REGULATION OF NEURAL GENE EXPRESSION

该计划项目的中心目标是将 从不同的学科来考察个人的表达 神经生物学感兴趣的基因，以了解它们的模式 行动、规则和表达。很明显，基因的作用可以 在多个水平上进行调控，包括转录、RNA剪接、 翻译，以及翻译后处理/修改 蛋白质。也很明显，激素和生长/营养等因素 在神经系统外产生的因子(例如，在免疫系统和 内分泌系统)可以调节神经系统内的基因表达 在重要的方面。这一复杂监管的一些后果是 神经系统内部和外部的药物是：(A) 神经前体细胞分化为神经系统特异的细胞 功能，(B)细胞群的增殖和/或程序性死亡 产生了特定的解剖和功能结构 大脑，以及(C)重要神经的产生的调节 导致细胞功能调节的系统特异性蛋白质。一个 这项提议的主要目标是确定基因 神经细胞中的表达受到调节，以了解其功能 在神经系统中是受调节的。 这份提案中的每个项目都在探讨神经基因的问题 在神经系统中表达的不同层次的研究。 项目1的主要目标将是确定在 新纹状体的功能，包括可能 与亨廷顿氏症有关。在项目2中，调节 髓鞘碱性蛋白两个主要髓鞘蛋白基因的表达 (MBP)和蛋白质脂蛋白，将被鉴定。在项目3中， MBP基因的多个启动子将被确定 以及类固醇影响细胞翻译的机制 这些发起人产生的成绩单将被确定。的关注点 项目4将提纯和克隆一种诱导淋巴细胞因子 少突胶质细胞的增殖和分化。在项目5中， 类固醇改变大鼠下丘脑结构的机制 通过分离和利用发育期大鼠进行检测 大脑中性二态核团特有的DNA。 总体而言，这些项目涉及到合作和 成分研究小组合作，寻求了解基因 在分子、细胞和生物体水平上的作用。

The central aim of this proposed Program Project is to bring together individuals from a variety of disciplines to examine the expression of genes of neurobiological interest in order to understand their mode of action, regulation, and expression. It is clear that gene action can be regulated at a number of levels, which include transcription, RNA splicing, translation, and the post-translational processing/modification of proteins. It is also clear that agents such as hormones and growth/trophic factors, produced outside the nervous system (e.g. in the immune and endocrine systems) can regulate gene expression within the nervous system in important ways. Some of the consequences of this complex regulation by agents internal and external to the nervous system are: (a) the differentiation of precursors into cells with nervous system-specific functions, (b) proliferation and/or programmed death of groups of cells to give rise to specific anatomical and functional structures within the brain, and (c) the modulation of the production of important nervous system-specific proteins that result in modulation of cell function. A major goal of this proposal is to determine the mechanisms by which gene expression in neural cells is regulated in order to understand how function in the nervous system is regulated. Each project in this proposal is approaching the question of neural gene expression in the nervous system at a different level of investigation. The major objective of Project 1 will be to identify genes of importance in the functioning of the neostriatum, including putative genes that might involve Huntington's Disease. In Project 2, genomic elements that regulate the expression of two major myelin protein genes, myelin basic protein (MBP) and proteolipid protein, will be identified. In Project 3, elucidation of the multiple promoters of the MBP gene will be determined and the mechanism by which steroids influence the translation of the transcripts produced from those promoters will be determined. The focus of Project 4 will be to purify and clone a lymphocyte factor that induces the proliferation and differentiation of oligodendrocytes. In Project 5, the mechanisms by which steroids change the hypothalamic structure in the developing rat will be examined through the isolation and utilization of cDNAs specific for a sexually dimorphic nucleus in the brain. Collectively, these projects, which involve the cooperation and collaboration of the component research groups, seek to understand gene action at the molecular, cellular, and organismal levels.