BDNF/ TrkB interaction regulates migration of SVZ precursor cells via PI3-K and MAP-K signalling pathways.
Neuroblasts born in the subventricular zone (SVZ) migrate along the rostral migratory stream, reaching the olfactory bulb (OB) where they differentiate into local interneurons. Several extracellular factors have been suggested to control specific steps of this process. The brain-derived neurotrophic factor (BDNF) has been demonstrated to promote morphological differentiation and survival of OB interneurons. Here we show that BDNF and its receptor TrkB are expressed in vivo throughout the migratory pathway, implying that BDNF might also mediate migratory signals. By using in vitro models we demonstrate that BDNF promotes migration of SVZ neuroblasts, acting both as inducer and attractant through TrkB activation. We show that BDNF induces cAMP response element-binding protein (CREB) activation in migrating neuroblasts via phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAP-K) signalling. Pharmacological blockade of these pathways on SVZ explants significantly reduces CREB activation and impairs neuronal migration. This study identifies a function of BDNF in the SVZ system, which involves multiple protein kinase pathways leading to neuroblast migration.
Chiaramello
S
S
Department of Animal and Human Biology, University of Turin, 10123 Turin, Italy.
Dalmasso
G
G
Bezin
L
L
Marcel
D
D
Jourdan
F
F
Peretto
P
P
Fasolo
A
A
De Marchis
S
S
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology* / Q000254:growth & development; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D020928:Mitogen-Activated Protein Kinases