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.
