FUNCTION OF THE GLI GENES IN SONIC SIGNALING

Sonic Hedgehog是诱导小鼠腹侧细胞类型所必需的 神经管，并在最近几年取得了快速的进展 了解音速刺猬的信号通路。vbl.使用 非洲爪哇作为典范，主要调查者小组有 显示编码锌指转录因子的Gli基因 在神经板或神经管中瞬时和分级表达， 都参与了这一过程。具体地说，Gli1被发现是 底板和腹侧神经元的充要条件 分化，而Gli2和Gli3似乎拮抗这种作用 Gli1.在进一步研究Gli基因在声波刺猬中的作用中 主要研究者神经管的信号与发育 提出了几项重要而雄心勃勃的研究。他提议 分析Gli1基因产物的组织和细胞定位， 使用Site-Site进行Gli蛋白的结构/功能分析 定向突变，使Gli1或Gli3转基因小鼠成为天然的 青蛙研究的延伸，进一步分析拮抗Gli1 功能，并最终确定Gli3是否需要 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.