EARLY STEPS IN DROSOPHILA SEX DETERMINATION

果蝇性别决定的早期步骤

• 批准号: 3306879
• 负责人: LESLIE R BELL
• 金额: $ 17.14万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3306879
• 关键词: DNA binding protein; DNA footprinting; Drosophilidae; RNA splicing; alleles; binding proteins; developmental genetics; early embryonic stage; gene complementation; gene dosage; genetic enhancer element; genetic mapping; genetic transcription; regulatory gene; sex chromosomes; sex determination; suppressor mutations; transcription factor

The goal of this research is a molecular understanding of the early steps of the Drosophila sex determination pathway as an example of an experimentally tractable developmental switch. The focus is the regulatory gene Sex-lethal, which functions at the start of a short hierarchy of genes that are regulated by sex-specific, alternative RNA splicing. Sxl produces transcripts that are spliced into a functional form in females but a non-functional form in males. Sxl is the first identified gene after the initial pathway signal, the ratio of X chromosomes to autosomes. Sxl's early response is characterized by a set of female-specific transcripts observed transiently in early embryogenesis; these are distinct from the later transcripts regulated by splicing. Regulatory genes that control this early step will be identified and characterized in order to elucidate the mechanism capable of distinguishing between one and two X chromosomes. The approach will be to devise genetic screens for suppressors of existing signal element mutations, and to screen for proteins that bind enhancers of the Sxl early promoter. Interactions between regulatory proteins and with DNA will be examined. The relevance of Drosophila to human development has been well established with the description of homeobox genes and their pattern of expression in mammalian embryos. Definition of a genetic switch such as Drosophila sex determination may likewise be expected to provide a model for human regulatory mechanisms in development.

这项研究的目标是从分子上了解早期的 果蝇性别决定途径的步骤， 一种实验上易于控制的发展开关 重点是 调节基因性致死，其功能在一个短的开始 由性别特异性、替代性、 RNA剪接。 Sxl产生的转录本被拼接成一个 女性的功能性形式，但男性的非功能性形式。 SXL 是在初始途径信号之后第一个被识别的基因， X染色体与常染色体的比例。 SXL的早期反应是 其特征在于观察到一组女性特异性转录物， 在早期胚胎发生中短暂;这些与 后期转录受剪接调控。 调节基因， 控制这一早期步骤将被识别和表征， 为了阐明能够区分 一条和两条X染色体 方法将是设计基因 筛选现有信号元件突变的抑制子，和 为了筛选能在Sxl早期结合增强子的蛋白质， 启动子 调节蛋白之间的相互作用以及与DNA的相互作用 将被审查。 果蝇与人类发展的相关性一直很好 通过描述同源异型盒基因及其 哺乳动物胚胎中的表达模式。 定义 基因开关，如果蝇性别决定， 有望为人类的调节机制提供一个模型， 发展