FUNCTION OF THE GLI GENES IN SONIC SIGNALING

GLI 基因在声波信号传导中的功能

• 批准号: 6539971
• 负责人: Ariel Ruiz i Altaba
• 金额: $ 27.91万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-20 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6539971
• 关键词: Xenopus; biological signal transduction; biomarker; cell cell interaction; cell type; gene expression; genetically modified animals; histogenesis; laboratory mouse; neural plate /tube; neurogenesis; neurons; posttranslational modifications; protein structure function; site directed mutagenesis; transcription factor

Sonic hedgehog is required for the induction of ventral cell types in the neural tube, and in recent years for rapid progress has been made in understanding the signaling pathway for sonic hedgehog. Using Xenopus laevis as a model, the Principal Investigator's groups has shown that Gli genes, which encode zinc finger transcription factors with transient and graded expression in the neural plate or neural tube, are involved in this process. Specifically, Gli1 has been found to be necessary and sufficient for floor plate and ventral neuronal differentiation, whereas Gli2 and Gli3 appear to antagonize the effect of Gli1. In further studies of the roles of Gli genes in sonic hedgehog signaling and development of the neural tube, the Principal Investigator proposes several important and ambitious studies. He proposed to analyze the tissue and cellular localization of the Gli1 gene products, to carry out a structure/function analysis of gli proteins using site- directed mutagenesis, to make Gli1 or Gli3 transgenic mice as a natural extension of the frog studies, to further analyze the antagonize Gli1 function in the frogs, and finally to determine if Gli3 is required for dorsal neural tube cell determination.

Sonic hedgehog是诱导腹侧细胞类型所必需的， 神经管，近年来取得了迅速的进展 在理解音刺猬的信号通路方面。 使用 以非洲爪蟾为模型，首席研究员的小组已经 显示编码锌指转录因子的Gli基因 在神经板或神经管中有瞬时和分级表达， 参与了这个过程。 具体来说，Gli 1被发现是 底板和腹侧神经元 分化，而Gli 2和Gli 3似乎拮抗这种作用 关于Gli 1 为了进一步研究Gli基因在音刺猬中的作用， 信号和神经管的发展，首席研究员 提出了几项重要而雄心勃勃的研究。 他提议 分析Gli 1基因产物的组织和细胞定位， 使用位点- 定向诱变，使Gli 1或Gli 3转基因小鼠作为天然的 青蛙研究的扩展，以进一步分析拮抗Gli 1 功能，并最终确定是否需要Gli 3 背神经管细胞测定