Met Signaling in Neural Development and Circuitry Formation
Met Signaling in Neural Development and Circuitry Formation
批准号:
8627207
负责人:
Shenfeng Qiu
金额:
$23.86万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-02-10 至 2016-02-29
关键词:
7q31AblationAllelesAnimal ModelAnxietyAutistic DisorderAwardBehaviorBehavioralBrainCaliforniaCommitDendritic SpinesDevelopmentDevelopment PlansDorsalEtiologyFamilyForebrain DevelopmentFunctional disorderFutureGene ExpressionGeneticGenetic TranscriptionGlutamatesGoalsGrowthHepatocyte Growth FactorHippocampus (Brain)HumanHuman ChromosomesHuman GeneticsIn VitroInstitutesInterneuronsInterventionKnockout MiceLasersLeadLigandsMET geneMapsMediatingMental disordersMentorsMolecularMonomeric GTP-Binding ProteinsMorphogenesisMorphologyMusNeurobiologyNeurodevelopmental DisorderNeuronsNeurosciences ResearchNucleic Acid Regulatory SequencesOrganPathway interactionsPatientsPlayPrefrontal CortexProcessProsencephalonReceptor Protein-Tyrosine KinasesRelative RisksResearchRoleScanningScientistSeizuresSignal TransductionSocial InteractionStagingSymptomsSynapsesSynaptic plasticitySyndromeSystemTestingUniversitiesVariantWorkautism spectrum disorderbasecareercareer developmentcell typecohortcritical developmental periodgenome wide association studyin vivoinformation processinginsightmedical schoolsmeetingsmembermigrationneural circuitneurite growthneurodevelopmentneurogenesisneurogeneticsneuron developmentneuronal growthnovelresearch studyrhorisk variantsignal processingsynaptic functionsynaptogenesistooltranslational neuroscience
中文摘要
项目概要
这个拟议的独立之路奖描述了一个五年职业发展计划,导致
独立的学术研究。申请人是一位致力于博士后研究工作的科学家
过去四年半在范德比尔特大学神经生物学领域工作。 2009年7月,他将带着他的
南方大学凯克医学院 Zilkha 神经遗传学研究所导师 Pat Levitt
加利福尼亚州,这项拟议工作将在那里进行。本研究的长期目标是
了解 Met 受体酪氨酸激酶在神经发育和电路形成中的作用。蛋氨酸
其配体肝细胞生长因子的激活在多个器官的个体发生中发挥多效性作用。在
在发育中的前脑中,Met 表达受到暂时调节,并在广泛发育时期达到峰值
神经元生长和突触形成。我们实验室和其他实验室最近进行的人类遗传学研究
确定 MET 是自闭症谱系障碍的风险基因,自闭症谱系障碍是一种主要的神经发育综合征,
扰乱神经元活动和连接。然而,Met 在突触功能和微电路中的作用
目前组装情况未知。提出了三个具体目标:1)研究 Met 信号传导在
海马体的发育和功能。发育过程中形态和功能的改变
海马体将由于 Met 信号传导的改变(过度表达、敲低和
有条件的基因删除); 2) 确定调节Met诱导的神经元生长的分子机制
和海马神经元发育中的突触发生。尤其是Rho家族成员的作用
将研究小型 GTPases; 3)探索局部前额皮质突触回路的潜在改变
前脑条件性 Met 缺失所致。这些研究非常重要且高度相关,因为它们
提供关于前脑发育中 Met 介导的分子、细胞和信号传导的机制见解
系统级别。从这项研究中获得的观点将帮助申请人建立研究独立性和
为实现他在转化神经科学研究方面的长期职业目标奠定了科学基础。
英文摘要
Project summary
This proposed Pathway to Independence award describes a five-year career development plan leading to
independent academic research. The applicant is a committed scientist conducting postdoctoral research work
in the field of Neurobiology at Vanderbilt for the past four and half years. In July, 2009, he will move with his
mentor, Pat Levitt, to the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern
California, where this proposed work will be carried out. The long-term objective of this proposed research aims
at understanding the role of the Met receptor tyrosine kinase in neural development and circuitry formation. Met
activation by its ligand, hepatocyte growth factor, plays a pleiotropic role in the ontogenesis of multiple organs. In
the developing forebrain, Met expression is temporally regulated and peaks during the period of extensive
neuronal growth and synapse formation. Recent human genetic studies conducted in our lab and others have
identified MET as a risk gene for autism spectrum disorder, a major neurodevelopmental syndrome with
disrupted neuronal activity and connectivity. However, the role of Met in synapse function and microcircuit
assembly is currently unknown. Three specific aims are proposed: 1) to investigate role of Met signaling in the
development and function of the hippocampus. Both morphological and functional alterations in the developing
hippocampus will be determined as a result of altered Met signaling (over-expression, knockdown and
conditional genetic deletion); 2) to determine molecular mechanisms regulating Met-induced neuronal growth
and synaptogenisis in developing hippocampal neurons. In particular, the role of the members of Rho family
small GTPases will be studied; 3) to explore potential alterations in the local prefrontal cortex synaptic circuitry
resulted from forebrain conditional Met deletion. These studies are important and highly relevant in that they
provide mechanistic insights on Met-mediated signaling in forebrain development at molecular, cellular and
system levels. Perspectives gained from this study will help the applicant establish research independence and
form the scientific basis for achieving his long-term career goals in translational neuroscience research.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
Rescue of synaptic pathology in an Alzheimer's mouse model by enhancing MET receptor tyrosine kinase signaling
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批准号:10507127
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项目类别:
-
资助金额:$42.21万
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财政年份:2022
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负责人:Shenfeng Qiu
-
依托单位:
MET receptor tyrosine kinase and the development of forebrain circuits
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批准号:9913595
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项目类别:
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资助金额:$38.38万
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财政年份:2017
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负责人:Shenfeng Qiu
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依托单位:
Met Signaling in Neural Development and Circuitry Formation
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批准号:8419407
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项目类别:
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资助金额:$24.9万
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财政年份:2010
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负责人:Shenfeng Qiu
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依托单位:
Met Signaling in Neural Development and Circuitry Formation
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批准号:8026022
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项目类别:
-
资助金额:$8.38万
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财政年份:2010
-
负责人:Shenfeng Qiu
-
依托单位:
Met Signaling in Neural Development and Circuitry Formation
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批准号:7770639
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项目类别:
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资助金额:$8.2万
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财政年份:2010
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负责人:Shenfeng Qiu
-
依托单位:
Met Signaling in Neural Development and Circuitry Formation
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批准号:8429488
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项目类别:
-
资助金额:$23.0万
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财政年份:2010
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负责人:Shenfeng Qiu
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依托单位:
海外基金