ROLE OF A NOVEL PROTEIN IN THE WNT-1 SIGNALLING PATHWAY

一种新型蛋白质在 WNT-1 信号通路中的作用

• 批准号: 3081540
• 负责人: Jeffrey D. Axelrod
• 金额: $ 7.05万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081540
• 关键词: Drosophilidae; RNA directed DNA polymerase; SDS polyacrylamide gel electrophoresis; alleles; biological signal transduction; cell cell interaction; cellular polarity; confocal scanning microscopy; developmental genetics; gene expression; gene interaction; histogenesis; immunoprecipitation; in situ hybridization; messenger RNA; molecular cloning; nucleic acid sequence; polymerase chain reaction; protein sequence; protein structure function; protooncogene

Cell-cell signalling is a fundamental process in pattern development. The Drosophila segment polarity genes encode mediators of cell-cell signalling that function both during embryonic and imaginal development. One of these, wingless, encodes a secreted protein, homologous to the Wnt-1 protooncogene, that functions to determine cell fate in the developing fly. Mutations in the wingless signalling pathway that act during embryogenesis lead to alterations in the pattern of the embryonic segments, while mutations acting later in development affect a variety of adult structures. While the mechanism by which wingless signal transduction occurs is poorly understood, the dishevelled gene appears to play a key role in this process. In addition to mediating the wingless cell-cell signalling pathway, dishevelled is required for generation of the wild type tissue polarity manifested in the pattern of hairs and bristles on the adult cuticle. Control of tissue polarity also appears to involve a cell-cell signalling process. Therefore, dishevelled is important in two developmental pathways requiring cell- cell signalling, and serves as a paradigm for understanding the mechanisms by which cells communicate in developmental processes. In this proposal, I focus on experiments to elucidate the molecular mechanism by which dishevelled transduces intercellular signals in both the wingless and tissue polarity pathways, and to identify other gene products involved in these processes. My long range goals include developing an understanding of normal and abnormal developmental processes and their role in health and disease. I hope to continue in a career involving basic science research in an academic setting, and to maintain an interface with the practice of medicine both as a source for stimulation of research questions, and as a potential outlet for applications arising from the pursuit of those questions. I will be undertaking a postdoctoral fellowship during the course of this granting period in Dr. Norbert Perrimon's laboratory in the Department of Genetics at Harvard Medical School, which provides an ideal intellectual and physical environment in which to undertake these pursuits.

细胞间信号传导是模式发展的基本过程。 果蝇节段极性基因编码细胞间介质 在胚胎和图像发育过程中发挥作用的信号。 其中一个无翅，编码一种分泌蛋白，与 Wnt-1 原癌基因，其功能是决定细胞命运 发育中的苍蝇。 无翼信号通路中的突变 胚胎发生过程中会导致胚胎模式的改变 节段，而在发育后期起作用的突变会影响多种 成人结构。 而无翼信号的机制 对转导发生的了解知之甚少，出现凌乱的基因 并在此过程中发挥关键作用。 除了调解 wingless 细胞-细胞信号通路，需要蓬乱 野生型组织极性的产生表现在以下模式 成人角质层上的毛发和刚毛。 还控制组织极性 似乎涉及细胞间信号传导过程。 所以， 蓬乱在需要细胞的两种发育途径中很重要 细胞信号传导，并作为理解的范例 细胞在发育过程中进行交流的机制。 在 在这个建议中，我专注于通过实验来阐明分子机制 散乱的细胞间信号转导机制 无翅和组织极性途径，并识别其他基因 这些过程涉及的产品。 我的长期目标包括了解正常和 异常的发育过程及其在健康和疾病中的作用。 我希望继续从事基础科学研究的职业 学术环境，并与实践保持联系 医学既可以作为激发研究问题的来源，也可以作为 追求这些目标而产生的应用程序的潜在出口 问题。 我将在这期间进行博士后研究 诺伯特·佩里蒙 (Norbert Perrimon) 博士实验室的资助期间 哈佛医学院遗传学系，该系提供了 进行这些活动的理想智力和物质环境 的追求。