Modeling Histone Demethylase Function in Neurogenesis

摘要 皮质发育依赖于正确认知的关键基因的协调表达 功能。这些关键基因在发育过程中表达的改变可能会导致复杂的结果 神经系统疾病。表观遗传机制动态调节关键基因及其表达 功能丧失会扰乱皮质发育并导致大脑疾病。罕见致病性 一种表观遗传因子 KDM3B 的突变与智力障碍和自闭症谱系相关 障碍（ASD）。该探索性提案将测试这些 KDM3B 的功能后果 使用带有 KDM3B 突变的人类胚胎干细胞研究皮质发育的突变。我们 将研究突变细胞和对照细胞之间的细胞和分子差异，因为它们 分化为神经祖细胞和神经元。将这些细胞数据与分子数据整合 数据将揭示 KDM3B 中智力障碍相关突变对 神经发育。

ABSTRACT Cortical development is dependent on the coordinated expression of critical genes for proper cognitive function. Alterations in expression of these key genes during development can result in complex neurological diseases. Epigenetic mechanisms dynamically regulate expression of key genes and their loss of function disrupts cortical development and contributes to brain disorders. Rare pathogenic mutations in one epigenetic factor, KDM3B, are linked to intellectual disability and autism spectrum disorders (ASD). This exploratory proposal will test the functional consequences of these KDM3B mutations on cortical development using human embryonic stem cells with mutations of KDM3B. We will investigate both cellular and molecular differences between mutant and control cells as they differentiate into neural progenitor cells and neurons. Integration of these cellular data with molecular data will reveal the direct effects of intellectual disability related mutations in KDM3B to neurodevelopment.