Investigating GEI-4, a DSH-2 interacting protein, in Wnt pathway regulation

Asymmetric cell division is one mechanism that generates cellular diversity in multicellular organisms. In C. elegans, a variation of the Wnt pathway, the Wnt/βcatenin asymmetry pathway, regulates asymmetric cell division. One key component of the Wnt pathway is the cytoplasmatic scaffolding protein Dishevelled. In C. elegans, loss of the Dishevelled homolog, dsh-2, disrupts many asymmetric divisions. Through a yeast two hybrid interactome, DSH-2 has been reported to interact GEI-4, a novel protein that has not been previously implicated in Wnt signaling. Here, we describe genetic interactions between dsh-2 and gei-4 indicating that their physical interaction is biologically relevant. RNAi knockdown of gei-4 shows partial synthetic lethality with the loss of dsh-2. In addition, genetic interactions are observed between gei-4 and dsh-2 in the asymmetric division of the somatic gonadal precursor cells, Z1 and Z4. Our results support a role for GEI-4 in Wnt pathway regulation.