title: A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309-0347, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sundaram
authors.forename: J
authors.initials: J
authors.lastname: Yochem
authors.forename: M
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins; D002465:Cell Movement / Q000235:genetics*; D012734:Disorders of Sex Development; D017238:Genes, Helminth; D011905:Genes, ras; D006066:Gonads / Q000502:physiology; D015801:Helminth Proteins / Q000235:genetics* / Q000502:physiology; D009030:Mosaicism; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics* / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012733:Sex Differentiation; D015398:Signal Transduction / Q000235:genetics*; D019076:Transgenes; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C066646:let-60 protein, C elegans; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins