Molecular Genetics of Segment Determination in Drosophila

分子遗传学将被用来研究果蝇黑腹果蝇复杂的生物结构是如何构建的。果蝇的发育是通过基因表达的层级进行的，在其早期阶段，会产生节段性胚胎。在分割之后，由于同源异型选择器基因的作用，每个Metamere产生了特定的身份。这些基因的产物都含有DNA结合的同源结构域，可能通过转录调控一组靶基因来发挥功能。为了了解同源异型选择器基因如何指定特定的同源异构体特性，分离和研究这些靶基因是很重要的。它们将通过使用消减杂交程序被分离出来，该程序旨在识别过度表达特定同源异型选择器基因的动物(Ultrabithorax，Ubx)和低表达该基因的动物之间的基因表达差异。一旦被分离，我们将通过回答以下问题来对我们对这些基因的兴趣进行排名：它们的表达模式是否与野生动物中Ubx的表达相关？在同源异型选择器基因突变的动物(包括但不限于Ubx突变)中，它们的表达模式会发生变化吗？而且，这些基因中是否有任何基因映射到基因组中Ubx蛋白结合的位置或已知的同源异型基因所在的位置？我们将把重点放在那些符合这些标准的基因上。它们将在分子和基因上进一步表征，以确定它们在发育过程中如何发挥作用，以产生异构体身份。*/

Molecular genetics will be used to investigate how complex biological structures are constructed in the fruit fly, Drosophila melanogaster. The development of Drosophila proceeds via a hierarchy of gene expression which, in its early stages, generates segmented embryo. Following segmentation, each metamere develops a particular identity due to the action of the homeotic selector genes. The products of these genes all contain the DNA-binding homeodomain and probably function by transcriptionally regulating a set of target genes. To understand how homeotic selector genes specify particular metameric identities it is important to isolate and study these target genes. They will be isolated by using a subtractive hybridization procedure designed to identify differences in gene expression between animals that overexpress a particular homeotic selector gene (Ultrabithorax, Ubx) and animals that underexpress this gene. Once isolated, we will rank our interest in these genes by answering the following questions: Do their patterns of expression correlate with Ubx expression in wild type animals? Do their patterns of expression change in animals mutant for homeotic selector genes (including, but not limited to, Ubx mutations)? And, do any of these genes map to positions in the genome where Ubx proteins bind or to where known homeotic loci are located? We will focus on those genes that fulfill most of these criteria. They will be further characterized both molecularly and genetically to determine how they function during development to generate metameric identities.***//