The Wnt signaling pathway is highly conserved, playing an integral part in development and homeostasis of metazoan organisms. This pathway regulates cell polarity, migration and fate determination and its mis-activation has been implicated in assorted birth defects and diseases, including many cancers. In C. elegans, Wnt signaling is required for embryonic and larval development. Homologs have been identified for most of the core pathway components, but only a handful of target genes have been found. The Eisenmann lab is interested in Wnt pathway regulation of cell fate determination, and has shown that Wnt/beta-catenin signaling is involved in fate specification of certain epithelial cells. My research interest is to identify C. elegans Wnt pathway target genes.

Using microarray analysis I identified 178 genes that are differentially expressed upon over-expression of ΔNTBAR-1/β–catenin, a stable variant of the Wnt pathway transcriptional activator. Stringent qRT-PCR analysis of these candidate genes showed that 39 are bona fide ΔNTBAR-1-responsive. For thirteen of these genes expression is also dependent on the pathway co-activator POP-1/TCF, and therefore they are considered to be strong putative Wnt pathway targets. Additionally, five of the candidate genes show DAF-16 dependence, one encodes a negative regulator of the Wnt pathway, and four encode cuticular collagens which are major components of the C. elegans exoskeleton.

In characterizing the putative Wnt pathway target genes a subset were found to be co-expressed both temporally and spatially. Of particular interest were a set of seven expressed during the L4 larval stage of development in the hypodermal cells of the head, tail and mid-body. Included among this set were the collagen-encoding genes. Phenotypes resulting from RNAi-mediated reduction of gene function support the hypothesis that several of these genes may be involved in C. elegans cuticle formation.

Finally, in this study I have identified a novel set of BAR-1-responsive genes, among which are a set of strong Wnt pathway targets. Further I believe I have uncovered a role for Wnt signaling in the formation of the C. elegans cuticle, a novel finding in the worm.