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Author Notes:

Wenhui Hu, M.D., Ph.D., 3500 N Broad Street, Philadelphia, Pennsylvania 19140, USA. Telephone: 215-707-5164; Fax: 215-707-4888; whu@temple.edu; or Xianming Mo, M.D., Ph.D., #1, Keyuan 4 Lu, High Tech District, Chengdu 610041, People’s Republic of China. Telephone: 86-2885164017; Fax: 86-2885164047; xmingmo@Yahoo.com.

Y.Z. and J.L.: performance of experiments and data analysis.

S.Y., F.L, W.Y., and S.K.: animal breeding and technical assistance; L.X., M.L., H.X., W.M., S.L., L.Y., J.L., and H.Z.: collection and assembly of data; V.B. and J.G.: data analysis and interpretation and manuscript editing; K.K., S.S., and J.R.B.: provision of materials and concept and design; X.M. and W.H.: conception and design, financial support, data analysis and interpretation, manuscript writing, performance of experiments, and final approval of manuscript.

Y.Z., J.L., X.M., and W.H. contributed equally to this article.

The authors indicate no potential conflicts of interest.

Subjects:

Research Funding:

This work was supported by the grants from the National Basic Research Program of China to X.M. (2007CB947802), the Nature Science Foundation of China to H.X. (30771228) and X.M. (30771227), and the National Institutes of Diabetes, and Kidney and Digestive Diseases to W.H. (DK075964) and S.S. (DK080684).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell & Tissue Engineering
  • Biotechnology & Applied Microbiology
  • Oncology
  • Cell Biology
  • Hematology
  • Neural stem cells
  • Nuclear factor kappa B
  • Neurogenesis
  • C/EBP beta
  • Glial fibrillary acidic protein
  • Cell division
  • ADULT HIPPOCAMPAL NEUROGENESIS
  • IN-VIVO
  • SUBVENTRICULAR ZONE
  • PROGENITOR CELLS
  • NEURONAL DIFFERENTIATION
  • ASYMMETRIC SEGREGATION
  • STEM/PROGENITOR CELLS
  • SYNAPTIC PLASTICITY
  • P50-DEFICIENT MICE
  • PROTEIN BETA

Nuclear Factor Kappa B Signaling Initiates Early Differentiation of Neural Stem Cells

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Journal Title:

STEM CELLS

Volume:

Volume 30, Number 3

Publisher:

, Pages 510-524

Type of Work:

Article | Post-print: After Peer Review

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.

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© AlphaMed Press.

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