CFZ-2

We have utilized several genetic screens to identify additional mutations that affect cell migration. To date we have analyzed molecularly one new gene, represented by the mutation cw49, which was isolated in the first screen. cw49 was interesting to us because mutants are defective in multiple cell migrations, suggesting that the gene is directly involved in the process of cell migration. We cloned the cw49 gene and found that cw49 was a mutation in cfz-2, which encodes a C. elegans Frizzled homolog. Frizzled proteins are receptors for Wnts. The C. elegans genome contains four Frizzled genes. Mutations in three had been reported previously, but mutations in cfz-2 had not. Therefore, our mutation provided the first inroads into the function of cfz-2. We have shown that CFZ-2 is expressed in a small number of cells, mostly in the anterior region of the embryo. We currently are asking whether CFZ-2 functions as a guidance receptor within migrating cells or to specify the fates of cells that in turn provide a guidance cue. We have gone on to identify Wnt proteins that are likely to function with CFZ-2 and have investigated the contributions of different Frizzleds to cell migration. These experiments revealed extensive redundancy and interaction between Wnt signaling pathways, which we continue to investigate. This is of great interest because, by focusing on these processes in the relatively simple nematode, we can begin to decipher the complex interactions between different Wnt signaling pathways.