| Wnt signaling regulates HMG domain-containing transcription factors to direct cell fate decisions during animal development. Throughout most of embryogenesis in C. elegans, the HMG domain repressor POP-1 distinguishes the fates of anterior daughter cells from their posterior, and Wnt signaling down-regulates POP-1 activity in one posterior daughter called E. Here, we show that the genes mom-4 and lit-1 also are required to down-regulate POP-1, not only in E but also in other posterior daughters. Consistent with action in a common pathway, mom-4 and lit-1 exhibit similar mutant phenotypes and encode mitogen activated protein kinase (MAPK) pathway components homologous to vertebrate TAK1 and NLK, respectively. Furthermore, MOM-4 and TAK1 bind related proteins that promote their kinase activities. We conclude that a MAPK-related pathway cooperates with Wnt signal transduction to down-regulate the activity of the HMG domain protein POP-1. The function of the mom-4/lit-1 pathway is evolutionarily conserved as the vertebrate TAK1 and NLK also cooperate with the Wnt pathway to down-regulate HMG domain proteins related to POP-1.; This dissertation includes both my previously published and my coauthored materials. |
