Studies on Role and Regulation of the Ventral Nervous SystemDefective Homeobox Gene During Drosophila Neurogenesis

腹神经系统缺陷同源盒基因在果蝇神经发生过程中的作用及调控研究

• 批准号: 9604413
• 负责人: Dervla Mellerick-Dressler
• 金额: $ 28.35万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9604413&HistoricalAwards=false
• 关键词: Studies; Role; Regulation; Ventral; Nervous

PI: Mellerick-Dressler IBN: 9604413 The central nervous system (CNS) of both vertebrates and flies is composed of thousands of nerve cells, or neurons, each uniquely positioned, that express a specific combination of neurotransmitters and ion channels, and make appropriate contact with other neurons and target cells. The aim of this research is to understand how individual cell identities are specified during nervous system development. Because of the complexity inherent in mammalian nervous system development defined by both cell numbers and cell types, CNS specification is being studied in the fruit fly, Drosophila melanogaster, in Dr. Mellerick-Dressler's laboratory. Although relatively simple, Drosophila has proven to be an elegant and highly relevant model for analyzing gene function. The primordium of the nervous system is patterned along both the dorsal-ventral axis and the anterior-posterior axis by a variety of genes that regulate gene expression. One of these genes, called ventral nervous system defective (vnd) or NK-2, is expressed in a restricted dorsal-ventral population of cells that give rise to neurons in both fly and mammalian embryos suggesting that this gene family directs patterning. Indeed, fly embryos die and the central nervous system develops abnormally when mutations are present in the vnd/NK-2 gene, indicating that this gene is critical for neural development. To test the hypothesis that vnd/NK-2 functions in neuronal patterning, existing vnd/NK-2 mutants will be examined for altered expression of genes that are normally expressed within the vnd/NK-2 expression domain. The functional significance of the temporal and spatially restricted pattern of vnd/NK-2 gene expression will be addressed by generating and analyzing two different types of genetically altered "transgenic" fly embryos -- one that expresses vnd/NK-2 in all cells, the second that over-expresses the gene within a restricted population of cells during CNS development. Finally, with the even tual aim of addressing whether expression of vnd/NK-2 is functionally significant after embryogenesis, the temporal and spatial localization of the vnd/NK-2 gene product will be determined in wild-type flies after embryonic CNS development. The working hypothesis underlying this research is that many aspects of vnd/NK-2 function and regulation are evolutionarily conserved. Thus, the results from this work may also contribute to understanding how vertebrate vnd/NK-2 like genes function during neural development.

脊椎动物和苍蝇的中枢神经系统（CNS）都是由成千上万的神经细胞或神经元组成的，每个神经元都有独特的定位，表达神经递质和离子通道的特定组合，并与其他神经元和靶细胞进行适当的接触。这项研究的目的是了解在神经系统发育过程中个体细胞身份是如何被指定的。由于哺乳动物神经系统发育的复杂性是由细胞数量和细胞类型决定的，因此Mellerick-Dressler博士的实验室正在研究果蝇（Drosophila melanogaster）的中枢神经系统规范。虽然相对简单，果蝇已经被证明是一个优雅的和高度相关的模型来分析基因功能。神经系统的原基沿背-腹轴和前后轴由多种调节基因表达的基因组成。其中一种基因，称为腹侧神经系统缺陷（vnd）或NK-2，在果蝇和哺乳动物胚胎中产生神经元的有限背腹侧细胞群中表达，这表明该基因家族指导模式。事实上，当vnd/NK-2基因发生突变时，果蝇胚胎死亡，中枢神经系统发育异常，这表明该基因对神经发育至关重要。为了验证vnd/NK-2在神经元模式中起作用的假设，将检查现有的vnd/NK-2突变体是否改变了通常在vnd/NK-2表达域内表达的基因的表达。vnd/NK-2基因表达时空受限模式的功能意义将通过生成和分析两种不同类型的转基因“转基因”果蝇胚胎来解决——一种在所有细胞中表达vnd/NK-2，另一种在中枢神经系统发育过程中在有限的细胞群中过度表达该基因。最后，为了解决vnd/NK-2在胚胎发生后是否具有功能意义，我们将确定vnd/NK-2基因产物在野生型果蝇胚胎中枢神经系统发育后的时空定位。这项研究的工作假设是，vnd/NK-2的功能和调控的许多方面是进化保守的。因此，这项工作的结果也可能有助于理解脊椎动物vnd/NK-2样基因在神经发育过程中的功能。