage our expertise in genetic pathway dissection
with in vivo imaging of microtubule components to dissect the roles of a novel kinase in DD synapse
remodeling. In parallel, we have investigated the mechanisms regulating the cholinergic neuron
synapses, and have uncovered roles of inter-tissue interaction mediated by a IgSF transmembrane
domain protein ZIG-10. Our studies show that ZIG-10 regulates phagocytotic pathway via a SRC kinase
in the adjacent non-neuronal tissues. In specific Aim 2, we will tackle the cellular action and the
physiological impact of this pathway using innovative technologies. We will further examine how neuronal
activity regulates this pathway. In Aim 3, we will investigate the role of a conserved MAGUK protein that
may link the ZIG-10 pathway to phospholipid biosynthesis in synapse maintenance. Genetic mutations
of homologous molecules in human have been linked to various neurological diseases. Together our
findings will provide important insights to the underlying signaling network and advance our knowledge
in the understanding of human diseases.
在整个生物体的一生中,突触的增加和消除是持续进行的,以确保适当
项目成果
期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Intragenic suppressors of unc-104 ( e1265 ) identify potential roles of the conserved stalk region.
- DOI:10.17912/micropub.biology.000539
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Byrd, Dana T;Pearlman, Julie M;Jin, Yishi
- 通讯作者:Jin, Yishi
Microtubule-dependent ribosome localization in C. elegans neurons.
- DOI:10.7554/elife.26376
- 发表时间:2017-08-02
- 期刊:
- 影响因子:7.7
- 作者:Noma K;Goncharov A;Ellisman MH;Jin Y
- 通讯作者:Jin Y
Wired for insight-recent advances in Caenorhabditis elegans neural circuits.
- DOI:10.1016/j.conb.2021.02.009
- 发表时间:2021-08
- 期刊:
- 影响因子:5.7
- 作者:Byrd DT;Jin Y
- 通讯作者:Jin Y
An intraflagellar transport dependent negative feedback regulates the MAPKKK DLK-1 to protect cilia from degeneration.
- DOI:10.1073/pnas.2302801120
- 发表时间:2023-09-26
- 期刊:
- 影响因子:11.1
- 作者:Sun, Yue;Jin, Yishi
- 通讯作者:Jin, Yishi
Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17.
- DOI:10.1016/j.celrep.2020.108365
- 发表时间:2020-11-17
- 期刊:
- 影响因子:8.8
- 作者:Niu J;Sanders SS;Jeong HK;Holland SM;Sun Y;Collura KM;Hernandez LM;Huang H;Hayden MR;Smith GM;Hu Y;Jin Y;Thomas GM
- 通讯作者:Thomas GM
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Yishi Jin其他文献
Yishi Jin的其他文献
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{{ truncateString('Yishi Jin', 18)}}的其他基金
2023 Central Nervous System Injury and Repair Gordon Research Conference and Seminar
2023中枢神经系统损伤与修复戈登研究会议暨研讨会
- 批准号:
10753737 - 财政年份:2023
- 资助金额:
$ 4.08万 - 项目类别:
Molecular genetics of axon and synapse development and maintenance
轴突和突触发育和维持的分子遗传学
- 批准号:
10610882 - 财政年份:2022
- 资助金额:
$ 4.08万 - 项目类别:
Molecular genetics of axon and synapse development and maintenance
轴突和突触发育和维持的分子遗传学
- 批准号:
10456448 - 财政年份:2022
- 资助金额:
$ 4.08万 - 项目类别:
ORGANIZATION OF PRESYNAPTIC ACTIVE ZONE BASED ON TOMOGRAPHIC RECONSTRUCTION
基于断层重建的突触前活动区组织
- 批准号:
8169634 - 财政年份:2010
- 资助金额:
$ 4.08万 - 项目类别:
ORGANIZATION OF PRESYNAPTIC ACTIVE ZONE BASED ON TOMOGRAPHIC RECONSTRUCTION
基于断层重建的突触前活动区组织
- 批准号:
7957647 - 财政年份:2009
- 资助金额:
$ 4.08万 - 项目类别:
ORGANIZATION OF PRESYNAPTIC ACTIVE ZONE BASED ON TOMOGRAPHIC RECONSTRUCTION
基于断层重建的突触前活动区组织
- 批准号:
7722482 - 财政年份:2008
- 资助金额:
$ 4.08万 - 项目类别:
GABAergic Neuron Differentiation in C. elegans
线虫中的 GABA 能神经元分化
- 批准号:
6949633 - 财政年份:1996
- 资助金额:
$ 4.08万 - 项目类别:
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