WRM1 Function in Polarity Establishment C.elegans

描述（由申请人提供） 不对称的细胞分裂导致子细胞的大小和命运不同 并且对于蜂窝分集的适当规范是关键的。然而，在这方面， 这些进化保守过程背后的分子机制是 大部分未知。利用感应信号通路 极化C.线虫胚胎作为实验系统， 描述细胞极化背后的分子机制的模型将是 测试.该模型将细胞命运决定和纺锤体重定向联系起来 β-连环蛋白癌基因同源物WRM-1的功能，根据 协调细胞周期和Wnt/Wg以及SRC相关通路的调节。 将检查通过CDK-1介导的磷酸化的WRM-1调节， 预测WRM-1定位的变化。WRM-1的改造也被预测 影响WRM-1蛋白结合特性，并将在 定向和偏倚蛋白质相互作用测定。最后，新的筛选 将采用方法学鉴定温度敏感的WRM-1等位基因 和参与细胞极化的新基因。阐明 细胞多样性产生背后的机制回答了基本的生物学 问题，并可能提供新的见解致癌。

DESCRIPTION (provided by applicant) Asymmetric cell divisions result in daughter cells differing in size and fate and are critical for the proper specification of cellular diversity. However, the molecular mechanisms behind these evolutionarily conserved processes are largely unknown. Using the inductive signaling pathways responsible for polarizing the EMS blastomere in C. elegans embryos as an experimental system, a model describing the molecular mechanisms behind cell polarization will be tested. This model links both cell fate determination and spindle reorientation to the function of the Beta-catenin oncogene homolog WRM-1, under the coordinate regulation of the cell cycle and Wnt/Wg and SRC-related pathways. WRM-l regulation by CDK-1-mediated phosphorylation will be examined for predicted changes in WRM-1 localization. WRM-1 modification is also predicted to affect WRM-1 protein-binding characteristics and will be examined in directed and biased protein interaction assays. Finally, new screening methodologies will be employed to identify temperature-sensitive wrm-1 alleles and novel genes involved in cellular polarization. Elucidation of the mechanisms behind the generation of cellular diversity answers basic biological questions and may provide new insight into carcinogenesis.