Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1

Koji Oishia, Kenji Watatani, Yasuhiro Itoh, Hideyuki Okano, Francois Guillemot, Kazunori Nakajima, Yukiko Gotoh

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 γ-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.

Original languageEnglish
Pages (from-to)13064-13069
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number31
DOIs
Publication statusPublished - 2009 Aug 4

Keywords

  • GABAergic neuronal differentiation
  • Neural precursor cells
  • Telencephalon

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1'. Together they form a unique fingerprint.

  • Cite this