Functional Interrogation of Chromatin Remodeling Gene in Brain Development

大脑发育中染色质重塑基因的功能探究

基本信息

  • 批准号:
    RGPIN-2020-04872
  • 负责人:
  • 金额:
    $ 2.7万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2022
  • 资助国家:
    加拿大
  • 起止时间:
    2022-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

Background | Development of nerve cells and the formation of the mammalian brain is precisely organized by gene expression. Gene transcription is regulated by groups transcriptional factors (TFs) and many epigenetic factors, including chromatin remodeling proteins. While a wealth of knowledge exists about how TFs regulate various developmental processes and functional outcomes of specific cell types the mammalian brain, little is known about the contribution of chromatin remodeling proteins in such processes. Objectives and Approaches | Our aims in this NSERC DG are to examine how one of these proteins, Chd8, controls the transcriptome of neuronal subtypes and what impact this has on the morphological development of these sub-types, and how this, in turn, affects physiological function. We will cross mouse harboring Chd8fl/fl together with Rosa 26-td-tomato and cell-type-specific Cre lines in this project. We will start with neuronal, and glial subtype-specific Cre lines, including NEX-Cre, VIAAT-Cre, and GFAP-Cre. Our specific aims are: - Aim 1: To identify and compare the genome-wide, transcriptional signature, after removing of Chd8 in specific types of brain cells. The deletion of Chd8 and simultaneously labeling with td-tomato allows us to analyze a homogeneous population of cells from brain tissues, and to carry out genome-wide transcriptional analysis using RNA-Seq. - Aim 2: To determine the morphological alterations caused by completely Chd8 deletion in specific types of neurons. We will carry out assays to examine the survival, migration, dendritic outgrowth and synaptic density resulting from removal of Cdh8. - Aim 3: To determine the functional outcomes caused by completely knocking out of Chd8 in subtypes of cells. We will characterize both excitatory and inhibitory neurons on their firing of action potential, excitatory and inhibitory inputs using slice electrophysiology. Outcomes and Significance | This NSERC DG will lead to the training of Highly Qualified Personnel, including one postdoc fellow and two Ph.D. students who will leave my lab armed with substantial expertise in neuroscience research. These experiments will provide a direct, in vivo evidence regarding how a chromatin regulator (Chd8 gene) contribute to subtype-specific transcriptome, and endow neurons and glial cells with diverse, complex properties, which will enable a comprehensive picture for the genetic regulation of brain development in mammals. The results, insights, and methods that will come out of our studies will provide a tractable strategy for addressing the rules by which specific chromatin-remodeling proteins can lead to unique neuronal and glial subtype specification in the future, which is a fundamental question in neuroscience, and a long-term goal of my lab.
神经细胞的发育和哺乳动物大脑的形成是由基因表达精确组织的。基因转录受群转录因子(TFs)和许多表观遗传因子(包括染色质重塑蛋白)的调控。虽然关于tf如何调节哺乳动物大脑特定细胞类型的各种发育过程和功能结果的知识丰富,但对染色质重塑蛋白在这些过程中的贡献知之甚少。我们在NSERC DG中的目标是研究这些蛋白质之一Chd8如何控制神经元亚型的转录组,以及这对这些亚型的形态发育有什么影响,以及这反过来如何影响生理功能。在本项目中,我们将携带Chd8fl/fl的小鼠与Rosa 26-td-tomato和细胞类型特异性Cre系杂交。我们将从神经元和胶质亚型特异性Cre系开始,包括NEX-Cre, VIAAT-Cre和gmap -Cre。我们的具体目标是:目标1:在特定类型的脑细胞中去除Chd8后,识别和比较全基因组的转录特征。删除Chd8并同时标记td-tomato使我们能够分析来自脑组织的均匀细胞群,并使用RNA-Seq进行全基因组转录分析。目的2:确定Chd8完全缺失在特定类型神经元中引起的形态学改变。我们将进行检测去除Cdh8后的存活、迁移、树突生长和突触密度。-目的3:确定在细胞亚型中完全敲除Chd8所引起的功能结果。我们将描述兴奋性和抑制性神经元的动作电位发射,兴奋性和抑制性输入使用切片电生理学。结果和意义| NSERC DG将培养高素质人才,包括一名博士后和两名博士生,他们将带着神经科学研究的大量专业知识离开我的实验室。这些实验将提供直接的活体证据,证明染色质调节因子(Chd8基因)如何促进亚型特异性转录组,并赋予神经元和神经胶质细胞多样化、复杂的特性,这将使人们能够全面了解哺乳动物大脑发育的遗传调控。我们研究的结果、见解和方法将为解决特定染色质重塑蛋白在未来导致独特的神经元和胶质亚型规范的规则提供一个易于处理的策略,这是神经科学的一个基本问题,也是我实验室的长期目标。

