ME1 DURING NEURONAL DIFFERENTIATION

神经元分化期间的 ME1

• 批准号: 2272804
• 负责人: MAURICIO X ZUBER
• 金额: $ 20.05万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-06 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2272804
• 关键词: cell differentiation; cerebellum; developmental neurobiology; dimer; gene expression; genetic promoter element; genetic regulation; laboratory mouse; laboratory rabbit; neural growth associated protein; protein structure function; transcription factor

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.

这项提案的总体重点是治理 神经元分化。我们的研究以ME1为中心，它是 碱性-螺旋-环-螺旋(BHLH)转录因子 对于正常的大脑发育来说是必不可少的。A精神障碍包括 精神分裂症和抑郁症等疾病被认为有很大的 基因贡献，这项提案中的研究很可能将 会影响我们对精神障碍、其原因和 他们的治疗。我们最近克隆了与小鼠相对应的cDNA E盒结合蛋白(MES)。其中两个ME1a和ME1b是 ME1基因选择性剪接的结果。这些转录的 调节因子与果蝇bHLH蛋白无子代有关。因为 ME1与转录因子的高度同源性 人神经系统中细胞的测定和分化 果蝇，并由于其特有的mRNA表达模式 ME1在神经系统中发生神经元分化的区域； 它很可能在中国的发展中扮演着重要的角色。 神经系统。目标是进一步描述ME1的特征，以便 了解其在神经元分化过程中的作用。具体的 旨在确定ME1蛋白的空间和时间表达 并研究它们的分子和细胞作用机制。ME1 起二聚体和杂二聚体的作用。受ME1调控的基因有 被认为是二聚化伙伴的结果。因此，它是 最重要的是识别和表征细胞蛋白质 与ME1相互作用并确定受其调控的神经元基因 BHLH转录因子。最近，我们检测到了ME1杂二聚体 脑核提取中的合作伙伴(MHP)。另外，我们的结果是 表明GAP-43启动子受E-box中ME1的调控 依赖的态度。GAP-43是一种神经元特异性生长相关蛋白 蛋白。建议进行的研究将开始定义结构- ME1和MHPS的功能和转录特性。一起， 这些研究将有助于确定分子和细胞属性 ME1和MHPS的表达，显著提高了我们对神经元差异的认识 国际关系。