线虫性腺前体细胞Z1和Z4不对称分裂的分子细胞学机制研究

Asymmetric cell division (ACD) of somatic gonad precursor cells, Z1 and Z4 generates cellular diversity and defines the shape and polarity during gonadogenesis. Several unique features regarding the regulatory molecules and daughter cell fate determination make Z1/Z4 a useful system to study postembeyonic ACDs. However, the lacking of the efficient visualization tool has been the main obstacle towards understanding this fundamental process at subcellular structure level. In this study, we developed a time-lapse imaging technique to visualize the dynamics of subcellular machineries such as contractile ring, spindle and polarized molecules during Z1/Z4 ACD; such resolution has never been achieved in our knowledge. In the molecular level, POP-1, a conserved transcriptional factor responding to Wnt signal has been shown to play the roles in regulating the 1st round asymmetric cell division. We will utilize the imaging technique combined with genetic and biochemical approaches to search the polarized molecules involved in Z1/Z4 ACD regulation, to screen the Wnt signals that responsible for POP-1's localization and function, to find out POP-1's target genes, and finally to draw a more complete picture of the regulatory pathway. Our aim is to illuminate the underlying machinery of Z1/Z4 ACD in subcellular level, and to construct the POP-1 contained regulatory network of Z1/Z4 asymmetric cell division. We expected that our research will provide an advanced insight into the understanding on asymmetric cell division mechanism, somatic gonad development and on human diseases.

线虫性腺前体细胞Z1/Z4的不对称分裂为性腺发育提供细胞多样性，是性腺发育的基础。该过程具有很多独特之处，如第一轮分裂雌雄同体和雄虫中子细胞大小迥异，第二轮分裂中细胞极性轴发生旋转等，因此其调控机制值得深入研究。本课题拟建立高分辨率活体成像技术，突破长久以来技术上的局限，深入观察Z1/Z4不对称分裂中亚细胞结构如收缩环、纺锤体的动态行为，寻找其分裂不对称性的细胞生物学机理。在分子调控层面上，我们将结合显微成像技术、遗传、生化等手段检测已知经典极性分子如PAR复合物等在Z1/Z4的表达与分布；以已知调节Z1/Z4不对称分裂的Wnt下游转录因子POP-1为突破口，筛选上游Wnt通路信号分子及POP-1的效应因子。本课题旨在亚细胞水平上刻画Z1/Z4不对称分裂的过程，探究其分子生物学调控机制，以期加深对不对称分裂这一基本生物学过程的理解，为性腺发育和相关疾病防治提供科学启示。

线虫性腺前体细胞Z1/Z4 的不对称分裂为性腺发育提供细胞多样性，是性腺发育的基础。该过程具有很多独特之处，如第一轮分裂雌雄同体和雄虫中子细胞大小迥异，第二轮分裂中细胞极性轴发生旋转等，因此其调控机制值得深入研究。本课题拟建立高分辨率活体成像技术，突破长久以来技术上的局限，深入观察Z1/Z4 不对称分裂中亚细胞结构如收缩环、纺锤体的动态行为，寻找其分裂不对称性的细胞生物学机理。在分子调控层面上，我们将结合显微成像技术、遗传、生化等手段检测已知经典极性分子如PAR 复合物等在Z1/Z4的表达与分布；以已知调节Z1/Z4 不对称分裂的Wnt 下游转录因子POP-1 为突破口，筛选上游Wnt 通路信号分子及POP-1 的效应因子。本课题旨在亚细胞水平上刻画Z1/Z4 不对称分裂的过程，探究其分子生物学调控机制，以期加深对不对称分裂这一基本生物学过程的理解，为性腺发育和相关疾病防治提供科学启示。