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

• Type of Material: Article
• Authors: Yonggang Zhang, Sichuan University; Jianjun Liu, Temple University; Shaohua Yao, Sichuan University; Fang Li, Temple University; Lin Xin, Sichuan University; Mowen Lai, Sichuan University; Valerie Bracchi-Ricard, University of Miami; Hong Xu, Sichuan University; William Yen, Temple University; Wentong Meng, Sichuan University; Shu Liu, Temple University; Leiting Yang, Temple University; Shaffiat Karmally, University of Miami; Jin Liu, Sichuan University; Hongyan Zhu, Sichuan University; Jennifer Gordon, Temple University; Kamel Khalili, Temple University; Shanthi Srinivasan, Emory University; John R. Bethea, University of Miami; Xianming Mo, Sichuan University; Wenhui Hu, Temple University
• Language: English
• Date: 2012-03-01
• Publisher: AlphaMed Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © AlphaMed Press.
• Final Published Version (URL): http://dx.doi.org/10.1002/stem.1006
• Title of Journal or Parent Work: STEM CELLS
• ISSN: 1066-5099
• Volume: 30
• Issue: 3
• Start Page: 510
• End Page: 524
• Grant/Funding Information: 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: Oncology; SUBVENTRICULAR ZONE; Life Sciences & Biomedicine; IN-VIVO; Cell Biology; Neurogenesis; P50-DEFICIENT MICE; Nuclear factor kappa B; PROTEIN BETA; Glial fibrillary acidic protein; C/EBP beta; Cell & Tissue Engineering; SYNAPTIC PLASTICITY; PROGENITOR CELLS; Cell division; ASYMMETRIC SEGREGATION; Hematology; ADULT HIPPOCAMPAL NEUROGENESIS; STEM/PROGENITOR CELLS; Biotechnology & Applied Microbiology; Science & Technology; Neural stem cells; NEURONAL DIFFERENTIATION
• Research Categories: Biology, Neuroscience; Biology, Microbiology; Biology, Cell

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.