title: Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor.
abstract: The dynamic and coordinated interaction between cells and their microenvironment controls cell migration, proliferation, and apoptosis, mediated by different cell surface molecules. We have studied the response of a neuroectodermal progenitor cell line, Dev, to a guidance molecule, semaphorin 3A (Sema3A), described previously as a repellent-collapsing signal for axons, and we have shown that Sema3A acts as a repellent guidance cue for migrating progenitor cells and, on prolonged application, induces apoptosis. Both repulsion and induction of cell death are mediated by neuropilin-1, the ligand-binding component of the Sema3A receptor. The vascular endothelial growth factor, VEGF165, antagonizes Sema3A-induced apoptosis and promotes cell survival, migration, and proliferation. Surprisingly, repulsion by Sema3A also depends on expression of VEGFR1, a VEGF165 receptor, expressed in Dev cells. Moreover, we found that these repulsive effects of Sema3A require tyrosine kinase activity, which can be attributed to VEGFR1. These results indicate that the balance between guidance molecules and angiogenic factors can modulate the migration, apoptosis (or survival), and proliferation of neural progenitor cells through shared receptors.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U433, Neurobiologie Experimentale et Physiopathologie, Faculté de Médecine Laënnec, 69372 Lyon cedex 08, France.
authors.forename: D
authors.initials: D
authors.lastname: Bagnard
authors.forename: C
authors.initials: C
authors.lastname: Vaillant
authors.forename: S T
authors.initials: ST
authors.lastname: Khuth
authors.forename: N
authors.initials: N
authors.lastname: Dufay
authors.forename: M
authors.initials: M
authors.lastname: Lohrum
authors.forename: A W
authors.initials: AW
authors.lastname: Puschel
authors.forename: M F
authors.initials: MF
authors.lastname: Belin
authors.forename: J
authors.initials: J
authors.lastname: Bolz
authors.forename: N
authors.initials: N
authors.lastname: Thomasset
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001667:Binding, Competitive / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D008527:Medulloblastoma / Q000378:metabolism; D018715:Microscopy, Video; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039942:Neuropilin-1; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D040121:Semaphorin-3A; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D000906:Antibodies; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D040121:Semaphorin-3A; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1