Involvement of the phosphatidylinositol 3-kinase/rac1 and cdc42 pathways in radial migration of cortical neurons.
During cortical development, newly generated neurons migrate radially toward their final positions. Although several candidate genes essential for this radial migration have been reported, the signaling pathways regulating it are largely unclear. Here we studied the role of phosphatidylinositol (PI) 3-kinase and its downstream signaling molecules in the radial migration of cortical neurons in vivo and in vitro. The expression of constitutively active and dominant-negative PI 3-kinases markedly inhibited radial migration. In the neocortical slice culture, a PI 3-kinase inhibitor suppressed the formation of GTP-bound Rac1 and Cdc42 and radial migration. Constitutively active and dominant-negative forms of Rac1 and Cdc42 but not Akt also significantly inhibited radial migration. In migrating neurons, wild-type Rac1 and Cdc42 showed different localizations; Rac1 localized to the plasma membrane and Cdc42 to the perinuclear region on the side of the leading processes. These results suggest that both the PI 3-kinase/Rac1 and Cdc42 pathways are involved in the radial migration of cortical neurons and that they have different roles.
Konno
Daijiro
D
Department of Neuroscience (D13), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoshimura
Saori
S
Hori
Kei
K
Maruoka
Hisato
H
Sobue
Kenji
K
D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002867:Chromones / Q000494:pharmacology; D018274:Electroporation; D004622:Embryo, Mammalian / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D005982:Glutathione Transferase; D019869:Phosphatidylinositol 3-Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein