title: Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1.
abstract: Extracellular stimuli regulate neuronal differentiation and subtype specification during brain development, although the intracellular signaling pathways that mediate these processes remain largely unclear. We now show that the PDK1-Akt pathway regulates differentiation of telencephalic neural precursor cells (NPCs). Active Akt promotes differentiation of NPC into gamma-aminobutyric acid-containing (GABAergic) but not glutamatergic neurons. Disruption of the Pdk1 gene or expression of dominant-negative forms of Akt suppresses insulin-like growth factor (IGF)-1 enhancement of NPC differentiation into neurons in vitro and production of neocortical GABAergic neurons in vivo. Furthermore, active Akt increased the protein levels and transactivation activity of Mash1, a proneural basic helix-loop-helix protein required for the generation of neocortical GABAergic neurons, and Mash1 was required for Akt-induced neuronal differentiation. These results have unveiled an unexpected role of the PDK1-Akt pathway: a key mediator of extracellular signals regulating the production of neocortical GABAergic neurons.
authors: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors: Koji
authors: K
authors: Oishi
authors: Kenji
authors: K
authors: Watatani
authors: Yasuhiro
authors: Y
authors: Itoh
authors: Hideyuki
authors: H
authors: Okano
authors: François
authors: F
authors: Guillemot
authors: Kazunori
authors: K
authors: Nakajima
authors: Yukiko
authors: Y
authors: Gotoh
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D019579:Neocortex / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D064413:3-Phosphoinositide-Dependent Protein Kinases; D051792:Basic Helix-Loop-Helix Proteins; D007334:Insulin-Like Growth Factor I; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005680:gamma-Aminobutyric Acid; C499317:Ascl1 protein, mouse; C578564:Pdpk1 protein, mouse