Cellular and Molecular Neurobiology

, Volume 30, Issue 6, pp 909–916 | Cite as

Neurotrophin-4 (Ntf4) Mediates Neurogenesis in Mouse Embryonic Neural Stem Cells Through the Inhibition of the Signal Transducer and Activator of Transcription-3 (Stat3) and the Modulation of the Activity of Protein Kinase B

  • Yanfu Shen
  • Noriko Inoue
  • Klaus HeeseEmail author
Original Research


The effect of neurotrophin-4 (Ntf4) on mouse embryonic (day-14) neural stem cell (mE14-NSC) fate determination and the mechanisms involved were investigated. Using primary mE14-NSCs, immunocytochemistry and molecular-cell biological methods, such as Western-blotting, we characterized the effect of Ntf4 on mE14-NSC differentiation. Obtained in-vitro data revealed an interesting phenomenon of Ntf4 action resulting in enhanced mE14-NSC commitment to progenitor cells of the neuronal lineage. During this process, Ntf4 suppresses the interleukin 6 (Il6) family receptor and the Notch signalling pathways by modulating their specific receptor cleavages. The observed lineage commitment is controlled via an Ntf4-mediated modulation of protein kinase B (PKB/Akt) activity and characterized by a decreased Stat3 (signal transducer and activator of transcription-3) phosphorylation status. These findings suggest that the Ntf4-activated signalling cascade is responsible for initiating a concert among sheddases, kinases, and phosphatases to mediate neurogenesis.


Neural stem cells Neurotrophin Lif receptor Phosphatase Ptpn11 Shp2 TrkB 



This study was supported by an A*STAR grant (BMRC/04/1/22/19/360) to K.H.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Molecular and Cell Biology, School of Biological Sciences, College of ScienceNanyang Technological UniversitySingaporeSingapore
  2. 2.Medical Center for Translational ResearchOsaka University HospitalSuitaJapan

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