项目成果

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Zhou, Yang其他文献

Comments on "Effects of refractive accommodation on subfoveal choroidal thickness in silicone oil-filled eyes" BMC Ophthalmology (2022) 22:107 https://doi.org/10.1186/s12886-022-02332-y.
  • DOI:
    10.1186/s12886-022-02696-1
  • 发表时间:
    2022-12-08
  • 期刊:
  • 影响因子:
    2
  • 作者:
    Gao, Lei;Zhou, Yang;Liu, Guangsen
  • 通讯作者:
    Liu, Guangsen
Tunable Toxicity of Bufadienolides is Regulated through a Configuration Inversion Catalyzed by a Short-Chain Dehydrogenase/Reductase.
  • DOI:
    10.1002/cbic.202200473
  • 发表时间:
    2022-11-18
  • 期刊:
  • 影响因子:
    3.2
  • 作者:
    Ye, Ge;Huang, Weihuan;Chen, Zeping;Zhong, Hao;Zhong, Junhao;Guo, Xiaoxin;Huang, Yuheng;Kandalai, Shruthi;Zhou, Xiaozhuang;Zhang, Nan;Zhou, Yang;Zheng, Qingfei;Tian, Haiyan
  • 通讯作者:
    Tian, Haiyan
The efficacy of modified HuangLian JieDu decoction for early enteral nutrition in patients with sepsis: A randomized controlled study.
黄连解毒汤加减对脓毒症患者早期肠内营养的疗效:随机对照研究。
  • DOI:
    10.1097/md.0000000000032583
  • 发表时间:
    2022-12-30
  • 期刊:
  • 影响因子:
    1.6
  • 作者:
    Wang, Yifei;Li, Yue;Ye, Yanyang;Xuan, Lusha;Xu, Lijie;Li, Guofa;Zhou, Yang;Ma, Huanggang;Zhou, Lingjie;Chen, Yanjun;Wu, Weifei;Zhu, Weidong;Zhang, Yunhua
  • 通讯作者:
    Zhang, Yunhua
Cavitation as a mechanism of substrate discrimination by adenylosuccinate synthetases
  • DOI:
    10.1021/bi0607498
  • 发表时间:
    2006-09-26
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Iancu, Cristina V.;Zhou, Yang;Honzatko, Richard B.
  • 通讯作者:
    Honzatko, Richard B.
Genetic diversity of Venturia carpophila populations from different hosts and geographic regions in China.
  • DOI:
    10.3389/fmicb.2022.985691
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Zhou, Yang;Chaisiri, Chingchai;Luo, Mei;Fan, Fei;Wang, Yu-Fu;Yin, Liang-Fen;Yin, Wei-Xiao;Luo, Chao-Xi
  • 通讯作者:
    Luo, Chao-Xi

Zhou, Yang的其他文献

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{{ truncateString('Zhou, Yang', 18)}}的其他基金

Functional Interrogation of Chromatin Remodeling Gene in Brain Development
大脑发育中染色质重塑基因的功能探究
  • 批准号:
    RGPIN-2020-04872
  • 财政年份:
    2021
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Grants Program - Individual
Functional Interrogation of Chromatin Remodeling Gene in Brain Development
大脑发育中染色质重塑基因的功能探究
  • 批准号:
    DGECR-2020-00030
  • 财政年份:
    2020
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Launch Supplement
Functional Interrogation of Chromatin Remodeling Gene in Brain Development
大脑发育中染色质重塑基因的功能探究
  • 批准号:
    RGPIN-2020-04872
  • 财政年份:
    2020
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Grants Program - Individual
Computational identification of synonymous sites under selection
选择下同义位点的计算识别
  • 批准号:
    447892-2013
  • 财政年份:
    2013
  • 资助金额:
    $ 2.7万
  • 项目类别:
    University Undergraduate Student Research Awards
multifunctional biobased polymeric composites
多功能生物基高分子复合材料
  • 批准号:
    448737-2013
  • 财政年份:
    2013
  • 资助金额:
    $ 2.7万
  • 项目类别:
    University Undergraduate Student Research Awards
Identification of mRNA localization signals
mRNA定位信号的鉴定
  • 批准号:
    432096-2012
  • 财政年份:
    2012
  • 资助金额:
    $ 2.7万
  • 项目类别:
    University Undergraduate Student Research Awards

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