title: Nuclear factor kappa B signaling initiates early differentiation of neural stem cells.
abstract: Inflammatory mediators, many of which activate the signaling of nuclear factor kappa B (NFκB), have received increasing attention in the field of neurogenesis. NFκB signaling regulates neurite outgrowth and neural plasticity as well as the proliferation/apoptosis and terminal differentiation of neural stem cells (NSCs). Early neurogenesis from NSCs produces identical progeny through symmetric division and committed daughter cells through asymmetric division. Here, we show that NFκB signaling is required for NSC initial differentiation. The canonical IKKβ/IκBα/p65 pathway is activated during the initial stages of neural differentiation induced by treatment with TNFα or withdrawal of epidermal growth factor/basic fibroblast growth factor. NSC-specific inhibition of NFκB in transgenic mice causes an accumulation of Nestin(+) /Sox2(+) /glial fibrillary acidic protein(+) NSCs. Inhibition of NFκB signaling in vitro blocks differentiation and asymmetric division and maintains NSCs in an undifferentiated state. The induction of initial differentiation and asymmetry by NFκB signaling occurs through the inhibition of C/EBPβ expression. Our data reveal a novel function of NFκB signaling in early neurogenesis and provide insight into the molecular mechanisms underlying neurodevelopmental disorders and neurodegenerative diseases.
authors.affiliation: Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yao
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Xin
authors.forename: Mowen
authors.initials: M
authors.lastname: Lai
authors.forename: Valerie
authors.initials: V
authors.lastname: Bracchi-Ricard
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: William
authors.initials: W
authors.lastname: Yen
authors.forename: Wentong
authors.initials: W
authors.lastname: Meng
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Leiting
authors.initials: L
authors.lastname: Yang
authors.forename: Shaffiat
authors.initials: S
authors.lastname: Karmally
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Shanthi
authors.initials: S
authors.lastname: Srinivasan
authors.forename: John R
authors.initials: JR
authors.lastname: Bethea
authors.forename: Xianming
authors.initials: X
authors.lastname: Mo
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; D051550:I-kappa B Kinase