Nuclear factor kappa B signaling initiates early differentiation of neural stem cells

Yonggang Zhang, Jianjun Liu, Shaohua Yao, Fang Li, Lin Xin, Mowen Lai, Valerie Bracchi-Ricard, Hong Xu, William Yen, Wentong Meng, Shu Liu, Leiting Yang, Shaffiat Karmally, Jin Liu, Hongyan Zhu, Jennifer Gordon, Kamel Khalili, Shanthi Srinivasan, John R. Bethea, Xianming MoWenhui Hu

Research output: Contribution to journalArticle

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)510-524
Number of pages15
JournalSTEM CELLS
Volume30
Issue number3
DOIs
StatePublished - Mar 1 2012

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Keywords

  • C/EBPβ
  • Cell division
  • Glial fibrillary acidic protein
  • Neural stem cells
  • Neurogenesis
  • Nuclear factor kappa B

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Zhang, Y., Liu, J., Yao, S., Li, F., Xin, L., Lai, M., Bracchi-Ricard, V., Xu, H., Yen, W., Meng, W., Liu, S., Yang, L., Karmally, S., Liu, J., Zhu, H., Gordon, J., Khalili, K., Srinivasan, S., Bethea, J. R., ... Hu, W. (2012). Nuclear factor kappa B signaling initiates early differentiation of neural stem cells. STEM CELLS, 30(3), 510-524. https://doi.org/10.1002/stem.1006