REGULATION OF NEURAL GENE EXPRESSION

本项目的核心目标是将 来自不同学科的个人来研究表达 神经生物学感兴趣的基因，以了解它们的表达模式 行动、调节和表达。 很明显，基因作用可以是 在许多水平上受到调控，包括转录，RNA剪接， 翻译和翻译后加工/修饰 proteins. 同样清楚的是，诸如激素和生长/营养因子的试剂可以用于治疗癌症。 因子，产生于神经系统外（例如，在免疫和 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。 这种复杂的监管的一些后果是， 神经系统内部和外部的药剂是：（a） 前体细胞分化成神经系统特异性的细胞 （B）细胞群的增殖和/或程序性死亡， 在大脑中产生了特定的解剖和功能结构， 大脑，和（c）调制的生产重要的神经 导致细胞功能调节的系统特异性蛋白质。 一 这项建议的主要目标是确定基因表达的机制。 神经细胞中的表达受到调控，以了解 神经系统的活动是受调节的。 这个计划中的每一个项目都在接近神经基因的问题 在神经系统中的表达在不同的研究水平。 项目1的主要目标将是确定基因的重要性， 新纹状体的功能，包括假定的基因， 涉及亨廷顿氏病。 在项目2中，调节 两种主要髓鞘蛋白基因、髓鞘碱性蛋白 (MBP)和蛋白脂质蛋白。 在项目3中， 将确定MBP基因的多个启动子的阐明 以及类固醇影响蛋白质翻译的机制 将测定由这些启动子产生的转录物。 的焦点 项目4将是纯化和克隆一种淋巴细胞因子， 少突胶质细胞的增殖和分化。 在项目5中， 类固醇改变下丘脑结构的机制 发育中的大鼠将通过分离和利用 对大脑中的性二型核特异的cDNA。 总的来说，这些项目涉及合作， 组成研究小组的合作，寻求了解基因 分子、细胞和有机体水平的作用。

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.