HAM-1蛋白调控线虫Q神经前体细胞不对称分裂机制研究

项目名称： HAM-1蛋白调控线虫Q神经前体细胞不对称分裂机制研究

项目编号： No.31201009

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 柴咏平

作者单位： 中国科学院生物物理研究所

项目金额： 23万元

中文摘要： 不对称细胞分裂产生两个命运不同的子细胞，是多细胞动物个体发育、成体组织维持及再生的细胞学基础，其异常可导致发育缺陷和重大疾病。在对线虫Q神经前体细胞的研究中，申请人所在课题组成员发现了一种全新且保守的基于肌球蛋白极性分布的不对称分裂机制，但其调控方式的研究相对空白。为此，申请人对线虫Q细胞发育进行正向遗传筛选及突变体遗传定位，发现了调控Q细胞不对称分裂的关键基因ham-1。ham-1编码功能未知的保守蛋白，序列分析带有DNA结合域。本项目将利用活体原位时序荧光成像技术，结合遗传学、生物化学和生物信息学等多种方法，揭示ham-1突变体中纺锤体排布和收缩环动态分布的异常，阐明ham-1基因的表达模式以及HAM-1蛋白的胞内定位，寻找其协同作用分子，深入理解HAM-1参与的Q细胞不对称分裂的调控分子网络。本课题的研究预期加深对神经发育等重要生物学过程的理解，为再生医学和相关疾病防治提供科学启示。

中文关键词： 秀丽隐杆线虫；不对称细胞分裂；转录因子；细胞骨架；

英文摘要： Asymmetric cell divisions generate two daughter cells of distinct fates and are essential for organismal development, adult tissues maintenance and regeneration. Abnormal ACDs cause severe developmental defects and diseases. Recent research in the C. elegans Q neuroblast reported a novel myosin II polarization-based mechanism for asymmetric cell division, but the underlying mechanism remains elusive. We have thus performed a forward genetic screen to isolate mutations defective in Q cell asymmetric division. By genetic mapping and gene cloning, we obtained two mutant alleles of ham-1 gene that causes abnormal Q cell division. The gene ham-1 encodes a conserved protein with unknown function, and sequence alignment reveals a DNA binding domain. Our proposed research aims to understand the function of ham-1 in asymmetric cell division. We will combine fluorescence time-lapse imaging with genetic, biochemical and bioinformatics approaches to study spindle position and contractile ring dynamics during asymmetric division in ham-1 mutant, to study ham-1 expression pattern and protein localization, to isolate binding partners of HAM-1 protein and to construct the HAM-1 based regulatory network of Q cell asymmetric division. We expected that our research will advance our understanding of asymmetric cell division and neu

英文关键词： C. elegans；asymmetric cell division；transcriptional factor；cytoskeleton；