Differential MAP kinases activation during semaphorin3A-induced repulsion or apoptosis of neural progenitor cells.
Semaphorins are multifunctional factors implicated in various developmental processes. Little is known about the intracellular pathways ensuring appropriate signal transduction that encode the diverse functions observed. In this study, we investigated whether mitogen-activated protein kinases (MAPK), which are key elements of signal transduction in eukaryotic cells, were activated during semaphorin 3A (Sema3A)-induced repulsion or apoptosis of neural progenitor cells. We found that selective recruitment of the ERK1/2 pathway occurred during Sema3A-induced neural progenitor cell repulsion, whereas p38 MAPK activation was necessary for induction of apoptosis. Moreover, we provide evidence for the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) in the activation of ERK1/2. Additional experiments performed with native cerebellar progenitors confirmed such a selective recruitment of MAPK during Sema3A-dependent migration or apoptosis. Altogether, our results suggest a model to explain how a single factor can exert different functions for a given cell type by the selective recruitment of intracellular pathways.
Bagnard
D
D
INSERM U575, "Physiopathologie du Système Nerveux", 67084 Strasbourg, France. bagnard@neurochem-u-strasbg.fr
Sainturet
N
N
Meyronet
D
D
Perraut
M
M
Miehe
M
M
Roussel
G
G
Aunis
D
D
Belin
M F
MF
Thomasset
N
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D040121:Semaphorin-3A / Q000378:metabolism* / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D040121:Semaphorin-3A; D040281:Vascular Endothelial Growth Factor Receptor-1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases