title: 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.
abstract: 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.
authors.affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Yanfu
authors.initials: Y
authors.lastname: Shen
authors.forename: Noriko
authors.initials: N
authors.lastname: Inoue
authors.forename: Klaus
authors.initials: K
authors.lastname: Heese
mesh_terms: 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
chemical_list: 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
references.citation: FEBS Lett. 2009 Oct 6;583(19):3247-53
references.pmid: 19755123
references.citation: Mol Cell Neurosci. 2004 Nov;27(3):255-66
references.pmid: 15519241
references.citation: Curr Neurovasc Res. 2009 Feb;6(1):42-53
references.pmid: 19355925
references.citation: J Biol Chem. 2000 Sep 15;275(37):28793-801
references.pmid: 10858440
references.citation: J Neurosci Res. 2002 Sep 15;69(6):848-60
references.pmid: 12205678
references.citation: Mol Biol Cell. 2009 Jan;20(1):188-99
references.pmid: 18971377
references.citation: J Neurosci Res. 2002 Sep 15;69(6):745-9
references.pmid: 12205667
references.citation: Curr Opin Neurobiol. 2005 Feb;15(1):49-57
references.pmid: 15721744
references.citation: Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):528-32
references.pmid: 17439428
references.citation: Nat Rev Neurosci. 2003 Apr;4(4):299-309
references.pmid: 12671646
references.citation: Stem Cells. 2006 Nov;24(11):2437-47
references.pmid: 16888285
references.citation: J Neurosci. 2005 Feb 9;25(6):1407-11
references.pmid: 15703394
references.citation: Nat Neurosci. 2001 Oct;4(10):977-8
references.pmid: 11559852
references.citation: Nat Neurosci. 2005 Jun;8(6):709-15
references.pmid: 15917835
references.citation: Nat Neurosci. 2005 May;8(5):616-25
references.pmid: 15852015
references.citation: J Neurosci. 2003 Mar 1;23(5):1730-41
references.pmid: 12629177
references.citation: Cancer Cell. 2004 Oct;6(4):347-60
references.pmid: 15488758
references.citation: Development. 2003 Apr;130(7):1391-402
references.pmid: 12588854
references.citation: J Biol Chem. 2006 Mar 24;281(12):7890-8
references.pmid: 16434391
references.citation: J Neurochem. 1997 Sep;69(3):954-67
references.pmid: 9282917
references.citation: Sci STKE. 2006 Dec 05;2006(364):cm7
references.pmid: 17148788
references.citation: Eur J Biochem. 2000 May;267(9):2624-31
references.pmid: 10785383
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7638-43
references.pmid: 12794186
references.citation: FEBS Lett. 2007 May 1;581(9):1851-8
references.pmid: 17433308
references.citation: Eur J Neurosci. 1999 Apr;11(4):1421-30
references.pmid: 10103137
references.citation: J Biol Chem. 1993 Jul 15;268(20):15150-7
references.pmid: 8325889
references.citation: Exp Neurol. 1997 Apr;144(2):350-60
references.pmid: 9168835
references.citation: Annu Rev Biochem. 2003;72:609-42
references.pmid: 12676795
references.citation: EMBO J. 1993 Aug;12(8):3083-94
references.pmid: 8344249
references.citation: Biochem J. 1998 Sep 1;334 ( Pt 2):297-314
references.pmid: 9716487
references.citation: EMBO J. 1999 Aug 2;18(15):4261-9
references.pmid: 10428964
references.citation: Nature. 1987 Feb 12-18;325(6105):593-7
references.pmid: 3027580
references.citation: Cell Res. 2006 Nov;16(11):857-71
references.pmid: 17088897
references.citation: Mol Cell Biol. 2007 Jun;27(11):3982-94
references.pmid: 17371842
references.citation: Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8616-20
references.pmid: 1528870
references.citation: Curr Alzheimer Res. 2006 Apr;3(2):109-21
references.pmid: 16611011
references.citation: J Neurosci Res. 2005 Jul 15;81(2):163-71
references.pmid: 15948155
references.citation: Neuron. 2002 May 16;34(4):499-502
references.pmid: 12062033
references.citation: J Neurosci. 1997 Apr 15;17(8):2683-90
references.pmid: 9092589
references.citation: J Biol Chem. 2001 Aug 10;276(32):30018-23
references.pmid: 11408475
references.citation: Neuron. 1993 May;10(5):963-74
references.pmid: 8494647
references.citation: Biochem J. 2006 Sep 15;398(3):577-83
references.pmid: 16716147
references.citation: Trends Neurosci. 2002 Jun;25(6):284-6
references.pmid: 12086739
references.citation: Neuron. 1993 May;10(5):975-90
references.pmid: 8494648
references.citation: J Neurosci. 2006 Nov 15;26(46):12089-99
references.pmid: 17108182
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64
references.pmid: 16939974
references.citation: Annu Rev Neurosci. 2001;24:677-736
references.pmid: 11520916
references.citation: Eur J Neurosci. 2007 Feb;25(3):649-58
references.pmid: 17328769
references.citation: Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):533-45
references.pmid: 17439429
references.citation: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5361-5
references.pmid: 7777512
references.citation: Cell. 1991 Sep 6;66(5):967-79
references.pmid: 1653651
references.citation: J Neurosci Res. 2004 Dec 15;78(6):761-9
references.pmid: 15505793
references.citation: J Neuroimmunol. 2000 Jul 10;107(1):42-9
references.pmid: 10808049
references.citation: Cell Res. 2007 Jan;17(1):37-41
references.pmid: 17211446
references.citation: J Biol Chem. 1997 May 16;272(20):13019-25
references.pmid: 9148911