THE BETA-CATENIN HOMOLOG BAR-1 AND LET-60 RAS COORDINATELY REGULATE THE HOX GENE LIN-39 DURING CAENORHABDITIS-ELEGANS VULVAL DEVELOPMENT

In C. elegans, the epithelial Pn.p cells adopt either a vulval precurs or cell fate or fuse with the surrounding hypodermis (the F fate). Our results suggest that a Wnt signal transduced through a pathway involv ing the beta-catenin homolog BAR-1 controls whether P3.p through P8.p adopt the vulval precursor cell fate. In bar-1 mutants, P3.p through P 8.p can adopt F fates instead of vulval precursor cell fates. The Wnt/ bar-1 signaling pathway acts by regulating the expression of the Hox g ene lin-39, since bar-1 is required for LIN-39 expression and forced l in-39 expression rescues the bar-1 mutant phenotype. LIN-39 activity i s also regulated by the anchor cell signal/let-23 receptor tyrosine ki nase/let-60 Ras signaling pathway. Our genetic and molecular experimen ts show that the vulval precursor cells can integrate the input from t he BAR-1 and LET-60 Ras signaling pathways by coordinately regulating activity of the common target LIN-39 Hox.