Project 1 Genetic Networks Establishing Serontonergic Neuronal Idenity
项目 1 建立血清素能神经元身份的遗传网络
基本信息
- 批准号:7677518
- 负责人:
- 金额:$ 23.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-07-01 至 2012-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAllelesAnxietyAreaBehaviorBehavioralBioinformaticsCharacteristicsCircadian RhythmsCollaborationsDatabasesDevelopmentDiseaseEmbryoEmotionalFlow CytometryFoundationsFutureGene ExpressionGene Expression ProfileGenesGeneticGenetic VariationGlucocorticoid ReceptorGoalsHPSE geneIceImmunohistochemistryIn Situ HybridizationKnock-outKnockout MiceLabelMental disordersMethodologyMolecular GeneticsMolecular ProfilingMoodsMusNeurodevelopmental DisorderNeurologicNeuronsNumbersPainPathogenesisPatternPerceptionPlayPredispositionPreparationProteinsProteomicsRegulationResearchResearch PersonnelResourcesRespirationRiskRisk FactorsRoleSerotoninSignal TransductionSleepStagingStressSystemTamoxifenTestingTimeTransgenic OrganismsVariantaxon growthaxonal guidancebasebiological adaptation to stressclinically relevantenergy balancefollow-upgene functiongenetic varianthypothalamic-pituitary-adrenal axisnerve supplynervous system disorderneurochemistrypostnatalprogramsreceptor functionrecombinasespatiotemporalsynaptogenesistool
项目摘要
Altered 5HT signaling has been implicated in the pathogenesis of numerous neurological and
psychiatric disorders. Many of these disorders are neurodevelopmental in origin and risk for acquiring them
is likely to be influenced by multiple heritable susceptibility factors. In Project 1: Genetic Networks
Establishing Serotonergic Neuronal Identity, Evan Deneris hypothesizes that some of these susceptibility
factors may be allelic variants of genes that govern 5HT neuron development and that these alleles may
contribute to behavioral pathogenesis by adversely increasing or decreasing 5HT system activity. Although
some SERT variants are identifiable risk factors for mental health disorders, the majority of genes involved in
5HT neuron development have not yet been investigated for the presence of disease-associated alleles.
Advances in this area have not been made because 5HT neurons are difficult to access for molecular
genetic studies. Consequently, only a small number of genes that compose the 5HT neuron developmental
program have been identified. An additional critical factor that has hindered progress is that diverse
methodology and expertise is required to investigate the function of 5HT neuron developmental control
genes. Deneris has developed transgenic-based tools that enable direct and highly specific access to
embryonic and adult 5HT neurons. The research proposed here will take advantage of these tools to
interrogate the 5HT neuron transcriptome and thereby identify genes that may control 5HT neuron
development and function. His proposed aims will address the following questions: What network of genes
is expressed during critical stages of embryonic and postnatal 5HT neuron development? What are the
differences between the rostral and caudal 5HT neuron expressed gene networks? Are different stages of
5HT neuron development marked by expression of certain sets of genes? What role does the glucocorticoid
receptor (GR) play in embryonic and adult 5HT neurons? Deneris expects to identify a diverse network of
fTa3ctors that govern different facets of 5HT neuron development and function. Integration of this research into
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orchestrated collaborations with P. Levitt (Project 2), R. Blakely (Project 3), E. Sanders-Bush (Project 4), D.
McMahon (Project 6) and the three Conte Center Cores. Deneris' transgenic lines will provide new tools to
facilitate studies proposed in Projects 2-4 and 6. Project 1's transcriptome databases will provide critical
reference information for studies of mouse 5HT neuron transcriptome function and regulation proposed in
Projects 2-6. Project 1 studies will enable future screens for disease relevant genetic variants in validated
5HT neuron developmental control genes.
