Regulation of Sex Specific Genes in Drosophila

果蝇性别特异性基因的调控

• 批准号: 6688141
• 负责人: THOMAS W CLINE
• 金额: $ 59.65万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6688141
• 关键词: Drosophilidae; Ehrlichia; cell cell interaction; developmental genetics; gene dosage; gene expression; gene interaction; genetic models; genetic regulatory element; germ cells; host organism interaction; in situ hybridization; intracellular parasitism; microarray technology; regulatory gene; sex chromosomes; sex determination

DESCRIPTION (provided by applicant): Molecular genetic analysis of Drosophila development has shown the complexity, diversity, and relatedness of developmental mechanisms in higher organisms. By revealing the kinds of phenomena that underlie human development, study of this model organism provides invaluable insights for improving human health. The following proposal is based on the understanding and genetic tools developed over years of study of the gene Sex-lethal (Sxl), the master regulator of Drosophila sex determination and X-chromosome dosage compensation. The proposal is designed not only to extend specific knowledge of sex determination and dosage compensation, but also to expand our general understanding of the relationship between gene regulation in germ cells and that in somatic cells, the molecular nature of host-parasite interactions in arthropods, the control of behavior by genes, and the unique character of extremely early expressed genes that allows them to be expressed when nearly all other genes are silent. All the experiments proposed rely heavily on the enormous power of forward genetics in this model system. There are three general aims in this proposal, all involving Sxl and all designed to synergize. First, an understanding is sought of how and why Sxl functions in germ cells and how the obligate intracellular parasitic bacterium Wolbachia pipientis interacts with it in that cell type. Wolbachia is a ubiquitous arthropod parasite with health relevance (in River Blindness) that is notorious for manipulating the reproductive biology of its hosts. It may be an important factor driving evolution. This parasite has not previously been amenable to study in a model genetic system like Drosophila melanogaster. The germline functioning of Sxl differs remarkably from its functioning in the soma, which is better understood. The germline studies proposed are relevant to the mechanism of meiosis, stem-cell behavior, cell-cell signaling, gene mutation, and pleiotropy. Second, experiments are proposed to understand a newly discovered branch in the somatic sex-determination gene hierarchy that controls an important aspect of female behavior, namely egg-laying. Finally, studies of the set of genes that act additively to generate the primary sex-determination signal in the fly will be continued to understand how these genes are expressed so much earlier than other genes and whether they are as unique as they seem in this regard.

描述（由申请人提供）：果蝇发育的分子遗传学分析显示了高等生物体发育机制的复杂性、多样性和相关性。通过揭示人类发展背后的各种现象，对这种模式生物的研究为改善人类健康提供了宝贵的见解。以下建议基于对性致死基因（Sxl）多年研究的理解和开发的遗传工具，该基因是果蝇性别决定和 X 染色体剂量补偿的主要调节因子。该提案的目的不仅是为了扩展性别决定和剂量补偿的具体知识，而且还为了扩展我们对生殖细胞和体细胞基因调控之间关系、节肢动物宿主-寄生虫相互作用的分子性质的一般理解，基因对行为的控制，以及极早期表达基因的独特特征，使得它们能够在几乎所有其他基因沉默时表达。所有提出的实验都严重依赖于该模型系统中正向遗传学的巨大力量。该提案有三个总体目标，全部涉及 Sxl，并且全部旨在协同作用。首先，寻求了解 Sxl 在生殖细胞中如何以及为何发挥作用，以及专性细胞内寄生细菌 Wolbachia pipientis 如何在该细胞类型中与其相互作用。沃尔巴克氏体是一种普遍存在的与健康相关的节肢动物寄生虫（在河盲症中），它因操纵宿主的生殖生物学而臭名昭著。这可能是推动进化的重要因素。这种寄生虫以前不适合在像果蝇这样的模型遗传系统中进行研究。 Sxl 的种系功能与其在体细胞中的功能显着不同，后者是我们更好理解的。提出的种系研究与减数分裂机制、干细胞行为、细胞间信号传导、基因突变和多效性相关。其次，提出了实验来了解体细胞性别决定基因层次结构中新发现的一个分支，该分支控制着女性行为的一个重要方面，即产卵。最后，将继续对在果蝇中产生主要性别决定信号的一组基因进行研究，以了解这些基因如何比其他基因更早地表达，以及它们在这方面是否像看起来那样独特。 。