Molecular genetic studies of asymmetric cell division in C.elegans

细胞不对称分裂是发育过程中产生细胞多样性的基本机制。在线虫中，许多细胞分裂的不对称性受Wnt信号通路的调节。我们关注的是胚胎后发育过程中T细胞的不对称分裂。我们筛选了破坏T细胞分裂不对称的突变体，并鉴定了101个突变体。我们已经使用SNP(单核苷酸多态)将这些突变定位在每个染色体上，并进行了互补测试。结果表明，它们是51个不同基因的突变，包括之前识别的那些基因。我们的结果表明，单个细胞的不对称分裂涉及大量的基因。我们克隆了一些我们已经鉴定的基因，并对它们的功能进行了分析。PSA-10和PSA-13编码SWL/SNF复合体的BAF25O和BAF53的同源物。CIC-1和CDK-8编码细胞周期蛋白C和CDK8的同源物，它们是转录调节复合体的组成部分。我们还发现，这些基因在不对称分裂后的子细胞中调节不对称基因的表达。我们还发现RMD-1编码一种新的具有多个卷曲结构域的蛋白质。RMD-1在哺乳动物中有多种同源基因，其功能尚未报道。对RMD-1胚胎功能的分析表明，RMD-1参与了线虫胚胎中许多基于微管的过程，如纺锤体定位、胞质分裂和细胞极性。

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.