DEVELOPMENT REGULATION OF MYELIN BASIC PROTEIN GENE

髓鞘碱性蛋白（MBP）占蛋白质的30%以上， 中枢神经系统中的髓鞘和10%的这些蛋白质 在周围神经系统中。 MBP仅在神经胶质细胞中产生， 以及中枢和外周神经系统中的雪旺氏细胞， 分别 最近的研究表明，单个基因编码 家庭的MBP和各种形式的MBP是由一个 mRNA的选择性剪接机制。 MBP的表达是 已知在大脑发育过程中受到不同的调节。 然而，在这方面， 控制该基因组织特异性转录的机制 在髓鞘形成过程中的作用仍然未知。 MBP调控区分析 揭示了一个小的11个核苷酸序列位于近端 相对于RNA起始的激活序列位置-14至-50 位点显著有助于MBP的细胞特异性活化， 神经胶质细胞 本提案中概述的研究的中心目标 是为了确定MBP基因是通过什么分子途径 在神经胶质细胞中受到转录调控。 实验设计 包括：（1）确定协调一致的调节因素 在细胞中具有近端序列控制MBP启动子， 阶段特异性的方式，（2）分子克隆编码这种基因 调节蛋白，并研究其结构和功能 蛋白质，（3）分析该蛋白质在脑组织中的表达， 发展 从这些分析中获得的信息应增加 我们对调节转录的机制的理解， 神经细胞中的基因

Myelin basic protein (MBP) constitutes more than 30% of the proteins of the myelin sheath in the central nervous system and 10% of these proteins in the peripheral nervous system. MBP is produced exclusively in glial and Schwann cells in the central and peripheral nervous systems, respectively. Recent studies have shown that a single gene encodes the family of MBPs and that the various forms of MBPs are governed by a mechanism of alternative splicing of the mRNA. Expression of MBPs is known to be differentially regulated during brain development. However, the mechanisms that govern tissue-specific transcription of this gene during myelination remain unknown. Analysis of the MBP regulatory region revealed that a small 11-nucleotide sequence located in the proximal activating sequence position -14 to -50 with respect to the RNA start site significantly contributes to the cell-specific activation of MBP in glial cells. The central goal of the research outlined in this proposal is to identify the molecular pathway by which MBP gene is transcriptionally regulated in glial cells. The experimental design includes: (1 ) identification of the regulatory-factor(s) that in concert with the proximal sequence control MBP promoter in cell- and stage-specific manner, (2) molecularly cloning the genes encoding this regulatory protein and investigating structure and function of this protein, (3) analyzing expression of this protein during brain development. The information gained from these analyses should increase our understanding of the mechanisms that modulate transcription of the genes in neural cells.