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Published on: November 29, 2016
SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C.
Bunsho Itoh1, Takashi Hirose, Nozomu Takata
1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
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.
Insights
SRC-1, a Src family tyrosine kinase (SFK), is crucial for cell migration in Caenorhabditis elegans. Its mutation disrupts gonad development by affecting distal tip cell guidance, highlighting SRC-1
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Genetics
Background:
- Src family tyrosine kinases (SFKs) regulate cell adhesion and migration in animal development.
- Understanding the specific roles of SFKs in directed cell migration is essential for developmental processes.
Purpose of the Study:
- To investigate the function of SRC-1, a Caenorhabditis elegans ortholog of SFK, in cell migration.
- To elucidate the signaling pathways regulated by SRC-1 during gonad morphogenesis and neuroblast migration.
Main Methods:
- Genetic analysis of src-1 mutants in Caenorhabditis elegans.
- Observation of distal tip cell (DTC) migration and gonad morphogenesis.
- Analysis of interactions with CED/Rac pathway genes and netrin signaling components (UNC-5).
Main Results:
- src-1 mutations cause defective DTC-directed gonad morphogenesis, with DTCs failing to turn and migrating aberrantly.
- SRC-1 acts upstream of the CED/Rac pathway in DTCs to control cytoskeletal remodeling.
- SRC-1 also mediates cell-autonomous migration and growth cone path-finding of neuroblast descendants independently of the CED/Rac pathway.
Conclusions:
- SRC-1 is essential for directed cell migration in Caenorhabditis elegans, functioning in both DTC guidance and neuroblast migration.
- SRC-1 integrates extracellular guidance cues through distinct signaling pathways (CED/Rac and potentially others) in different cell types.
- These findings reveal SRC-1's critical role in coordinating cell movements during development.
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