title: PDK1 regulates the generation of oligodendrocyte precursor cells at an early stage of mouse telencephalic development.
abstract: During the development of the mouse telencephalon, multipotent neural precursor cells (NPCs) generate oligodendrocyte precursor cells (OPCs), progenitors restricted to the oligodendrocyte lineage, at various sites in a developmental stage-dependent manner. Although substantial progress has been made in identifying the transcription factors that control the production of OPCs, the signaling pathways that regulate these transcription factors and the spatiotemporal pattern of OPC production have been only partially clarified. Here, we show that the serine-threonine kinase 3-phosphoinositide-dependent kinase 1 (PDK1) contributes to an early wave of OPC production in the developing mouse telencephalon. Ablation of PDK1 in NPCs resulted in a reduction in the number of OPCs positive for Sox10 and platelet-derived growth factor receptor α (PDGFRα) within the neocortex and striatum at embryonic day (E) 15.5, but not at E18.5. Furthermore, pharmacological inhibition of phosphoinositide 3-kinase (PI3K) or deletion of the PDK1 gene suppressed the generation of OPCs from NPCs induced by fibroblast growth factor (FGF) 2 in culture. These results implicate the PI3K-PDK1 pathway in the physiological regulation of OPC production in a developmental context-dependent manner.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watatani
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D002454:Cell Differentiation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051379:Mice / Q000196:embryology*; D058953:Neural Stem Cells / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology*
chemical_list: D064413:3-Phosphoinositide-Dependent Protein Kinases; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; C578564:Pdpk1 protein, mouse