Stem cell factor induces outgrowth of c-kit-positive neurites and supports the survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos.
The c-kit receptor tyrosine kinase is highly expressed by about 10% of the neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit-positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth. rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not express c-kit receptors on the cell surface and of W42/W42 mutant embryos that expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells. Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF-responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF did not support the survival of DRG neurons from embryos of W/W and W42/W42 genotypes. These results suggest that the stimulus through the c-kit receptor tyrosine kinase has an important role in development of the peripheral nervous system.
Hirata
T
T
Department of Pathology, Osaka University Medical School, Suita, Japan.
Morii
E
E
Morimoto
M
M
Kasugai
T
T
Tsujimura
T
T
Hirota
S
S
Kanakura
Y
Y
Nomura
S
S
Kitamura
Y
Y
D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor / Q000502:physiology*; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases