Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling.
During telencephalic development, cells from the medial ganglionic eminence (MGE) are thought to migrate to the neocortex to give rise to a majority of cortical GABAergic interneurons. By combining time-lapse video-microscopy, immunofluorescence and pharmacological perturbations in a new in vitro migration assay, we find that MGE-derived cells migrate through the entire extent of the cortex and into the CA fields of the hippocampus, but avoid the dentate gyrus. Migrating neurons initially travel within the marginal zone and intermediate zone, and can enter the cortical plate from either location. Tangential migration is strongly stimulated by BDNF and NT4 and attenuated by the Trk-family inhibitor, K252a, suggesting that migration is regulated by TrkB signaling. Furthermore, TrkB-null mice show a significant decrease in the number of calbindin-positive neurons migrating tangentially in the embryonic cortex. BDNF and NT4 cause rapid activation of PI3-kinase in MGE cells, and inhibition of PI3-kinase (but not of MAP kinase or PLCgamma) dramatically attenuates tangential migration. These observations suggest that TrkB signaling, via PI3-kinase activation, plays an important role in controlling interneuron migration in the developing cerebral cortex.
Polleux
Franck
F
INSERM U.371, 18 avenue Doyen Lépine, 69675 Bron, France.
Whitford
Kristin L
KL
Dijkhuizen
Paul A
PA
Vitalis
Tania
T
Ghosh
Anirvan
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D018920:Coculture Techniques / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017950:Ganglia, Sensory / Q000166:cytology / Q000196:embryology; D049452:Green Fluorescent Proteins; D026121:Indole Alkaloids; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009025:Morpholines / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051966:Phospholipase C gamma; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D002867:Chromones; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007527:Isoenzymes; D008164:Luminescent Proteins; D009025:Morpholines; D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C049985:staurosporine aglycone; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C073922:neurotrophin 4