MOLECULAR BASIS FOR GENETIC CONTROL OF DEVELOPMENT

提出的研究旨在解决这个问题。 基因如何决定高等动物的发育。果蝇 黑腹鱼是尝试这一点的首选生物。 因为它的基因组是最小和最好的之一 定义，因为更多指定发育的基因已经被定义 因为克隆的DNA可以很容易地插入到其 生殖系。这项拨款的重点是基因调控功能。 由双胸腺的同源异型Ubx基因编码的蛋白质 复合体(BX-C)及其产物对该基因的调控 其他基因的基因。这个基因提供了主要的决定因素 为这些人的身份指定发展途径 由Torax的后半部分和Toax的 腹部最前部(副节段(PS)5和6)。 Ubx基因由一个78kb的转录单位组成，其 转录本被差异剪接以产生至少5个mRNA 编码一个Ubx蛋白家族，其特征是恒定的N- 以及C-末端区域和位于 由保守的Homeo编码的Homeo结构域的上游 盒。该项目的一个目标是定义机制 控制他的差异拼接。另一种方法是定义 这些蛋白质中的每一种与和的结合机制 调节它们的目标基因的表达，其中两个是 已知：ANTP同源异型基因和Ubx基因本身。一个 相关的目标是定义这些基因的其他靶基因 调节蛋白。顺式作用元件控制着 Ubx的转录分布在40千克的区域(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，其余部分由 另外两个复杂基因(Abda和AbdB)，每个都包含一个 Homeo盒子。此项目的另一个目标是定义 BxD控制区和另一个顺- Ubx内含子中的调节区，调节Ubx转录， 尤其是abda和abdB所编码的蛋白质 如通过某些分段基因(例如，FTZ)和UBX本身， 调节这一顺式调控。因此，越来越多的人强调 关于调节这个项目中的蛋白质。的发展。 这些蛋白质的合成和分离方法 果蝇宿主载体表达系统及其新的研究进展 用于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.