Regulation of Olig2 in Motor Neuron Development

描述（由申请人提供）： bHLH转录因子编码基因Olig1和Olig2在中枢神经系统（CNS）发育过程中发挥重要作用。在脊髓中，Olig2是运动神经元和少突胶质细胞的模式形成特化所必需的。在这个Kirschstein国家研究服务奖奖学金申请，我提出的研究旨在产生一个详细的了解Olig2调节在神经发育的早期阶段。最近，我们已经确定了一个3.6 kb的调控元件，特别是在运动神经元祖细胞中的Olig2表达。这种增强子调节Olig2表达的机制尚不清楚。我的目标是确定与增强子相互作用的反式作用转录因子。这项研究将解决神经模式的形成和神经元与神经胶质细胞的命运规范的基本问题。这些实验直接解决了哺乳动物中与再生相关的问题，并最终修复了在神经系统疾病中被破坏的神经元件。

DESCRIPTION (provided by applicant): The bHLH transcription factor-encoding genes, Olig1 and Olig2, have essential roles during central nervous system (CNS) development. In the spinal cord, Olig2 is required for pattern formation specification of motor neurons and oligodendrocytes. In this Kirschstein National Research Service Award Fellowship Application, I propose studies intended to yield a detailed understanding of Olig2 regulation during early stages of neural development. Recently, we have identified a 3.6 kb regulatory element that governs Olig2 expression specifically in motor neuron progenitors. The mechanism by which this enhancer regulates expression of Olig2 is unknown. My objective is to identify trans-acting transcription factors that interact with the enhancer. This research will address fundamental issues of neural pattern formation and neuronal versus glial cell fate specification. These experiments directly address issues in mammals related to regrowth and eventually the repair of neural elements destroyed in neurologic diseases.