ME1 DURING NEURONAL DIFFERENTIATION

本提案的总体重点是管理机制 神经元分化 我们的研究集中在ME 1上， 碱性螺旋环螺旋（bHLH）转录因子，已知其 对大脑的正常发育至关重要 精神障碍包括 精神分裂症和抑郁症等，据信有很大的 基因的贡献，很可能这项建议中的研究将 影响了我们对精神障碍及其原因的理解， 他们的治疗 我们最近克隆了对应于 E盒结合蛋白（ME）。 其中两个ME，ME 1a和ME 1b是 这是ME 1基因选择性剪接的结果。 这些转录 调节子与果蝇bHLH蛋白Daughterless相关。 因为 ME 1与转录因子的高度同源性， 神经系统中的细胞决定和分化 果蝇，并且由于特征性的mRNA表达模式， ME 1在发生神经元分化的神经系统区域中; 它可能在发展中发挥重要作用， 神经系统 目标是进一步表征ME 1，以便 了解它在神经元分化过程中的功能。 具体 目的是确定ME 1蛋白的时空表达， 并研究其分子和细胞作用机制。 ME1 作为二聚体和异二聚体发挥作用。 受ME 1调控的基因是 被认为是二聚化伴侣的结果。 因此有 最重要的是识别和表征细胞蛋白质， 与ME 1相互作用，并确定由这些基因调控的神经元基因。 bHLH转录因子。 最近，我们检测到ME 1异二聚体 伴侣（MHP）在脑核提取物。 此外，我们的结果 表明差距-43启动子在E-box中受ME 1调控 依赖的方式。 GAP-43是一种神经元特异性生长相关蛋白， 蛋白 建议进行研究，开始确定结构- ME 1和MHP的功能和转录特征。 在一起， 这些研究将有助于确定分子和细胞特性 ME 1和MHPs的表达，并显著提高了我们对神经元差异的认识。 iation。

The general focus of this proposal is on the mechanisms that govern neuronal differentiation. Our studies are centered on ME1, one of the basic-helix-loop-helix (bHLH) transcription factors which are known to be essential for normal brain development. A mental disorders including schizophrenia and depression, among others, are believed to have a large genetic contribution, it is likely that the studies in this proposal will have an impact on our understanding of mental disorders, their causes and their treatments. We recently cloned cDNAs corresponding to the mouse E-box binding proteins (MEs). Two of these MEs, ME1a and ME1b are the result of alternative splicing of the ME1 gene. These transcriptional regulators are related to Drosophila bHLH protein Daughterless. Because of the strong homology of ME1 with transcription factors essential for cell determination and differentiation in the nervous system in Drosophila, and because of the characteristic mRNA expression pattern of ME1 in areas of the nervous system where neuronal differentiation occurs; it is likely that it plays an important role in development of the nervous system. The goal is to further characterize ME1 in order to understand its function during neuronal differentiation. The specific aims ar to determine the spatial and temporal expression of ME1 proteins and to study their molecular and cellular mechanism of action. ME1 functions as a dimer and as heterodimer. The genes regulated by ME1 are thought to be the results of the dimerization partner. Therefore, it is most important to identify and characterize the cellular proteins that interact with ME1 and to identify the neuronal genes regulated by these bHLH transcription factors. Recently, we have detected ME1 heterodimer partners (MHPs) in brain nuclear extracts. In addition, our results indicate that the GAP-43 promoter is regulated by ME1 in an E-box dependent manner. GAP-43 is a neuronal specific growth associated protein. Studies are proposed that will begin to define the structure- function and transcriptional characteristic of ME1 and MHPs. Together, these studies will help to define the molecular and cellular properties of ME1 and MHPs and significantly advance our knowledge of neuronal differe iation.