2004 East Coast Worm Meeting abstract 11
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UMass Medical School, Worcester, MA 01605
The proper establishment of cell polarity and identity underlies development in all multicellular animals. In C. elegans, the 4-cell stage blastomere, EMS receives inductive signals that orient its division axis and specify the endoderm fate. GSK-3 is positively required for Wnt-mediated EMS cell fate determination and mitotic spindle alignment in EMS. Paradoxically, despite lacking E-derived endoderm, gsk-3 mutants frequently produce ectopic endoderm from the C blastomere. Thus GSK-3 functions to promote endoderm development in E and simultaneously functions to repress endoderm development in C. In our screens for temperature-sensitive mutants, we isolated 5 mutants that (like gsk-3 mutants) produce ectopic endoderm derived from the C blastomere and are defective in EMS cell polarity. These mutations include one allele of cdk-1, one allele of its binding partner, cks-1, one allele of the dyrk-family kinase member mbk-2, and two alleles of the zinc finger gene oma-1. Previous work has linked OMA-1 destruction to C-cell fate specification and EMS polarity1), therefore, we tested whether cdk-1, mbk-2 and gsk-3 mutants exhibit defects in OMA-1 degradation. We found that OMA-1 protein persists ectopically in all of these mutants. We have also found that MBK-2 directly phosphorylates OMA-1 protein and this phosphorylation is abolished in the ne411and zu405 OMA-1 mutant protein due to a mutation in a consensus MBK-2 site. We are currently testing the model that sequential phosphorylation of OMA-1 by MBK-2, CDK-1 and GSK-3 kinases is required for the timely degradation of OMA-1 protein.
1) Lin, R. Dev. Biol. 258 (2003) 226