Role of TET3-mediated 5mC oxidation for neuronal differentiation and plasticity (B05)

在前一个资助阶段的基础上，我们将研究Rax-Tet3基因敲除小鼠活跃的视锥感光细胞发育的机制(目标A)。在目的B中，我们将研究TET3和DNA去甲基化在人IPSCs分化为3D视网膜器官中的作用。从这两个目标，我们期望获得新的分子洞察TET3介导的氧化修饰胞嘧啶在神经元中的作用。在目标C中，我们将研究单个Tet亚型和TET3相互作用蛋白在神经元分化过程中对5mC-5hmC-5fC周转的贡献。

Building on the results of the previous funding period, we will investigate the mechanism of exuberant cone photoreceptor development in Rax-Tet3 knockout mice (Aim A). In Aim B we will investigate the role of TET3 and DNA demethylation in the differentiation of human iPSCs into 3D retinal organoids. From both Aims we expect to gain new molecular insights into the role of TET3-mediated oxidation of modified cytosines in neurons. In Aim C we will investigate the contribution of individual TET isoforms and TET3 interacting proteins to the 5mC-5hmC-5fC turnover during neuronal differentiation.