Molecular genetic studies of asymmetric cell division in C.elegans

不对称细胞分裂是发育过程中产生细胞多样性的基本机制。在秀丽隐杆线虫中，许多细胞分裂的不对称性由Wnt信号通路调节。我们关注的是胚后发育过程中T细胞的不对称分裂。我们筛选了破坏T细胞分裂不对称性的突变体，并鉴定了101个突变体。我们使用SNP（单核苷酸多态性）在每条染色体上绘制了这些突变，并进行了互补试验。结果表明，它们是51个不同基因的突变，包括以前鉴定的那些。我们的研究结果表明，大量的基因参与了单细胞的不对称分裂。我们克隆了一些我们已经确定的基因，并分析了它们的功能。psa-10和psa-13编码BAF 250和BAF 53的同源物，BAF 250和BAF 53是SW 1/SNF复合物的组分。cic-1和cdk-8编码细胞周期蛋白C和CDK 8的同源物，细胞周期蛋白C和CDK 8是转录介体复合物的组分。我们还表明，这些基因调节不对称分裂后的子细胞中的不对称基因表达。我们还发现rmd-1编码一种具有多个卷曲螺旋结构域的新蛋白。RMD-1在哺乳动物中有多种同源物，其功能尚未报道。对rmd-1基因胚胎功能的分析表明，rmd-1基因在秀丽隐杆线虫胚胎中参与了纺锤体定向、胞质分裂和细胞极性等许多微管相关的过程。

Asymmetric cell division is a fundamental mechanism to produce cellular diversity during development. In C.elegans, asymmetries of many cell divisions are regulated by the Wnt signaling pathway. We are focusing on asymmetric division of the T cell during postembryonic development. We screened for mutants that disrupt asymmetry of the T cell division and identified 101 mutants. We have mapped these mutations on each chromosome using SNP (single nucleotide polymorphisms) and performed complementation tests. The results suggests that they are mutations of 51 different genes including those which was identified previously. Our results show that a large number of genes are involved in an asymmetric division of a single cell.We cloned some of the genes we have identified and analyzed their functions. psa-1O and psa-13 encodes homologs of BAF25O and BAF53 that are components of the SWl/SNF complex. cic-1 and cdk-8 encode a homolog of cyclin C and CDK8 that are components of the transcriptional Mediator complex. We have also shown that these genes regulate asymmetric gene expression in daughter cells after the asymmetric division. We also showed that rmd-1 encodes a novel protein with multiple coiled-coil domains. There are multiple homologs of RMD-1 in mammals whose functions have not been reported. Analyses of embryonic function of rmd-1 revealed that rmd-1 is involved in many microtubule-based processes, such as spindle orientation, cytokinesis and cell polarity in C.elegans embryo.