Molecular Genetics of Segment Determination in Drosophila

9506206人类多细胞动物的发育需要所有细胞都有两种类型的信息：它们相对于邻居的位置(位置信息)和它们应该产生什么结构(身份信息)。在果蝇中，同源异型选择器基因连接这两条信息：它们的大顺式调节区解释位置信息，它们的蛋白产物通过调节下游靶基因的转录来控制细胞特性。为了了解同源异型基因如何决定身份，这些目标基因的特征很重要。因此，利用分子筛选法分离了同源异型靶基因。在这些靶点中，有一个可能的转录因子，它被预测为控制中枢神经系统中的神经母细胞身份，以及细胞骨架的一个潜在组成部分。有趣的是，这两个基因的人类同源基因与肿瘤发生有关，这表明在某些情况下，它们可以控制细胞分化和/或增殖。为了研究它们在果蝇发育过程中的野生型功能，将产生这些基因的功能缺失和功能获得突变。这些突变对胚胎形态和基因表达的影响将被分析。使用体内错误表达分析，将比较野生型和致癌形式的功能。此外，控制这些基因表达的顺式顺式调控序列将使用体内报告基因结构和体外DNA结合分析进行研究。总而言之，这些实验将提供对位置信息如何通过同源异型基因转换为身份信息的理解。***

9506206 Mann The development of a multicellular animal requires that all cells have two types of information: where they are relative to their neighbors (positional information) and what structure they should generate (identity information). In Drosophila melanogaster, the homeotic selector genes link these two pieces of information: their large cis regulatory regions interpret positional information and their protein products control cellular identities by regulating the transcription of downstream target genes. These target genes are important to characterize to understand how homeotic genes determine identities. Therefore, homeotic target genes were isolated using a molecular screen. Among these targets is a putative transcription factor that is predicted to control neuroblast identities in the central nervous system and a potential component of the cytoskeleton. Interestingly, the human homologs of both genes are implicated in oncogenesis, suggesting that, in some contexts, they can control cellular differentiation and/or proliferation. To investigate their wild type functions during Drosophila development, loss- and gain-of-function mutations of these genes will be generated. The consequences these mutations have on both embryonic morphology and gene expression will be analyzed. Using in vivo misexpression assays, the functions of the wild type and oncogenic forms will be compared. In addition, the homeotic-responsive cis regulatory sequences that control the expression of these genes will be studied using in vivo reporter gene constructs and in vitro DNA-binding assays. Together, these experiments will provide an understanding of how positional information is translated into identity information by the homeotic genes. ***