Mosaic Xlr3 Gene Expression in the Female Embryonic Mouse Brain

描述(申请人提供)：男孩和女孩对阅读困难、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性别二型性不仅反映了性腺激素的影响，而且还反映了性染色体基因的直接作用。该项目考察了特定X染色体基因在雄性和雌性小鼠中的差异表达及其对大脑发育的影响，特别是在大脑皮层。这个项目的目的是验证Xlr3基因(编码染色质结合蛋白)的差异表达调控神经前体增殖、分化、迁移、下游基因表达和形态的假设。这一目标将通过三个具体目标来实现：(1)分析Xlr3基因在发育中的男性和女性大脑中的表达；(2)寻找Xlr3基因表达差异调控的下游基因；(3)通过体内胚胎大脑皮层功能获得和功能丧失的分析，表征Xlr3基因的神经发育功能。因此，该项目将阐明大脑发育中的性别差异，这些差异可能有助于疾病易感性。。

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. .