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Mosaic Xlr3 Gene Expression in the Female Embryonic Mouse Brain

雌性胚胎小鼠脑中马赛克 Xlr3 基因的表达

基本信息

批准号：
8600323
负责人：
Robert F Hevner
金额：
$ 23.46万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8600323
关键词：
Affect Attention deficit hyperactivity disorder Autistic Disorder Axon Behavior Binding Proteins Biological Assay Brain Cell Proliferation Regulation Cerebral cortex Chromatin Commit Complementary DNA Dendrites Dendritic Spines Development Disease Disease susceptibility Dyslexia Embryo Event Female Gene Expression Gene Targeting Genes Gonadal Hormones Gonadal Steroid Hormones In Situ Hybridization Label Major Depressive Disorder Mental Depression Messenger RNA Morphology Mus Neonatal Neuronal Differentiation Neurons Nuclear Proteins Parents Pattern Perinatal Play Population Predisposition Role Sex Bias Sex Characteristics Sex Chromosomes Staging Structure Testing Ventricular X Chromosome X Inactivation axon growth boys cell type dimorphism girls imprint in vivo interest loss of function male migration molecular marker nerve stem cell neurodevelopment neurogenesis neuropsychiatry overexpression public health relevance research study sexual dimorphism small hairpin RNA transcriptome sequencing transcriptomics

项目摘要

DESCRIPTION (provided by applicant): Boys and girls show differential susceptibility to diseases such as dyslexia, autism and attention deficit hyperactivity disorder, in part due to differences in brain development. Previous studies suggest that sexual dimorphisms of brain structure and gene expression reflect not only the influence of gonadal hormones, but also direct effects of sex chromosome genes. This project examines differential expression of specific X chromosome genes in male and female mice and their effects on brain development, especially in the cerebral cortex. This objective of this project is to test the hypothesis that differential expression of Xlr3 genes (which encode chromatin binding proteins) regulates neural precursor proliferation, differentiation, migration, downstream gene expression, and morphology. This objective will be accomplished through 3 Specific Aims: (1) analyze the expression of Xlr3 genes in developing male and female brains; (2) identify downstream genes regulated by differential Xlr3 expression; and (3) characterize neurodevelopmental functions of Xlr3 genes through gain- and loss-of-function assays in embryonic cerebral cortex in vivo. This project will thus elucidate gender differences in brain development that may contribute to disease susceptibility. .

描述（由申请人提供）：男孩和女孩对阅读障碍、自闭症和注意力缺陷多动障碍等疾病的易感性不同，部分原因是大脑发育的差异。以往的研究表明，脑结构和基因表达的两性二态现象不仅反映了性腺激素的影响，还反映了性染色体基因的直接作用。本项目研究雄性和雌性小鼠特定X染色体基因的差异表达及其对大脑发育的影响，特别是在大脑皮层。该项目的目的是验证Xlr3基因（编码染色质结合蛋白）的差异表达调节神经前体增殖、分化、迁移、下游基因表达和形态的假设。这一目标将通过3个具体目标来实现：(1)分析Xlr3基因在发育中的男性和女性大脑中的表达；(2)鉴定受Xlr3差异表达调控的下游基因；(3)通过体内胚胎大脑皮层的功能获得和功能丧失测定来表征Xlr3基因的神经发育功能。因此，这个项目将阐明大脑发育中的性别差异，这可能有助于疾病的易感性。