Linking neuronal identity transcription factors to neural circuit establishment and maintenance
将神经元身份转录因子与神经回路的建立和维护联系起来
基本信息
- 批准号:10386149
- 负责人:
- 金额:$ 6.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAffectAgingAttention deficit hyperactivity disorderAxonBiological AssayBiological MetamorphosisBrainCaenorhabditis elegansCell surfaceCognitionComplexCoupledDataDefectDendritesDevelopmentDevelopmental ProcessDrosophila genusDrug abuseEmbryoEsthesiaEventFoundationsGene ExpressionGilles de la Tourette syndromeGoalsHormonesIndividualInterneuronsLarvaLeadLearningLifeLinkLocomotionMaintenanceMammalsMembraneMental disordersModelingMolecularMolecular ProfilingMorphologyMotorMovementNeuraxisNeuritesNeurodevelopmental DisorderNeuronal PlasticityNeuronsNeurotransmittersOutcomePhenotypePropertyPubertyRNA interference screenRiskRoleSchizophreniaShapesSleepSpecific qualifier valueSynapsesSystemTestingTherapeuticWalkingWorkautism spectrum disorderbehavioral phenotypingexperimental studyflyhomeodomaininterestmolecular markerneural circuitneural patterningneurogenesisneuromechanismoptogeneticsrelating to nervous systemresponsetranscription factor
项目摘要
PROJECT SUMMARY/ABSTRACT
Neuronal identity is generated during development, with identity characterized by neuron-specific
gene expression, axon/dendrite morphology, and connectivity. Homeodomain transcription factors
(TFs) are required for establishing gene expression and neuronal morphology, but whether they are
required for neuronal connectivity is unknown. Understanding the developmental processes
generating neuronal identity in general, and connectivity in particular, is essential for understanding
brain assembly and function. An attractive model is that homeodomain TFs – known to regulate
neuronal molecular and morphological identity – also facilitate the expression of cell surface
molecules that allow the formation of highly-specific neural connections. Connections between
individual neurons contribute to neural circuits, which allow sensation, movement and cognition.
Proper circuit function throughout life relies on continued circuit remodeling, both synaptically and
structurally. Interestingly, homeodomain TFs are expressed in adult neurons, well after neuronal
identity has been established. I hypothesize that the homeodomain TFs are required for neural
circuit establishment and maintenance throughout life. To test this, I have performed a
systematic screen for homeodomain TFs required for the function of a locomotor neural circuit in
Drosophila, the Moonwalker Descending Neuron (MDN) and Pair1 circuit. I have identified 16
homeodomain TFs required for MDN or Pair1 optogenetic induced locomotion. In Aim 1, I will test
how these 16 homeodomain TFs contribute to neuronal identity by assaying molecular identity,
axon/dendrite morphology, and connectivity. My pilot experiments have already shown that the
homeodomain TF Bicoid is required for connectivity but not molecular identity or morphology. In Aim
2, I will utilize how the MDN-Pair1 circuit is remodeled during Drosophila metamorphosis and persists
in the adult fly. I will assay whether the TFs required for establishing MDN-Pair1 connectivity are also
required for maintaining the MDN-Pair1 circuit throughout adulthood. My pilot data shows that Bicoid
is also expressed in the adult Pair1 neurons. My overarching goal is to advance the understanding of
how developmental mechanisms, specifically homeodomain TFs, establish circuits during
development and maintain circuits after periods of plasticity/remodeling. Given that fly and
mammalian neurogenesis share many conserved features, that homeodomain TFs are highly
conserved between species, and that aberrant neural circuits have been implicated in
neurodevelopmental and psychiatric disorders, we expect our results to be both translatable and
therapeutically relevant.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Kristen M Lee其他文献
Measuring context-response associations that drive habits.
衡量推动习惯的情境反应关联。
- DOI:
10.1002/jeab.893 - 发表时间:
2023 - 期刊:
- 影响因子:2.7
- 作者:
J. Labrecque;Kristen M Lee;Wendy Wood - 通讯作者:
Wendy Wood
Glial cell mechanisms regulate alcohol sedation in Drosophila melanogaster
- DOI:
10.25772/vcgf-ne09 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Kristen M Lee - 通讯作者:
Kristen M Lee
A locomotor neural circuit persists and functions similarly in larvae and adult Drosophila
幼虫和成年果蝇的运动神经回路持续存在且功能相似
- DOI:
10.1101/2021.04.27.441684 - 发表时间:
2021 - 期刊:
- 影响因子:7.7
- 作者:
Kristen M Lee;C. Doe - 通讯作者:
C. Doe
Kristen M Lee的其他文献
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{{ truncateString('Kristen M Lee', 18)}}的其他基金
Linking neuronal identity transcription factors to neural circuit establishment and maintenance
将神经元身份转录因子与神经回路的建立和维护联系起来
- 批准号:
10608936 - 财政年份:2022
- 资助金额:
$ 6.98万 - 项目类别:
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