FUNCTION OF THE GLI GENES IN SONIC HEDGEHOG SIGNALING

声刺猬是诱导腹侧细胞类型所必需的 神经管，近年来取得了快速进展 了解音速刺猬的信号通路。 使用 首席研究员小组以非洲爪蟾为模型 表明编码锌指转录因子的 Gli 基因 在神经板或神经管中具有瞬时和分级表达， 都参与到这个过程中。 具体来说，Gli1被发现是 底板和腹侧神经元的必要和充分 分化，而 Gli2 和 Gli3 似乎拮抗这种作用 的Gli1。 进一步研究 Gli 基因在音刺猬中的作用 神经管信号传导和发育，首席研究员 提出了几项重要且雄心勃勃的研究。 他提议 分析 Gli1 基因产物的组织和细胞定位， 使用位点进行 gli 蛋白的结构/功能分析 定向诱变，使 Gli1 或 Gli3 转基因小鼠成为天然小鼠 青蛙研究的延伸，进一步分析拮抗Gli1 青蛙中的功能，最后确定是否需要 Gli3 背神经管细胞测定。

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.