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

Citations Over TimeTop 11% of 2011 papers

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.

Related Papers

• → Slower cycling of nestin-positive cells in neurosphere culture(2006)11 cited
• → Kir4.1 is coexpressed with stemness markers in activated astrocytes in the injured brain and a Kir4.1 inhibitor BaCl₂ negatively regulates neurosphere formation in culture(2021)1 cited
• Culture and biological characteristics of brain tumor stem cells(2011)
• Nestin Immunohistochemical Staining on Paraffin Embedded Neurospheres(2005)
• → Direct induction versus neurosphere induction of neural cells from rat adipose stromal cells: a comparative study(2009)