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.
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.
Shen
Yanfu
Y
Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
Inoue
Noriko
N
Heese
Klaus
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000378:metabolism; D013997:Time Factors
D009414:Nerve Growth Factors; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D019089:Stem Cell Factor; D051057:Proto-Oncogene Proteins c-akt; C073922:neurotrophin 4
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