title: SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C. elegans.
abstract: Src family tyrosine kinase (SFK) has been implicated in the regulation of cell adhesion and migration during animal development. We show that SRC-1, an ortholog of SFK, plays an essential role in directing cell migration in Caenorhabditis elegans. The mutation in the src-1 gene results in defective distal tip cell (DTC)-directed gonad morphogenesis in an activity-dependent and DTC cell-autonomous manners. In the src-1 mutants, DTCs fail to turn and continue their centrifugal migration along the ventral muscles. The effect of the src-1 mutation is suppressed by mutations in genes that function in the CED/Rac pathway, suggesting that SRC-1 in DTCs is an upstream regulator of a Rac pathway that controls cytoskeletal remodeling. In the src-1 mutant, the expression of unc-5/netrin receptor is normally regulated, and neither the precocious expression of UNC-5 nor the mutation in the unc-5 gene significantly affects the DTC migration defect. These data suggest that SRC-1 acts in the netrin signaling in DTCs. The src-1 mutant also exhibits cell-autonomous defects in the migration and growth cone path-finding of Q neuroblast descendants AVM and PVM. However, these roles of SRC-1 do not appear to involve the CED/Rac pathway. These findings show that SRC-1 functions in responding to various extracellular guidance cues that direct the cell migration via disparate signaling pathways in different cell types.
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Bunsho
authors.initials: B
authors.lastname: Itoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirose
authors.forename: Nozomu
authors.initials: N
authors.lastname: Takata
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Nishiwaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Koga
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Ohshima
authors.forename: Masato
authors.initials: M
authors.lastname: Okada
mesh_terms: D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D006066:Gonads / Q000254:growth & development; D020439:Growth Cones / Q000502:physiology*; D051548:Histone Acetyltransferases; D009154:Mutation; D000075386:Netrin Receptors; D056920:Nuclear Receptor Coactivator 1; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D011505:Protein-Tyrosine Kinases