Coordination of projection neuron fate and position by let-7
let-7 协调投射神经元的命运和位置
基本信息
- 批准号:10722629
- 负责人:
- 金额:$ 42.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AffectApicalBehaviorBiologicalBiosensorCell CycleCellsCentral Nervous SystemCognition DisordersCompetenceConserved SequenceCore ProteinDataDate of birthDefectDevelopmentDevelopmental BiologyEmbryonic DevelopmentEnvironmentFailureImageImaging TechniquesKnowledgeLeadLinkLocationMass Spectrum AnalysisMicroRNAsModelingMolecularMolecular Mechanisms of ActionNeocortexNeurogliaNeurologicNeuronsPatternPopulationPopulation ProjectionPositioning AttributeProcessPsyche structureRadialResearchRoleSideSignal TransductionSurfaceTestingTransplantationbrain malformationcell typecohortlateral ventriclemembermigrationmultipotent cellneocorticalnerve stem cellneuralneurogenesisnoveloverexpressionpostmitoticprogenitorresponseubiquitin-protein ligase
项目摘要
Project Summary:
The central nervous system contains a myriad of different cell types that receive and integrate information from
the environment to generate the appropriate biological responses. Failure to produce the right composition of
neuronal subtypes or defects in their localization can result in several mental and physical conditions that range
from cognitive disorders to severe brain malformations. In the neocortex, a specialized pool of multipotent cells
-called radial glial cells- gives rise to all the different populations of projection neurons in a conserved sequence.
Importantly, early born projections neurons localize at the apical side of the cortical plate whereas later born
neurons localize atop of their predecessors. Despite the strong correlation between projection neuron fate
identity and position, the molecular mechanisms involved in such correlation remain elusive. MicroRNAs
(miRNAs) have recently been uncovered as strong cell fate determinants and we and others have shown that
let-7 expression in radial glia cells promotes the neurogenesis of late born cortical projection neurons.
Importantly, we further demonstrate that let-7 expression positive correlates with projection neuron location in
upper cortical layers (i.e., closer to the pial surface). Our preliminary data show that let-7 regulates neuron
migration by opposing the expression of Rbx2, a core member of the E3 ubiquitin ligase CRL5, previously
identified as a key factor to end projection neuron migration. Thus, we hypothesize that elevated expression of
let-7 in late-born projection neurons reduces the activity of CRL5, promoting neuron migration. The proposed
research will identify let-7 as the first coordinator of neural progenitor competence and projection neuron
migration/localization, and unveil its molecular mechanism of action.
项目概要:
中枢神经系统包含无数不同的细胞类型,它们接收和整合来自
环境产生适当的生物反应。未能产生正确的成分,
神经元亚型或其定位缺陷可导致多种精神和身体状况,
从认知障碍到严重的脑畸形在大脑新皮层中,有一个专门的多能细胞池
放射状神经胶质细胞以保守的顺序产生所有不同的投射神经元。
重要的是,早期出生的投射神经元位于皮质板的顶侧,而晚出生的投射神经元位于皮质板的顶侧。
神经元位于它们的前辈之上。尽管投射神经元的命运与
身份和位置,参与这种相关性的分子机制仍然难以捉摸。微rna
最近发现,miRNAs是强有力的细胞命运决定因子,我们和其他人已经证明,
放射状胶质细胞中let-7的表达促进晚生皮质投射神经元的神经发生。
重要的是,我们进一步证明let-7表达与投射神经元的位置相关,
上皮质层(即,更接近软膜表面)。我们的初步数据表明let-7调节神经元
通过对抗Rbx2的表达,Rbx2是E3泛素连接酶CRL 5的核心成员,
被认为是结束投射神经元迁移的关键因素。因此,我们假设,
晚期投射神经元中的let-7降低了CRL 5的活性,促进了神经元迁移。拟议
研究将确定let-7是神经祖细胞能力和投射神经元的第一个协调者。
迁移/定位,并揭示其分子作用机制。
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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Anna La Torre其他文献
Anna La Torre的其他文献
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{{ truncateString('Anna La Torre', 18)}}的其他基金
Embryonic Stem Cell Approach to Retinal Ganglion Cell Replacement: an In Vivo Study
胚胎干细胞替代视网膜神经节细胞的方法:体内研究
- 批准号:
9319272 - 财政年份:2016
- 资助金额:
$ 42.24万 - 项目类别:
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