Cadherin based adherens junctions (AJ) are important in epithelial morphogenesis and maintenance of epithelial shape. The absence of cadherin junction components has been associated with many epithelial cancers. One component of the cadherin-catenin AJ is alpha-catenin. Alpha-catenin acts to anchor the complex to the actin cytoskeleton; in addition it is also able to bind other proteins that are known to interact with both the AJ and the actin cytoskeleton. As a result alpha-catenin most likely acts to recruit additional proteins necessary for adhesion to the AJ. Due to this central role within the cadherin-catenin complex alpha-catenin is a potential site of AJ regulation. A further understanding of the pathways regulating the stability of these junctions could provide further insight into the mechanisms by which cancer cells become invasive. The C. elegans alpha-catenin homologue, hmp-1, is essential for ventral epidermal enclosure and elongation of the embryo. Embryos lacking zygotic hmp-1 expression are unable to elongate, resulting in a humpback (Hmp) phenotype. We have previously isolated a mutation of hmp-1(fe4) which appears to perturb, but not completely abolish HMP-1 function in C. elegans.Some genes involved in cadherin junction formation and regulation have been previously identified in C. elegans and other model systems. For example, unc-34 is the only member of the Ena/VASP family in C. elegans. This family of proteins act to regulate actin remodeling and localise to newly formed cadherin junctions. Loss of unc-34 does not result in a significant epithelial phenotype in wild type worms, but in the presence of the fe4 mutation embryos either fail to ventrally enclose or arrest as Hmp embryos, thus indicating a role for unc-34 within cadherin-mediated adhesion. Evidence has also been presented that the small GTPases; Rho, Rac and Cdc42; along with their associated signaling molecules could also have a role in the regulation of cadherin-mediated adhesion. We are performing non-biased genetic screens to identify additional suppressors and enhancers of the fe4 mutant phenotype. Our screening strategy allows the identification of mutations that genetically interact with hmp-1, but do not affect epithelial development in a wild-type hmp-1 background. The results of these screens will be an increased understanding of the composition of the C. elegans AJ, as well as the regulatory role that alpha-catenin and its interacting partners play within cadherin-catenin adhesion complexes.