bar-1 was identified in a screen for mutants affecting vulval development. In
bar-1 mutants, the Vulval Precursor Cells (VPCs) show defects in cell fate specification and adopt Fused fates more often than in wild-type animals.
bar-1 was cloned and found to encode a C. elegans homolog of the -catenin/Armadillo family of proteins that have two functions: cell adhesion and Wnt signaling.
bar-1 is required to maintain levels of lin-39Hox in the VPCs and mab-5Hox in the Q neuroblasts to enable these cells to adopt correct cell fates, suggesting a role for
bar-1 in Wnt signaling.
pry-1, an Axin homolog and a negative regulator of Wnt signaling, functions upstream of
bar-1 in the above processes.
pry-1 mutants display phenotypes associated with overactivation of the Wnt pathway and hence would be a good tool to isolate suppressors that could potentially identify other genes functioning in Wnt signaling in these processes. We have identified six suppressors from screening 5000 haploid genomes. We are in the process of characterizing the phenotypes of these suppressors and will determine if any of them are
bar-1alleles. In addition to
bar-1(
ga80) isolated in our lab, there are seven more alleles of
bar-1 that were isolated from screens done in the Kenyon lab and have not been further characterized. Efforts are underway to determine the nature of mutations in these alleles that leads to differences in severity of phenotypes amongst them. We know from work in our lab and others that
bar-1 functions through a Wnt signaling pathway to enable the VPCs to adopt correct cell fates. However, we know very little about how
bar-1 is regulated in the vulva to begin with. We used a series of
bar-1 promoter deletions made as transcriptional GFP fusions to determine the spatio-temporal expression patterns in the vulva and other places. Using the above analysis, we found a 1.1 kb piece of the
bar-1 promoter that was sufficient to drive
bar-1expression in the VPCs and another 1.1 kb piece that is sufficient to drive expression in the ventral cord neurons. We are in the process of analyzing smaller deletions within these 1.1 kb regions to find minimal enhancer elements required for expression in the VPCs and ventral cord neurons in the hope of identifying transcription factors that bind to these sites and regulate
bar-1 activity in vivo.