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代细胞的大小和命运不同 对于细胞多样性的适当规范是至关重要的。然而， 这些进化上保守的过程背后的分子机制是 很大程度上是未知的。使用感应信号通路负责 将线虫胚胎中的EMS卵裂球极化作为实验系统， 描述细胞极化背后的分子机制的模型将是 测试过。该模型将细胞命运决定和纺锤体重定向联系在一起 对β-连环蛋白癌基因同源基因WRM-1的功能的影响 协调细胞周期和Wnt/Wg及SRC相关通路的调节。 将研究CDK-1介导的磷酸化对WRm-L的调节 预测了WRM-1本地化的变化。还预测了WRM-1的修饰 影响WRM-1蛋白结合特性，将在 定向和偏向蛋白质相互作用分析。最后，新的筛选 将采用方法学来识别对温度敏感的WRM-1等位基因 以及与细胞极化有关的新基因。澄清： 细胞多样性产生背后的机制回答了基本的生物学问题 问题，并可能为癌症的发生提供新的见解。

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.