During C. elegans embryogenesis, a four cell stage blastomere called P2 uses Wnt signaling to induce anterior-posterior polarity in its sister blastomere EMS. In embryos defective for the function of Wnt pathway components the posterior EMS daughter E, which normally produces endoderm, develops like its anterior sister MS. We have previously reported the characterization of a C. elegans GSK-3 homolog called
sgg-11, which shares this phenotype suggesting that
sgg-1 acts positively with the Wnt pathway to regulate a-p polarity in EMS. This was somewhat surprising because in other systems, GSK-3 functions to repress Wnt pathway outputs and is negatively regulated by Wnt signaling to relieve this repression. We also reported that
sgg-1 mutant embryos produce an ectopic E-like cell that is derived from C, a daughter of P2. Further analysis has shown that the source of this ectopic endoderm is Cp, the posterior daughter of C. Double mutant analysis shows that Wnt pathway components also are required for the production of Cp-derived endoderm in
sgg-1 embryos. This result suggests that Wnt signaling functions to make Cp different from Ca and that
sgg-1 is required in Cp to prevent it from adopting an E-like fate. Furthermore,
sgg-1 synergizes with the Wnt pathway in EMS indicating that
sgg-1 and the Wnt pathway have some non-overlapping functions. Rather than functioning with the Wnt pathway during polarity induction, perhaps
sgg-1 functions at the level of blastomere identity to make Cp and E, or perhaps EMS and C, different from each other. Like the Wnt pathway,
sgg-1 is required for the orientation of the mitotic spindle in EMS1 suggesting an overlap with the Wnt pathway during induced polarity. We are also studying the function of a -TRCP/slimb related gene which we call
slm-1. -TRCP/slimb related proteins are known to function with GSK-3 to target proteins for proteolytic degradation. Interestingly,
slm-1 embryos have many phenotypic similarities with
sgg-1 embryos. We are performing more phenotypic analyses to better understand the functions of
sgg-1 and
slm-1 during C. elegans embryogenesis. 1 Schlesinger et al., Genes & Dev. (1999)