Sex myoblast migration in the Caenorhabditis elegans hermaphrodite represents a simple, genetically amenable model system for studying how cell migration is regulated during development. Two separable components of sex myoblast guidance have been described: a gonad-independent mechanism sufficient for the initial anterior migration to the mid-body region, and a gonad-dependent mechanism required for precise final positioning (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041-1052). Here, we demonstrate a role for a Ras-mediated signal transduction pathway in controlling sex myoblast migration. Loss-of-function mutations in
let-60 ras,
ksr-1,
lin-45 raf,
let-537/mek-2 or
sur-1/mpk-1 cause defects in sex myoblast final positions that resemble those seen in gonad-ablated animals, while constitutively active
let-60 ras(G13E) trans-genes allow fairly precise positioning to occur in the absence of the gonad. A mosaic analysis demonstrated that
let-60 ras is required within the sex myoblasts to control proper positioning. Our results suggest that gonadal signals normally stimulate
let-60 ras activity in the sex myoblasts, thereby making them competent to sense or respond to positional cues that determine the precise endpoint of migration.
let-60 ras may have additional roles in sex myoblast guidance as well. Finally, we have also investigated genetic interactions between
let-60 ras and other genes important for sex myoblast migration, including
egl-15, which encodes a fibroblast growth factor receptor tyrosine kinase (D. L. DeVore, H. R. Horvitz and M. J. Stern (1995) Cell 83, 611-623). Since mutations reducing Ras pathway activity cause a different phenotype than those reducing
egl-15 activity and since constitutive Ras activity only partially suppresses the migration defects of
egl-15 mutants, we argue that
let-60 ras and
egl-15 do not act together in a single linear pathway.