Lymphotoxin β receptor-mediated NFκB signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells

Journal of Neuroinflammation
Xiao XiaoWenhui Hu

Abstract

Lymphotoxin (LT) is a lymphokine mainly expressed in lymphocytes. LTα binds one or two membrane-associated LTβ to form LTα2β1 or LTα1β2 heterotrimers. The predominant LTα1β2 binds to LTβ receptor (LTβR) primarily expressed in epithelial and stromal cells. Most studies on LTβR signaling have focused on the organization, development, and maintenance of lymphoid tissues. However, the roles of LTβR signaling in the nervous system, particularly in neurogenesis, remain unknown. Here, we investigated the role of LTβR-mediated NFκB signaling in regulating neural lineage differentiation. The C57BL/6J wild-type and GFAP-dnIκBα transgenic mice were used. Serum-free embryoid bodies were cultured from mouse embryonic stem cells and further induced into neural stem/progenitor cells (NSCs/NPCs). Primary neurospheres were cultured from embryonic and adult mouse brains followed by monolayer culture for amplification/passage. NFκB activation was determined by adenovirus-mediated NFκB-firefly-luciferase reporter assay and p65/RelB/p52 nuclear translocation assay. LTβR mRNA expression was evaluated by quantitative RT-PCR and LTβR protein expression was determined by immunohistochemistry and Western blot analysis. Multilabeled immunocytochemistry o...Continue Reading

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Citations

Dec 24, 2019·Frontiers in Cell and Developmental Biology·Yoo Jin JungNigel H Greig
May 31, 2019·Frontiers in Immunology·Erica C Dresselhaus, Mollie K Meffert
Aug 23, 2020·International Journal of Molecular Sciences·Shaista AfrozYoshizo Matsuka
Feb 27, 2021·Frontiers in Immunology·Nina GorléRoosmarijn E Vandenbroucke
Jul 3, 2021·Cells·Karli MockenhauptTomasz Kordula

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Methods Mentioned

BETA
transgenic
PCR
Protein Assay
electrophoresis
Infrared Imaging
nuclear translocation

Software Mentioned

Prism GraphPad
LI
COR

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