REGULATION OF VIP GENE EXPRESSION IN NEURAL CELLS

分化的真核细胞能够选择性地表达 特定的基因，而其他人保持沉默。 在神经系统中， 分化细胞类型的发育和维持是 基因表达的时间和空间模式 编码神经元表型特征。 长期目标是 研究的目的是阐明控制这种疾病的分子机制。 神经递质基因的细胞特异性和发育调节。 神经肽血管活性肠肽（VIP）将作为 一种典型的神经递质 VIP是28个氨基酸的肽， 存在于中枢、外周和肠神经的神经元中 系统，肾上腺髓质细胞稀疏，异位， 一些神经嵴起源的肿瘤 就像其他神经递质一样 基因，VIP基因的转录也可以被控制反式- 突触上 为实现以下目标，提出了三个具体目标： 本研究 首先，VIP基因中的序列， 细胞特异性表达和与之相关的蛋白因子 互动将被识别。在这些研究中，假定的调节 VIP基因的区域将通过缺失和突变来解剖 分析，融合到一个易于分析的转录报告基因， 在含有VIP的细胞中测试生物活性， 转基因小鼠 第二，假设将被检验， VIP基因的特征性时空表达 啮齿动物神经系统可归因于VIP细胞的合成- 特异性蛋白质因子。第三，确定是否合作 细胞特异性因子和核心启动子因子之间的相互作用， 在VIP基因的细胞特异性转录控制中很重要。 细胞特异性表达的分子机制的阐明 VIP基因将增加我们对多重顺式作用 基因元件组合控制基因转录， 神经细胞 这些研究还将提供一个框架， 了解控制外观的分子事件， 维持神经元表型性状和异位产生 神经嵴起源的一些肿瘤中的神经递质。

Differentiated eukaryotic cells are capable of selectively expressing specific genes while others remain silent. In the nervous system the development and maintenance of differentiated cell types is the result of characteristic temporal and spatial patterns of expression of genes encoding neuronal phenotypic traits. The long-term goal of this research is to elucidate the molecular mechanisms which control the cell-specific and developmental regulation of neurotransmitter genes. The neuropeptide vasoactive intestinal peptide (VIP) will be studied as a model neurotransmitter. VIP is a 28 amino acid peptide that is present in neurons of the central, peripheral and enteric nervous systems, sparsely in cells of the adrenal medulla and ectopically in some tumors of neural crest origin. Like some other neurotransmitter genes, transcription of the VIP gene may also be controlled trans- synaptically. Three specific aims are proposed to achieve the goal of this study. First, sequences in the VIP gene which are required for cell-specific expression and the protein factors with which they interact will be identified. For these studies, the putative regulatory regions of the VIP gene will be dissected by deletional and mutational analysis, fused to an easily assayable transcriptional reporter gene and tested for biological activity in VIP-containing cell lies and in transgenic mice. Second, the hypothesis will be tested that the characteristic temporal and spatial expression of the VIP gene in the rodent nervous system can be attributed to the synthesis of VIP cell- specific protei factors. Third, it will be determined if cooperative interactions between cell-specific factors ad core promotor factors, are important in the cell-specific transcriptional control of the VIP gene. Elucidation of the molecular mechanisms of cell-specific expression of the VIP gene will increase our understanding of how multiple cis-acting genetic elements art combinatorily to control gene transcription in neural cells. These studies will also provide a framework for understanding the molecular events that control the appearance and maintenance of neuronal phenotypic traits and the ectopic production of neurotransmitters in some tumors of neural crest origin.