Molecular Genetics of Segment Determination in Drosophila

分子遗传学将用于研究果蝇（Drosophila melanogaster）复杂的生物结构是如何构建的。果蝇的发育通过基因表达的层次结构进行，在其早期阶段，产生分节胚胎。在分割之后，由于同源选择基因的作用，每个元粒形成一个特定的身份。这些基因的产物都含有dna结合同源结构域，并可能通过转录调节一组靶基因发挥作用。为了了解同型选择基因如何指定特定的异聚特性，分离和研究这些靶基因是很重要的。它们将通过减法杂交程序分离出来，该程序旨在确定过度表达特定同型选择基因（Ultrabithorax, Ubx）的动物和低表达该基因的动物之间的基因表达差异。一旦分离出来，我们将通过回答以下问题来对这些基因进行排序：它们的表达模式是否与野生型动物中的Ubx表达相关？它们的表达模式在同源选择基因突变（包括但不限于Ubx突变）的动物中是否发生变化？这些基因中是否有一个与基因组中Ubx蛋白结合的位置或已知的同型同源位点相对应？我们将重点关注那些满足大多数这些标准的基因。我们将进一步对它们进行分子和遗传学表征，以确定它们在发育过程中如何发挥作用，从而产生异聚体特征

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.***//