Program of the 2004 East Coast Worm Meeting - Caenorhabditis ...

11. Three conserved protein kinases, DYRK, CDC2 and GSK3 promote OMA-1 degradation
to establish proper cell fate and cell division polarity in early C. elegans embryos
Masaki Shirayama, Takao Ishidate, Kuniaki Nakamura, Craig C. Mello
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