MOLECULAR BASIS FOR GENETIC CONTROL OF DEVELOPMENT

本研究旨在解决这一问题 基因如何决定高等动物的发育 果蝇 黑腹菌是尝试这种方法的首选生物 因为它的基因组是最小和最好的 定义，因为更多的基因指定的发展已经 分离，因为克隆的DNA可以很容易地插入到它的 生殖细胞。 该基金的重点是基因调控功能 由双胸类的同源异型Ubx基因编码的蛋白质 复合物（BX-C）和对该基因的调控的产物 其他基因。 这个基因提供了 具体说明发展路径的身份， 元粒包括胸托的后半部分和 腹部的最前部（第5和第6节）。 Ubx基因由一个78 kb的转录单位组成， 转录物被差异剪接以产生至少五种mRNA 编码Ubx蛋白家族，其特征在于恒定的N- C末端区域和可变的中心区域 在保守同源结构域编码的同源结构域上游， 盒子 该项目的一个目标是确定 控制他的差异剪接 另一个是定义 每种蛋白质都能与 调节其靶基因的表达，其中两个是 已知的：Antp同源异型基因和Ubx基因本身。 一 连接的目标是确定这些的其他靶基因， 调节蛋白 顺式作用元件控制 Ubx的转录分布在40 kg区域（bxd区域） 位于基因的上游 这个控制区和Ubx基因 包括BX-C的三分之一，其剩余部分被 另外两个复杂基因（abdA和AbdB），每个基因都含有一个 家庭影院 该项目的另一个目标是定义 BXD控制区和另一个顺式- Ubx内含子中的调节区，调节Ubx转录， 特别是abdA和abdB编码的蛋白质， 如通过某些分段基因（例如，FTZ）和UBX本身， 调节这种顺式调节。 因此，越来越强调 调节蛋白质的方法。 的发展 合成和分离这些蛋白质的方法 果蝇宿主-载体表达系统，以及新的 确定其调节功能的技术，是进一步的 这个项目的目的。

The proposed research is directed toward solution of the problem of how genes dictate development in higher animals. Drosophila melanogaster is the preferred organism for attempting this solution because its genome is among the smallest and best defined, because more genes specifying development have been isolated, and because cloned DNAs can be easily inserted into its germ line. This grant focuses on the genetic regulatory functions of proteins encoded by the homeotic Ubx gene of the bithorax complex (BX-C) and on the regulation of this gene by the products of other genes. This gene provides the major determinants specifying the developmental pathoways for the identities of the metameres comprising the posterior half of the torax and the most anterior part of the abdomen (parasegments (ps) 5 and 6). The Ubx gene consists of a 78 kb transcription unit whose transcripts are differentially spliced to yield at least five mRNAs encoding a family of Ubx proteins characterized by constant N- and C-terminal regions and a variable central region lying just upstream from a homeo domain encoded by the conserved homeo box. One goal of the project is to define the mechanisms controlling his differential splicing. Another is to define the mechanisms by which each of these proteins binds to and regulates the expression of their target genes, two of which are known: the Antp homeotic gene and the Ubx gene itself. A connected goal is to define the other target genes of these regulatory proteins. Cis-acting elements controlling the transcription of Ubx are spread over a 40 kg region (bxd region) lying upstream of the gene. This control region and the Ubx gene comprise one third of the BX-C, whose remainder is occupied by two other complex genes (abdA and AbdB), each containing a homeo box. Another goal of this project is to define the mechanisms by which the bxd control region, and another cis- regulatory region in an intron of Ubx, regulate Ubx transcription, and particularly, how proteins encoded by abdA and abdB, as well as by certain segmentation genes (e.g., ftz) and by ubx itself, modulate this cis-regulation. There is thus an increasing emphasis on regulating proteins in this project. The development of methods for the synthesis and isolation of these proteins from Drosophila host-vector expression systems, and of novel techniques for determining their regulatory functions, is a further aim of this project.