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，而其他的则保持沉默。在神经系统中 结果是分化的细胞类型的发展和维持 基因表达的时间和空间特征模式 编码神经元表型特征。这样做的长期目标是 研究目的是阐明控制细胞死亡的分子机制。 神经递质基因的细胞特异性和发育调控。 神经肽血管活性肠肽(VIP)将被研究为 一种神经递质模型。VIP是一种由28个氨基酸组成的多肽 存在于中枢神经、外周神经和肠神经的神经元 系统，稀疏分布于肾上腺髓质细胞内，异位分布于 一些起源于神经脊的肿瘤。就像其他神经递质一样 基因，VIP基因的转录也可能被控制在反式- 在突触上。为实现以下目标提出了三个具体目标 这项研究。首先，血管活性肠肽基因中需要的序列 细胞特异性表达及其与之相关的蛋白质因子 互动将被确定。对于这些研究，假定的监管机构 VIP基因的区域将通过缺失和突变而被解剖 分析，融合到一个易于分析的转录报告基因和 在含有VIP的细胞中检测生物活性 转基因小鼠。其次，我们将检验这一假设 血管活性肠肽基因在卵巢癌中的时空表达特征 啮齿动物神经系统可归因于VIP细胞的合成- 特定的蛋白质因子。第三，将确定是否合作 细胞特异性因子和核心启动子因子之间的相互作用是 在VIP基因的细胞特异性转录控制中起重要作用。 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个顺式作用的理解 基因元件组合技术控制基因转录 神经细胞。这些研究还将为 了解控制外观的分子事件 神经元表型特征的维持和异位生产 某些起源于神经脊的肿瘤中的神经递质。

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.