Molecular mechanisms that regulate p38 MAPK-dependent neuronal gene expression
调节 p38 MAPK 依赖性神经元基因表达的分子机制
基本信息
- 批准号:9258109
- 负责人:
- 金额:$ 4.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-01 至 2019-11-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAnatomyAutistic DisorderBiological ModelsBrainCaenorhabditis elegansCalmodulinCellsClinicalDataDefectDense Core VesicleDevelopmentDevelopmental BiologyDiseaseEpilepsyExocytosisFunctional disorderGene ExpressionGene Expression ProfileGene Expression RegulationGene TargetingGenesGeneticGenetic ModelsGenetic TranscriptionHomologous GeneImageLinkLoss of HeterozygosityMAPK11 geneMeasurementMeasuresMediatingMental disordersMethodsMitogen-Activated Protein KinasesMolecularMonitorMorphologyMutateMutationNematodaNervous System PhysiologyNervous system structureNeuronal DifferentiationNeuronsNeurophysiology - biologic functionNeurosciencesNeurosecretionPhenotypeProcessPropertyProtein SecretionReporterRoleSchizophreniaSignal PathwaySignal TransductionStudy modelsTestingTimeTranscriptTransgenesbasecell typeclinically relevantexperimental studyfunctional lossfunctional restorationin vivomitogen-activated protein kinase p38molecular markermutantmutation screeningnervous system disorderneural circuitneurodevelopmentoptogeneticsprogramspromoterrelating to nervous systemtranscriptome sequencingvoltage
项目摘要
Project Summary. The nervous system comprises an extraordinary variety of neuronal cell types. A
differentiated neuron type is defined by a unique gene expression pattern that determines its morphology,
connectivity, and function. Deciphering developmental mechanisms that regulate neuronal gene expression is
a major question in developmental biology and is crucial to understanding nervous system function. Better
understanding of these mechanisms will also impact our understanding of neurological and psychiatric
disorders associated with improper neural gene expression, such as autism and schizophrenia. The nematode
C. elegans is an excellent model for the study of gene expression in the developing nervous system. The C.
elegans nervous system comprises diverse neuron types that use conserved factors to regulate gene
expression. Gene expression in many neuron-types can be monitored in vivo using fluorescent reporter
transgenes, which allows the use of powerful genetic methods to discover factors required for neural gene
expression. Such an approach identified the p38 MAP kinase (MAPK), PMK-3, as a factor required for proper
gene expression and differentiation of a pair of C. elegans chemosensory neurons. We have found that
mutations that block neurosecretion and neural excitability restore neural gene expression to p38 MAPK
mutants, suggesting that neural activity antagonistically regulates p38 MAPK-dependent gene expression that
promotes neurodifferentiation. This proposal will determine how neurosecretion and neural activity antagonize
gene expression that defines a specific neuronal fate. Because activity-regulated gene expression is critical for
the development and function of neural circuits, these studies will advance understanding of processes
fundamental to brain function and whose dysfunction has been linked to neurological and psychiatric disorders.
项目总结。神经系统由种类繁多的神经细胞组成。一个
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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Lauren Bayer Horowitz其他文献
Lauren Bayer Horowitz的其他文献
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{{ truncateString('Lauren Bayer Horowitz', 18)}}的其他基金
Death and Destruction: How the Ubiquitin Proteasome System Executes Linker Cell-type Death
死亡与破坏:泛素蛋白酶体系统如何执行连接细胞型死亡
- 批准号:
10464485 - 财政年份:2022
- 资助金额:
$ 4.4万 - 项目类别:
Death and Destruction: How the Ubiquitin Proteasome System Executes Linker Cell-type Death
死亡与破坏:泛素蛋白酶体系统如何执行连接细胞型死亡
- 批准号:
10793327 - 财政年份:2022
- 资助金额:
$ 4.4万 - 项目类别:
Death and Destruction: How the Ubiquitin Proteasome System Executes Linker Cell-type Death
死亡与破坏:泛素蛋白酶体系统如何执行连接细胞型死亡
- 批准号:
10678636 - 财政年份:2022
- 资助金额:
$ 4.4万 - 项目类别:
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