MOLECULAR BASIS FOR GENETIC CONTROL OF DEVELOPMENT

基因如何决定高等生物体的发育，这个问题可能是 现代生物学中最重要和最吸引人的。拟议的研究 就是为了解决这个问题。黑腹果蝇 是尝试这种解决方案的首选有机体，首先是因为它的 在高等真核生物中，小基因组是定义最好的，其次是 选择发育途径的基因最好定义在 果蝇，最后是因为最近一种细菌系统的发展 通过克隆的DNA进行的线转换为 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 及早选择通向胸腔的发育途径 还有腹部部分。我们已经提取了200kb的克隆DNA。 双胸复合体，构建了一张突变的分子图谱 它的几个基因，并鉴定了从这些基因转录的几个RNA 基因。进一步定义该复合体的实验计划是 分为两部分。一种是针对进一步的描述 在复合体的基因产物中，它们在动物体内的分布是 不同的发展时期，以及它们在这些时代和 地方；另一个在于确定对这些地方的监管 调节者--复合体的基因本身是如何被调控的，以便 不同的创始细胞表达不同的基因。(2)第二个 系统由监管层次结构组成，由 类固醇激素蜕皮激素启动向成年变态。我们有 最近分离了六个在顶端起作用的“早期”基因中的一个 在幼虫唾液腺中的层级，表现出初级的 对荷尔蒙的反应。奇怪的是，这个基因是由荷尔蒙诱导的 几个幼虫和成虫组织，表明 针对不同的组织有重叠的上层。又来了， 实验计划分为两部分：一是 类固醇激素诱导机制的测定 一是早期基因的表达，二是决定基因的性质和性质 早期基因产物在不同层级中的功能。

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.