MOLECULAR BASIS FOR GENETIC CONTROL OF DEVELOPMENT

基因如何决定高等生物的发育， 现代生物学中最重要和最吸引人的。 拟议研究 是为了解决这个问题。 果蝇 是尝试这种解决方案的首选生物体，首先是因为它 在高等真核生物中，小基因组是定义最好的，其次是因为 选择发育途径的基因最好在 果蝇，最后是因为最近发展的一个系统， 通过克隆DNA进行的行转换提供了一个特殊的工具， 基因功能分析。 我们通过以下方式利用这些优势 两个基因系统 (1)双胸复合体由一组基因组成 这些细胞在早期选择通向胸部的发育途径， 和腹部 我们已经分离了200 kb的克隆DNA， 双胸复合体，构建了一个突变的分子图谱， 它的几个基因，并确定了几个RNA转录从这些 基因. 进一步定义复合体的实验计划是 分为两部分。 一个是针对进一步的表征 复合物的基因产物，它们在动物体内的分布， 不同的发展时期，以及它们在这些时期的作用， 另一个是确定这些规则， 调节因子--复合体的基因是如何被调节的， 不同的基因在不同的创始细胞中表达。 (2)第二 系统由监管层次结构组成，这些层次结构由 类固醇激素蜕皮激素开始变态成成虫。 我们有 最近，科学家们分离出了六个“早期”基因中的一个， 在幼虫唾液腺的层次结构中， 对荷尔蒙的反应。 奇怪的是，这种基因是由荷尔蒙诱导的， 几个幼虫和成虫组织，表明层次结构 不同组织的特异性具有重叠的上等级。 在这里， 实验计划分为两部分：一部分是在 确定类固醇激素诱导的机制 早期基因的表达，另一个决定了性质， 早期基因产物在不同层次中的功能。

The problem of how genes dictate development of higher organisms is perhaps the most important and appealing in modern biology. The proposed research is directed toward the solution of that problem. Drosophila melanogaster is the preferred organism for attempting this solution, first because its small genome is, among higher eukaryotes, the best defined, second because the genes that select developmental pathways are best defined in Drosophila, and finally because the recent development of a system for germ line transformation by cloned DNAs provides an exceptional tool for the analysis of gene function. We exploit these advantages with the following two gene systems. (1) The bithorax complex consists of a cluster of genes that act early to select the developmental pathways leading to the thoracic and abdominal segment. We have isolated 200kb of cloned DNA from the bithorax complex, constructed a molecular map of the mutations that define several of its genes, and identified several RNAs transcribed from those genes. The experimental plan for the further definition of the complex is divided into two parts. One is directed toward a further characterization of the gene products of the complex, their distribution in the animal at different times of development, and their function at these times and places; and the other consists in determining the regulation of these regulators--how the genes of the complex are themselves regulated so that different genes are expressed in different founder cells. (2) The second system consists of the regulatory hierarchies that are triggered by the steriod hormone ecdysone to initiate metamorphosis to the adult. We have recently isolated one of the half-dozen "early" genes that act at the top of the hierarchy in the larval salivary gland and which exhibit a primary response to the hormone. Curiously, this gene is induced by the hormone in several larval and imaginal tissues, indicating that the hierarchies specific to different tissues have overlapping upper ranks. Here again, the experimental plan is divided into two parts: One consisting in the determination of the mechanism by which the steroid hormone induces expression of the early genes, and the other of determining the nature and function of the early gene products in the different hierarchies.