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Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.


ABSTRACT: 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.

SUBMITTER: Lathia JD 

PROVIDER: S-EPMC2637819 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.

Lathia Justin D JD   Okun Eitan E   Tang Sung-Chun SC   Griffioen Kathleen K   Cheng Aiwu A   Mughal Mohamed R MR   Laryea Gloria G   Selvaraj Pradeep K PK   ffrench-Constant Charles C   Magnus Tim T   Arumugam Thiruma V TV   Mattson Mark P MP  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20081201 51


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 i  ...[more]

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