The role of Myt1l in the developing and adult mouse brain
Myt1l 在发育中和成年小鼠大脑中的作用
基本信息
- 批准号:10579921
- 负责人:
- 金额:$ 69.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdultAffectAnxietyBehavior assessmentBehavioralBehavioral AssayBindingBinding ProteinsBiological AssayBiological ModelsBrainBrain regionCategoriesChromatinClassificationCommunicationDataDevelopmentEmbryoEnzymesFamily memberFibroblastsFoundationsFunctional disorderGene Expression RegulationGene FamilyGenesGenetic EpistasisGenetic TranscriptionGenomicsGoalsHeterozygoteIn SituInterventionKnockout MiceLearningLinkMass Spectrum AnalysisMediatingMemoryMolecularMorphologyMotivationMotorMusMutateMutationNeurodevelopmental DisorderNeuronsPathway interactionsPatientsPatternPerformancePhenotypeProbabilityPropertyProteinsPublishingRegulatory PathwayReportingResearchResearch Project GrantsResearch ProposalsRoleSchizophreniaSiteSliceSocial InteractionSortingSynapsesTestingTherapeuticTimeWorkZinc Fingersautism spectrum disorderautistic childrenbehavioral phenotypingexperimental studyfallsfunctional groupgene repressionin vivoinsightknock-downloss of functionmemberneurogenesisneuropsychiatric disorderpharmacologicpostmitoticpostnatalprogramsrecruitsmall hairpin RNAsynaptic functiontranscription factortranscriptomevirtual
项目摘要
We found that the three transcription factors Ascl1, Myt1-like (Myt1l), and Brn2 can reprogram fibroblasts
directly into functional neurons and are thus powerful neuronal lineage determination factors. Ascl1 and Brn2
are well studied genes. Myt1l on the other hand is a fairly uncharacterized zinc finger domain containting
protein predicted to be a transcription factor. It has a remarkably unique expression pattern: it is expressed in
virtually all neurons, but at the same time is also specific for neurons, to our knowledge the only transcription
factor known to be specific and pan-neuronal at the same time. Independent of the reprogramming work,
recent sequencing studies showed that MYT1L is frequently mutated in neuropsychiatric disease including
autism and schizophrenia. Nevertheless, very little is known about this gene. Not even a mouse knock-out has
been reported yet. We have therefore begun to investigate Myt1l's role in reprogramming and during normal
development. Our first insights about its molecular function suggest that Myt1l is important for neuronal
reprogramming and normal embryonic neurogenesis acting predominantly by transcriptional repression of non-
neuronal lineage programs.
The goal of this research project is to better understand the role of Myt1l in neurons after neurogenesis
is completed. We propose to investigate its role on the molecular, cellular circuit, and behavioral level using the
mouse as model system. We have intriguing preliminary data that about a third of high confidence autism-
causing chromatin factors are also candidate binding partners of Myt1l. This suggests that all these mutations
might converge on a hypothetical Myt1l-associated “chromatin pathway” which is dysfunctional in at least
subset of autism. This project will test this hypothesis and evaluate whether interference with the members of
this chromatin “pathway” might rectify molecular, cellular or behavioral phenotypes caused by Myt1l deletion.
Since chromatin modifying enzymes are in principle pharmacologically tractable the hope would be that a
functional intervention of such chromatin factors may be of therapeutic value for autistic children carrying
MYT1L mutations. We will therefore test throughout all our three aims whether manipulation of these chromatin
factors can rescue the molecular, cellular, or behavioral Myt1l phenotypes.
我们发现三种转录因子Ascl1、myt1样(Myt1l)和Brn2可以重编程成纤维细胞
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice.
- DOI:10.1186/s13229-022-00497-3
- 发表时间:2022-05-10
- 期刊:
- 影响因子:6.2
- 作者:
- 通讯作者:
Persistent transcriptional programmes are associated with remote memory.
- DOI:10.1038/s41586-020-2905-5
- 发表时间:2020-11
- 期刊:
- 影响因子:64.8
- 作者:
- 通讯作者:
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Thomas C. Sudhof其他文献
Single piconewton forces regulate dissociation of the Latrophilin-3 gain domain
- DOI:
10.1016/j.bpj.2022.11.696 - 发表时间:
2023-02-10 - 期刊:
- 影响因子:
- 作者:
Brian L. Zhong;Christina E. Lee;Vipul T. Vachharajani;Thomas C. Sudhof;Alexander R. Dunn - 通讯作者:
Alexander R. Dunn
Presynaptic Neurexin-3 Alternative Splicing Trans-Synaptically Controls Postsynaptic AMPA-Receptor Traficking
突触前 Neurexin-3 选择性剪接跨突触控制突触后 AMPA 受体运输
- DOI:
- 发表时间:
- 期刊:
- 影响因子:64.5
- 作者:
Jason Aoto;David C Martinelli;Robert C Malenka;Katsuhiko Tabuchi;Thomas C. Sudhof - 通讯作者:
Thomas C. Sudhof
Thomas C. Sudhof的其他文献
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{{ truncateString('Thomas C. Sudhof', 18)}}的其他基金
Latrophilin Function in Synapse Formation
Latrophilin 在突触形成中的功能
- 批准号:
10611452 - 财政年份:2021
- 资助金额:
$ 69.82万 - 项目类别:
Latrophilin Function in Synapse Formation
Latrophilin 在突触形成中的功能
- 批准号:
10434957 - 财政年份:2021
- 资助金额:
$ 69.82万 - 项目类别:
Regulation of cholesterol by y-secretase and ApoE: Implications for AD pathogenesis and synaptic function
γ-分泌酶和 ApoE 对胆固醇的调节:对 AD 发病机制和突触功能的影响
- 批准号:
10601030 - 财政年份:2021
- 资助金额:
$ 69.82万 - 项目类别:
Regulation of cholesterol by y-secretase and ApoE: Implications for AD pathogenesis and synaptic function
γ-分泌酶和 ApoE 对胆固醇的调节:对 AD 发病机制和突触功能的影响
- 批准号:
10379401 - 财政年份:2021
- 资助金额:
$ 69.82万 - 项目类别:
Latrophilin Function in Synapse Formation
Latrophilin 在突触形成中的功能
- 批准号:
10274019 - 财政年份:2021
- 资助金额:
$ 69.82万 - 项目类别:
The role of Myt1l in the developing and adult mouse brain
Myt1l 在发育中和成年小鼠大脑中的作用
- 批准号:
9904331 - 财政年份:2019
- 资助金额:
$ 69.82万 - 项目类别:
The role of Myt1l in the developing and adult mouse brain
Myt1l 在发育中和成年小鼠大脑中的作用
- 批准号:
10333320 - 财政年份:2019
- 资助金额:
$ 69.82万 - 项目类别:
Control of long-term synaptic plasticity by neurexin ligands
神经毒素配体控制长期突触可塑性
- 批准号:
8854549 - 财政年份:2015
- 资助金额:
$ 69.82万 - 项目类别:
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