GENETIC AND HORMONAL CONTROL OF NEURAL REORGANIZATION

多才多艺的实验生物黑腹果蝇是 提供了一个研究类固醇作用的模型系统 神经系统重组中的激素和基因表达 在变态过程中。在两种脊椎动物的神经系统中 和无脊椎动物，类固醇激素的作用导致 神经发生、细胞死亡和/或神经元结构的改变。 一般而言，类固醇激素被认为发挥了它们的作用。 通过在转录水平上改变基因表达。因此， 据推测，类固醇蜕皮激素蜕皮酮 策划果蝇中枢神经系统的变态并做到这一点 主要是通过改变神经系统中的基因表达。这个 为验证这一假说而提出的实验包括经典的 (突变)和分子遗传(基因克隆)方法，以及 既利用标准的组织学，也利用现代的 免疫组织化学技术。 最初，果蝇中枢神经系统的成熟是在 变形将在光镜水平上描述， 产生一个将在后续分析中使用的分期系统 突变体和体外中枢神经系统发育。中枢神经系统的依赖性 蜕皮酮的变态将通过检查 通过培养蜕皮激素缺乏的动物的中枢神经系统 使用和不使用激素的中枢神经系统。接下来，一个众所周知的角色 蜕皮激素诱导的调节基因座将通过以下方式评估 检查突变体和遗传马赛克中的中枢神经系统，并通过直接 用克隆的探针寻找蜕皮激素诱导的转录本 这个轨迹。一种昆虫特有的体内培养系统是 提出并将作为一种新的筛查方法进行测试 ITS的中枢神经系统可能需要发育突变 在变态过程中正常成熟。最后，给出了一个方案 概述了在中枢神经系统中分离蜕皮酮调控基因的方法。 基因组和cdna文库将通过差异和 消减-杂交方法以分离出 被荷尔蒙抑制或诱导。其中一种荷尔蒙- 可诱导基因的详细特征将通过确定其 发育和组织特异性以及DNA序列分析。 对人类神经疾病的竞争性理解，尤其是 那些有遗传基础的人，最终将需要 阐明神经的基本细胞和分子机制 发展。通过使用简单的 昆虫自然发生解体，激素介导的神经 系统重组，对人类神经疾病的洞察 可能会出现。

The versatile experimental organism Drosophila melanogaster is presented as a model system in which to study the role of steroid hormones and gene expression in nervous system reorganization during metamorphosis. In the nervous systems of both vertebrates and invertebrates, the action of steroid hormones results in neurogenesis, cell death, and/or changes in neuronal structure. In general, steroid hormones are believed to exert their effects by altering gene expression at the transcriptional level. Thus, it is hypothesized that the steroid molting hormone ecdysterone orchestrates Drosophila CNS metamorphosis and that it does so primarily by modifying gene expression in the nervous system. The proposed experiments to test this hypothesis include classical (mutational) and molecular genetic (gene cloning) approaches, and make use of both standard histological and as well as modern immunohistochemical techniques. Initially, the maturation of the Drosophila CNS during metamorphosis will be described at the light microscopic level, yielding a staging system which will be used in subsequent analyses of mutants and in vitro CNS development. The dependence of CNS metamorphosis on ecdysterone will be determined by examining the CNS in animals which are ecdysterone-deficient an by culturing the CNS with and without the hormone. Next, the role of a known ecdysterone-inducible regulatory locus will be evaluated by examining the CNS in mutants and genetic mosaics, and by a direct search for ecdysterone-induced transcripts using cloned probes from this locus. An in vivo culture system peculiar to insects is proposed and will be tested as a novel screening method for developmental mutants likely to be required in the CNS for its normal maturation during metamorphosis. Finally, a scheme is outlined for isolating genes regulated by ecdysterone in the CNS. Genomic and cDNA libraries will be screened by differential- and subtraction-hybridization methods in order to isolate genes which are repressed or induced by the hormone. One of the hormone- inducible genes will be characterized in detail, by determining its developmental and tissue specificity and by DNA sequence analysis. A compete understanding of human neurological disorders, especially those with hereditary bases, will ultimately require the elucidation of basic cellular and molecular mechanisms of neural development. By using the sophisticated genetics of a simple insect to unravel naturally occurring, hormone-mediated nervous system reorganization, insights into human neurological disorders may emerge.