Distal tip cell (DTC) migration is a genetically tractable, simple model system for studying the developmental control of cell migration. In order to further elucidate the mechanism of DTC migration, we conducted a genome-wide RNA interference screen and evaluated the migration of the DTCs using light microscopy. In addition to proteins of known function, our genome-wide DTC migration screen identified many novel genes. One of these novel cell migration genes, W03H9.4, is the homolog of Drosophila cactin, a regulator of NFKB, and is conserved throughout metazoa. W03H9.4 feeding RNAi commonly results in wandering, loopy DTC migration paths. Depletion of W03H9.4 also disrupts vulval formation, male ray formation, and fertility. Injection RNAi results in early embryonic lethality, indicating W03H9.4 is an essential gene. W03H9.4 is predicted to physically interact with key regulatory factors such as
icd-1, an inhibitor of cell death, and
eps-8, an actin capping protein and growth factor receptor kinase substrate. We are currently investigating these interactions using the yeast two hybrid system. Understanding how W03H9.4 and other novel factors control DTC migration will provide important new insights into the mechanisms of cell migration.