改变的5 HT信号传导已经涉及许多神经系统疾病的发病机制,
精神疾病这些疾病中的许多是神经发育的起源和风险,为获得他们
可能受多种遗传易感因素的影响。项目1:基因网络
在建立5-羟色胺能神经元身份的基础上,Evan Deneris假设这些易感性中的一些可能是由于
因子可能是控制5 HT神经元发育的基因的等位基因变体,并且这些等位基因可能
通过不利地增加或减少5-HT系统活性而导致行为发病机制。虽然
一些SERT变异是精神健康障碍的可识别风险因素,大多数基因涉及
尚未研究5 HT神经元发育是否存在疾病相关等位基因。
在这一领域尚未取得进展,因为5 HT神经元难以进入分子水平。
基因研究。因此,只有少数基因组成的5 HT神经元发育,
方案已经确定。阻碍进展的另一个关键因素是,
研究5-HT神经元发育控制的功能需要方法学和专业知识
基因. Deneris开发了基于转基因的工具,可以直接和高度特异性地获得
胚胎和成体5 HT神经元。这里提出的研究将利用这些工具,
询问5 HT神经元转录组,从而鉴定可能控制5 HT神经元的基因
发展和功能。他提出的目标将解决以下问题:
在胚胎和出生后5 HT神经元发育的关键阶段表达?有哪些
头端和尾端5-HT神经元表达基因网络的差异?是不同阶段的
5 HT神经元的发育以某些基因的表达为标志?糖皮质激素的作用是什么
受体(GR)在胚胎和成人5-HT神经元中的作用?Deneris希望确定一个多样化的网络,
控制5-HT神经元发育和功能的不同方面的因子。将这项研究纳入
听着CacotnetreistCicesntoefrcapnrod jiedcatewisllergorteoantelyrgfaicimlitartkeesrstudniedsfuanimcteiodnaltsdtuedteierms ionfinGgRththerosuppagahtioctagermepfuollyalpleaxnpensaiondn
与P. Levitt(项目2),R. Blakely(Project 3),E. Sanders-Bush(Project 4),D.
麦克马洪(项目6)和三个孔蒂中心核心。Deneris的转基因品系将提供新的工具,
促进项目2-4和6中建议的研究。项目1的转录组数据库将提供关键的
研究小鼠5 HT神经元转录组功能和调节的参考信息,
项目2-6。项目1的研究将使未来的筛选疾病相关的遗传变异,
5 HT神经元发育控制基因。
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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EVAN S DENERIS其他文献
EVAN S DENERIS的其他文献
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{{ truncateString('EVAN S DENERIS', 18)}}的其他基金
Gene regulatory mechanisms controlling development of serotonin neuron subtypes
控制血清素神经元亚型发育的基因调控机制
- 批准号:
10363390 - 财政年份:2021
- 资助金额:
$ 23.71万 - 项目类别:
Brain serotonin neuron gene regulatory networks and chromatin architecture
大脑血清素神经元基因调控网络和染色质结构
- 批准号:
10515314 - 财政年份:2019
- 资助金额:
$ 23.71万 - 项目类别:
Brain serotonin neuron gene regulatory networks and chromatin architecture
大脑血清素神经元基因调控网络和染色质结构
- 批准号:
10295748 - 财政年份:2019
- 资助金额:
$ 23.71万 - 项目类别:
Brain serotonin neuron gene regulatory networks and chromatin architecture
大脑血清素神经元基因调控网络和染色质结构
- 批准号:
9858432 - 财政年份:2019
- 资助金额:
$ 23.71万 - 项目类别:
Early Brain Serotonin and Its Lasting Impact on Neuronal Epigenetic Programming
早期大脑血清素及其对神经元表观遗传编程的持久影响
- 批准号:
8441969 - 财政年份:2012
- 资助金额:
$ 23.71万 - 项目类别:
Project 1 Genetic Networks Establishing Serontonergic Neuronal Idenity
项目 1 建立血清素能神经元身份的遗传网络
- 批准号:
8134923 - 财政年份:2010
- 资助金额:
$ 23.71万 - 项目类别:
Project 1 Genetic Networks Establishing Serontonergic Neuronal Idenity
项目 1 建立血清素能神经元身份的遗传网络
- 批准号:
7921653 - 财政年份:2009
- 资助金额:
$ 23.71万 - 项目类别:
Project 1 Genetic Networks Establishing Serontonergic Neuronal Idenity
项目 1 建立血清素能神经元身份的遗传网络
- 批准号:
7305758 - 财政年份:2007
- 资助金额:
$ 23.71万 - 项目类别:
PET 1 ETS FACTOR IN THE MAMMALIAN 5 HT SYSTEM
哺乳动物 5 HT 系统中的 PET 1 ETS 因子
- 批准号:
6825754 - 财政年份:2000
- 资助金额:
$ 23.71万 - 项目类别:
PET 1 ETS FACTOR IN THE MAMMALIAN 5 HT SYSTEM
哺乳动物 5 HT 系统中的 PET 1 ETS 因子
- 批准号:
6259519 - 财政年份:2000
- 资助金额:
$ 23.71万 - 项目类别:
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