ROLE OF THE MED1 SUBUNIT OF MEDIATOR CO-ACTIVATOR COMPLEX IN NEURAL STEM CELLS

摘要 介体共激活复合物（Mediator）是一种25 - 30蛋白质复合物，在免疫调节中起着关键作用。 调节真核细胞中的基因转录。介体在脑细胞中表达，但目前其精确的 功能尚未定义。特别是我们缺乏对中介子单位的作用的理解， 与神经转录因子相互作用。在这个试点项目中，我们将调查中介1的功能 亚基（Med1）的神经干细胞中使用条件Med1敲除小鼠。我们将确定神经干 细胞在缺乏Med1的情况下存活。我们还将结合体内和细胞培养分析来确定 由于缺乏Med1而受到干扰的基本生物过程。这些实验将让我们首先看到 Med1在神经干细胞中作用，并为将来的大规模研究提供了框架 介体亚单位。基因转录是神经细胞生命的一个基本方面，而Mediator可能是一个 许多人类神经遗传性疾病是由中介子亚基突变引起的， 工作与临床和转化神经科学高度相关。

ABSTRACT The Mediator Co-activator Complex (Mediator) is a 25-30 protein complex that plays a pivotal role in regulating gene transcription in eukaryotic cells. Mediator is expressed in brain cells but currently its precise functions have not been defined. In particular we lack of understanding of the roles of Mediator subunits that interact with neural transcription factors. In this pilot project we'll investigate the function of the Mediator1 subunit (Med1) in neural stem cells using conditional Med1 knockout mice. We will determine if neural stem cells survive in absence of Med1. We will also use a combination of in vivo and cell culture analyses to define the basic biological processes that are perturbed by lack of Med1. These experiments will give a first look at the role of Med1 in neural stem cells and provide a framework for future large-scale studies of this and other Mediator subunits. Gene transcription is a fundamental aspect of neural cell life and Mediator is likely to be an integral part of it. A number of human neural genetic disorders arise from mutation of Mediator subunits so this work is highly relevant to clinical and translational neuroscience.