Regulation of Olig2 in Motor Neuron Development

描述(由申请人提供)： 在中枢神经系统(CNS)发育过程中，bHLH转录因子编码基因Opol1和Olob2起着重要的作用。在脊髓中，运动神经元和少突胶质细胞的模式形成规范需要寡核苷酸2。在这份Kirschstein国家研究服务奖奖学金申请中，我提议进行研究，旨在详细了解神经发育早期阶段的寡聚2调节。最近，我们发现了一个3.6kb的调控元件，它特异性地调控运动神经元前体细胞中Orig2的表达。该增强子调节Orig2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形成和神经元与神经胶质细胞命运指定的基本问题。这些实验直接解决了哺乳动物中与再生有关的问题，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.