Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.
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Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation. / 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.
in: J NEUROSCI, Jahrgang 28, Nr. 51, 51, 2008, S. 13978-13984.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.
AU - Lathia, Justin D
AU - Okun, Eitan
AU - Tang, Sung-Chun
AU - Griffioen, Kathleen
AU - Cheng, Aiwu
AU - Mughal, Mohamed R
AU - Laryea, Gloria
AU - Selvaraj, Pradeep K
AU - Ffrench-Constant, Charles
AU - Magnus, Tim
AU - Arumugam, Thiruma V
AU - Mattson, Mark P
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 28
SP - 13978
EP - 13984
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 51
M1 - 51
ER -
