转录因子Pou3f1在小鼠早期胚胎神经命运决定中的功能和机制研究

项目名称： 转录因子Pou3f1在小鼠早期胚胎神经命运决定中的功能和机制研究

项目编号： No.31501173

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 宋璐

作者单位： 中国科学院上海生命科学研究院

项目金额： 20万元

中文摘要： 脊椎动物早期发育中，外、中、内三胚层经过原肠运动初步形成。外胚层前部细胞进一步发育为神经外胚层。已有研究发现，外胚层细胞能够在缺失外源抑制信号如BMPs和Wnt信号的情况下，自主选择神经命运。但除了外源神经抑制信号外，神经外胚层分化还需要内源神经命运促进因子的参与。我们已发表研究显示，Pou3f1是小鼠胚胎干细胞神经分化的必需因子。然而，Pou3f1在小鼠胚胎发育中的功能及Pou3f1发挥促神经功能的详细机制还不清楚。本项目前期工作已经构建了Pou3f1敲除的小鼠。在此基础上，本项目旨在分析Pou3f1敲除小鼠在早期神经发育中的表型，并运用多能干细胞神经分化模型寻找Pou3f1发挥促神经作用的辅助因子及下游基因，进一步通过胚胎电转及胚胎培养等体内实验验证，最终构建Pou3f1发挥促神经作用的分子模型。本项目的研究成果将有利于建立更加科学完善的早期胚胎神经发育中重要因子的调控网络和研究方法。

中文关键词： 小鼠；外胚层；神经系统；转录因子；基因表达调控

英文摘要： Early vertebrate development is a process by which unrestricted pluripotent stem cells progressively make lineage fate choices. Three germ layers including ectoderm, mesoderm, and endoderm, are generated during gastrulation. Ectoderm is then specified to the neural fate and develops into neuroectoderm. Previous studies have indicated that neural fate specification from ectoderm takes place autonomously in the absence of inhibitory signals such as bone morphogenetic proteins (BMPs) and Wnt. In addition to extrinsic signaling pathways, neuroectoderm specification is also controlled by the sequential activation of intrinsic neural fate-promoting factors. Our published study shows that Pou3f1 is an essential factor for neural differentiation of embryonic stem cells (ESCs). However, it remains unclear about the function and mechanism of Pou3f1 in early mouse embryo. In our previous study, Pou3f1 knock out mouse have been constructed. Here, we propose to analysis the phenotype of Pou3f1 knock out mouse, then using of the ESC neural differentiation assay to search the co-factor and downstream target genes of Pou3f1. Further analysis of mouse embryo-electroporation and embryo-culture studies will help to establish the molecular model of Pou3f1, which hopefully contribute to elucidation of the regulatory network and research method in early neural development.

英文关键词： Mouse;Ectoderm;Neural system ;Transcription factors;Gene expression regulation