Toll-Like Receptor 3 Is a Negative Regulator of Embryonic Neural Progenitor Cell Proliferation

Toll-like receptors (TLRs) play important roles in innate immunity. Several TLR family members have recently been shown to be expressed by neurons and glial cells in the adult brain, and may mediate responses of these cells to injury and infection. To address the possibility that TLRs play a functio...

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Bibliographic Details
Published in:The Journal of neuroscience 2008-12, Vol.28 (51), p.13978-13984
Main Authors: Lathia, Justin D, Okun, Eitan, Tang, Sung-Chun, Griffioen, Kathleen, Cheng, Aiwu, Mughal, Mohamed R, Laryea, Gloria, Selvaraj, Pradeep K, ffrench-Constant, Charles, Magnus, Tim, Arumugam, Thiruma V, Mattson, Mark P
Format: Article
Language:English
Subjects:
Animals
Brain - cytology
Brain - embryology
Brief Communications
Cell Proliferation - drug effects
Cells, Cultured
Gene Expression Regulation, Developmental
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurons - cytology
Neurons - metabolism
Poly I-C - pharmacology
Signal Transduction - drug effects
Signal Transduction - physiology
Spheroids, Cellular - cytology
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Toll-Like Receptor 3 - drug effects
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - physiology
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Summary:Toll-like receptors (TLRs) play important roles in innate immunity. Several TLR family members have recently been shown to be expressed by neurons and glial cells in the adult brain, and may mediate responses of these cells to injury and infection. To address the possibility that TLRs play a functional role in development of the nervous system, we analyzed the expression of TLRs during different stages of mouse brain development and assessed the role of TLRs in cell proliferation. TLR3 protein is present in brain cells in early embryonic stages of development, and in cultured neural stem/progenitor cells (NPC). NPC from TLR3-deficient embryos formed greater numbers of neurospheres compared with neurospheres from wild-type embryos. Numbers of proliferating cells, as assessed by phospho histone H3 and proliferating cell nuclear antigen labeling, were also increased in the developing cortex of TLR3-deficient mice compared with wild-type mice in vivo. Treatment of cultured embryonic cortical neurospheres with a TLR3 ligand (polyIC) significantly reduced proliferating (BrdU-labeled) cells and neurosphere formation in wild type but not TLR3(-/-)-derived NPCs. Our findings reveal a novel role for TLR3 in the negative regulation of NPC proliferation in the developing brain.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.2140-08.2008