NEMATODE SEX DETERMINATION

线虫性别决定

• 批准号: 2175876
• 负责人: BARBARA J MEYER
• 金额: $ 29.74万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2175876
• 关键词: Caenorhabditis elegans; Drosophilidae; autoradiography; autosome; biological signal transduction; cell cell interaction; complementary DNA; cytogenetics; developmental genetics; endonuclease; fluorescence microscopy; gene complementation; gene dosage; gene expression; genetic regulation; genetic transcription; hermaphroditism; lethal genes; male; meiosis; molecular cloning; nondisjunction; nucleic acid hybridization; nucleic acid sequence; sex chromosomes; sex determination

Our long-term goals are two-fold, (1) to understand, in genetic and molecular terms, the basis for the male/hermaphrodite decision in the nematode C. elegans and (2) to understand the mechanism of X chromosome dosage compensation at the genetic and molecular levels. The primary sex-determining signal in C. elegans is the X/A ratio; 2X/2A animals are hermaphrodite, and IX/2A animals are male. How the primary sex-determining signal is assessed and subsequently translated into the choice of either the hermaphrodite or male mode of sexual development re- mains a mystery, but is a primary focus of this grant. We have acquired significant insight into understanding the basis of the male/hermaphrodite decision by demonstrating that the sex determination and dosage compensation processes share common early steps prior to their divergence into two separate pathways. The hermaphrodite mode is coordinately controlled by at least two genes, sdc-I and sdc-2; the male mode is controlled by xol-l. The sdc genes appear to play a role in either assessing the X/A ratio or transmitting this signal to both the sex determination and dosage compensation pathways. Genetic interactions suggest that xol-l is the earliest acting gene in the known hierarchy that controls the male/hermaphrodite decision and is likely to be the gene nearest to the primary sex-determining signal. A fourth gene, dpy,-29, is also involved in controlling both processes, and illustrates a paradoxical feedback between dosage compensation disruptions and sex determination. Further insight into the male/hermaphrodite decision will be sought by: (1) Identification and analysis of additional genes central to both sex determination and dosage compensation. (2) A mosaic analysis of sdc-2, xol-l and dpy-29 to determine when the sex determination decision is made and whether it is a cell autonomous process or whether it involves factors extrinsic to the cell, such as diffusible products or cell-cell interactions. (3) An extensive molecular analysis of the genes that play a central role in the male/hermaphrodite decision, sdc-1, sdc-2, xol-l and dpy-29. The molecular analysis will include discerning how these genes are regulated in response to the X/A signal, (or how they help assess the X/A ratio), as well as how they regulate each other and the downstream sex determination and dosage compensation genes. The molecular characterization of these early-acting components of the sex determination decision will be the first molecular analysis of genes that control both processes in this organism. Further insight into the mechanism of X chromosome dosage compensation will be sought by: (1) Identification and analysis of additional dosage compensation genes. (2) Molecular characterization of two genes critical to the process, dpy-27 and dpy-28. This represents the first molecular characterization of dosage compensation genes in this organism. Elucidating the mechanism of sex determination will provide fundamental insight into developmental processes that go awry in human diseases.

我们的长期目标是两个方面，（1）在遗传和 分子术语，是男性/雌雄同体决定的基础 线虫C.秀丽隐杆线虫和（2）了解X染色体的机理 遗传和分子水平的剂量补偿。 秀丽隐杆线虫中的主要性别确定信号是X/A比。 2x/2a 动物是雌雄同体，ix/2a动物是雄性。主要是如何的 评估性别确定的信号，然后转化为 选择雌雄同体或男性性发展方式的选择 主谜，但是这笔赠款的主要重点。我们已经获得了 对理解男性/雌雄同体的基础的重大见解 通过证明性别确定和剂量来决定 薪酬流程在发散之前共享共同的早期步骤 进入两个单独的途径。雌雄同体模式是协调的 由至少两个基因控制SDC-I和SDC-2；男性模式是 由XOL-L控制。 SDC基因似乎在任何一个中起作用 评估X/A比或将此信号传输到性别 确定和剂量补偿途径。遗传相互作用 建议XOL-L是已知层次结构中最早的表演基因 控制男性/雌雄同体的决定，可能是基因 最接近初级性别确定信号。第四个基因，dpy，-29，是 还参与控制这两个过程，并说明了一个矛盾的 剂量补偿中断与性别确定之间的反馈。 对男性/雌雄同体的决定的进一步见解将由以下方式寻求：（1） 识别和分析两种性别中心的其他基因 确定和剂量补偿。 （2）SDC-2的镶嵌分析， XOL-L和DPY-29确定何时做出性别决定 以及它是单元自主过程还是涉及因素 细胞外的外部，例如扩散产物或细胞细胞 互动。 （3）对发挥作用的基因进行广泛的分子分析 在男性/雌雄同体决定中的中心作用，SDC-1，SDC-2，XOL-L和 DPY-29。分子分析将包括辨别这些基因的方式 根据X/A信号的响应（或它们如何帮助评估X/A） 比例），以及他们如何相互调节和下游性别 确定和剂量补偿基因。分子表征 性别确定决定的这些早期作用组成部分将是 控制这两个过程的基因的第一个分子分析 生物。 进一步了解X染色体剂量补偿机理 通过：（1）识别和分析其他剂量 补偿基因。 （2）两个与至关重要的基因的分子表征 该过程，DPY-27和DPY-28。这代表了第一个分子 该生物体中剂量补偿基因的表征。 阐明性别确定的机制将提供基本 深入了解人类疾病出现问题的发展过程。