SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C. elegans

• Published in: Development (Cambridge) Vol. 132; no. 23; pp. 5161 - 5172
• Main Authors: Itoh, Bunsho, Hirose, Takashi, Takata, Nozomu, Nishiwaki, Kiyoji, Koga, Makoto, Ohshima, Yasumi, Okada, Masato
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01-12-2005
• Subjects: Animals; Body Patterning; Caenorhabditis elegans; Caenorhabditis elegans - growth & development; Caenorhabditis elegans Proteins - physiology; Cell Movement - physiology; Gonads - growth & development; Growth Cones - physiology; Histone Acetyltransferases; Mutation; Netrin Receptors; Nuclear Receptor Coactivator 1; Protein-Tyrosine Kinases - physiology; Receptors, Cell Surface - physiology; Signal Transduction; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.02103

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.