Foxp-regulated signaling pathways in brain development - Diversity
大脑发育中 Foxp 调节的信号通路 - 多样性
基本信息
- 批准号:10478320
- 负责人:
- 金额:$ 8.02万
- 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:2022-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:Automobile DrivingBehaviorBehavioralBiological ModelsBrainBrain DiseasesCell NucleusCellsCerebral cortexChildhoodChromatinCorpus striatum structureCouplingDataDevelopmentElectrophysiology (science)EtiologyFOXP1 geneFOXP2 geneFamilyFundingGene ExpressionGene Expression RegulationGenesGenetic TranscriptionHeritabilityImpairmentIntellectual functioning disabilityJournalsLanguage DisordersLinkMental disordersMissionMolecularMusNational Institute of Mental HealthNatureNeurodevelopmental DisorderNeuronsNeurosciencesPhenotypePhysiologyPublishingRegulator GenesResearchResearch TrainingResolutionRiskRodent ModelRoleSignal PathwaySignal TransductionSmall Nuclear RNASpeechTechnologyTimeTrainingVariantWorkXCL1 geneautism spectrum disorderbasecell typeexperimental studygenomic datainsightmembermigrationneurogenomicsneuropsychiatric disorderparent grantprogramssingle-cell RNA sequencingskillstargeted treatmenttranscription factortranscriptome sequencing
项目摘要
RESEARCH AND TRAINING PLAN FOR RACHAEL VOLLMER
A. SUMMARY OF THE FUNDED GRANT
The parent grant (R01MH126481; funding period 06/01/21-05/31/2026) is titled: “Foxp-regulated signaling
pathways in brain development.” Two members of the FOXP family of transcription factors, FOXP1 and FOXP2,
have been linked to monogenetic forms of intellectual disability, autism spectrum disorders, and specific speech
and language deficits. Variants in FOXP1 or FOXP2 are among the most significant genes associated with
autism spectrum disorders. We previously showed that Foxp1 and Foxp2 both have significant contributions to
cortical and striatal development. We linked these developmental changes via studies of gene expression,
electrophysiology, and behaviors. We further identified non-cell-autonomous changes in gene expression using
newly available single-cell RNA-sequencing technology. Based on these data, the central hypothesis driving the
work in the parent grant and the proposed supplement is that Foxp1 and Foxp2 are key orchestrators of
transcriptional signaling cascades in a cell type-specific manner that are important for neuronal function and are
at risk in neurodevelopmental disorders such as autism. We propose to identify these cell type-specific
contributions in the developing cortex by using rodent models through two specific aims that will utilize snATAC-
seq: 1) Determine the cell type-specific gene regulatory programs orchestrated by Foxp1 in the developing
cortex; and 2) Determine the cell type-specific gene regulatory programs orchestrated by Foxp2 in the developing
cortex. Together, these aims will delineate the cell type contribution of both Foxp1 and Foxp2 to cortical
development. The rodent models and cell-type specific genomic datasets will provide insight into the basic
molecular mechanisms governing normal mammalian brain development. These research aims support the
mission of the NIMH to understand and develop treatments for mental disorders. Finally, the training plan that
we have described in this proposal will provide Ms. Vollmer with a cutting-edge skill set in neurogenomics.
Aims 1 and 2 of the parent grant are to identify the cell-type specific developmental transcriptional program
regulated by Foxp1 or Foxp2 in the mouse brain using single-nuclei RNA-sequencing (snRNA-seq) at several
time points. These experiments will utilize previously generated Foxp1 and Foxp2 cKO mice already generated
and published using Emx1.Cre (e.g. Araujo et al., Journal of Neuroscience 2017; Usui et al., Genes &
Development 2017; Co et al., Cerebral Cortex 2020). Our lab has also recently applied the approach of single-
nuclei ATAC-sequencing to uncover the cell type specific contributions of gene regulation and signaling
cascades (e.g. Berto et al., Nature Neuroscience 2021). Coupling this chromatin accessibility approach with
gene expression at the cell type level, should provide a new level of resolution for understanding how these
transcription factors organize developmental signaling cascades. As described below, Rachael Vollmer will
advance the aims of the parent grant by using the same Foxp1 and Foxp2 cKO mice proposed for snRNA-seq;
however, she will apply snATAC-seq at the same timepoints to understand chromatin accessibility. This cell-
specific approach will allow us to narrow down the direct transcriptional targets of Foxp1 and Foxp2 driving the
observed phenotypes in these model systems such as impaired cortical migration and behavioral inflexibility.
瑞秋·沃尔默的研究和培训计划
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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Genevieve Konopka其他文献
Genevieve Konopka的其他文献
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{{ truncateString('Genevieve Konopka', 18)}}的其他基金
Deciphering the genomic mechanisms underlying the physiology of human brain stimulation
破译人脑刺激生理学背后的基因组机制
- 批准号:
10559426 - 财政年份:2022
- 资助金额:
$ 8.02万 - 项目类别:
Foxp-regulated signaling pathways in brain development
大脑发育中 Foxp 调节的信号通路
- 批准号:
10425442 - 财政年份:2021
- 资助金额:
$ 8.02万 - 项目类别:
Foxp-regulated signaling pathways in brain development
大脑发育中 Foxp 调节的信号通路
- 批准号:
10630270 - 财政年份:2021
- 资助金额:
$ 8.02万 - 项目类别:
Foxp-regulated signaling pathways in brain development
大脑发育中 Foxp 调节的信号通路
- 批准号:
10799082 - 财政年份:2021
- 资助金额:
$ 8.02万 - 项目类别:
Foxp-regulated signaling pathways in brain development
大脑发育中 Foxp 调节的信号通路
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10799021 - 财政年份:2021
- 资助金额:
$ 8.02万 - 项目类别:
Foxp-regulated signaling pathways in brain development
大脑发育中 Foxp 调节的信号通路
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10315542 - 财政年份:2021
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Identification of human genomic signatures of episodic memory
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$ 8.02万 - 项目类别:
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