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First published online 26 October 2005
doi: 10.1242/dev.02103
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1 Department of Oncogene Research, Research Institute for Microbial Diseases,
Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
2 RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan
3 Department of Biology, Faculty of Sciences, Kyushu University Graduate School,
Hakozaki, Fukuoka 812-8581, Japan
Author for correspondence (e-mail:
okadam{at}biken.osaka-u.ac.jp)
Accepted 23 September 2005
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.
Key words: Src family tyrosine kinase, SRC-1, Cell migration, Axon guidance, C. elegans
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