Modeling Histone Demethylase Function in Neurogenesis

摘要 大脑皮层的发育依赖于关键基因的协调表达， 功能在发育过程中这些关键基因表达的改变可以导致复杂的 神经系统疾病表观遗传学机制动态调节关键基因的表达， 功能丧失会破坏皮层发育并导致大脑紊乱。罕见致病性 表观遗传因子KDM3B的突变与智力残疾和自闭症谱系有关 自闭症（ASD）。这个探索性的建议将测试这些KDM3B的功能后果 使用具有KDM3B突变的人胚胎干细胞对皮质发育的影响。我们 将研究突变体和对照细胞之间的细胞和分子差异，因为它们 分化成神经祖细胞和神经元。将这些细胞数据与分子数据相结合 数据将揭示KDM3B中智力残疾相关突变的直接影响， 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.