Genes that influence LIN-12/Notch Activity in C. elegans

影响线虫 LIN-12/Notch 活性的基因

• 批准号: 7163547
• 负责人: Iva S Greenwald
• 金额: $ 17.5万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-22 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163547
• 关键词: Genes; influence; LIN; 12; Notch

LIN-12/Notch proteins are receptors that mediate cell-cell interactions that specify cell fate during animal development. Studies of LIN-12/Notch proteins are directly relevant to understanding the molecular mechanisms underlying two serious and common human diseases. Constitutive activation of LIN-12/Notch _roteins has been associated with the development of certain cancers in human patients and in mammalian models, and the activity of a key component of the LIN-12/Notch signal transduction pathway, presenUin, is central to the development of Alzheimer's disease. Other, less common, diseases have also been associated with aberrations in LIN-12/Notch pathway components. Our work on lin-12 in C. elegans has contributed to the current state of understanding of conserved developmental roles and molecular mechanisms of LIN-12/Notch proteins. This proposal is concerned with identifying and characterizing new genes that influence lin-12 activity in C. elegans. Our first specific aim encompasses new variations on a proven genetic screen, based on suppression of phenotypes associated with constitutive lin-12 activation [lin-12(d) alleles]. Our second specific aim is concerned with the basic characterization of new sel [suppressor/enhancer of lin-12] genes, and our third specific aim is concerned with understanding how the new genes we identify work together. The last two specific aims are involved with the LIN-12-mediated lateral signalling during vulval precursor cell specification. The fourth aim is concerned with identifying and characterizing the ligand for LIN-12 in this signalling event, and the fifth aim is concerned with characterizing a gene that may be involved in the interplay between Ras-mediated vulval induction and LIN-12-mediated lateral signalling. When these specific aims are completed, we hope to have identified conserved components and illuminated fundamental mechanisms of the regulation and execution of LIN-12/Notch signalling in animal development.

LIN-12/NOTCH蛋白是介导细胞 - 细胞相互作用的受体，这些相互作用指定细胞命运 动物发展。 LIN-12/NOTCH蛋白的研究与了解分子直接相关 两种严重和常见的人类疾病的机制。 LIN-12/Notch的组成型激活 _Rotein与人类患者和哺乳动物中某些癌症的发展有关 模型，以及LIN-12/Notch信号转导途径的关键成分的活性，Presenuin是 阿尔茨海默氏病发展的核心。其他不常见的疾病也已经关联 LIN-12/Notch途径组件中的畸变。 我们在秀丽隐杆线虫中对Lin-12的工作有助于当前对保守的理解状态 Lin-12/Notch蛋白的发育作用和分子机制。该提议与 识别和表征影响秀丽隐杆线虫中LIN-12活性的新基因。我们的第一个特定目标 基于对表型相关的表型的抑制，包括在验证的遗传筛查上的新变化 构成型LIN-12激活[Lin-12（d）等位基因]。我们的第二个特定目标与基本有关 新的SEL [lin-12]基因的抑制剂/增强子的表征，我们的第三个特定目的与 了解我们识别的新基因如何共同起作用。最后两个具体目标涉及 LIN-12介导的外阴前体细胞规范期间的侧向信号传导。第四目标是 在此信号事件中识别和表征LIN-12的配体，涉及第五目标 表征可能参与RAS介导的外阴诱导与 LIN-12介导的横向信号传导。 当这些特定目标完成后，我们希望已经确定了保守的组成部分和 动物中LIN-12/Notch信号的调节和执行的照明基本机制 发展。