Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.
Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.
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DOI：
10.1523/jneurosci.2140-08.2008
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发表时间：
2008-12-17
期刊：
影响因子：
--
通讯作者：
Mattson MP
中科院分区：
文献类型：
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作者：
Lathia JD;Okun E;Tang SC;Griffioen K;Cheng A;Mughal MR;Laryea G;Selvaraj PK;ffrench-Constant C;Magnus T;Arumugam TV;Mattson MP
Toll样受体（TLR）在天然免疫中起重要作用。一些TLR家族成员最近已被证明在成人大脑中的神经元和神经胶质细胞中表达，并且可能介导这些细胞对损伤和感染的反应。为了解决TLR在神经系统发育中发挥功能性作用的可能性，我们分析了TLR在小鼠脑发育不同阶段的表达，并评估了TLR在细胞增殖中的作用。TLR 3蛋白存在于发育早期胚胎阶段的脑细胞和培养的神经干/祖细胞（NPC）中。与野生型胚胎的神经球相比，TLR 3缺陷胚胎的NPC形成了更多的神经球。增殖细胞的数量，磷酸化组蛋白H3（PH 3）和增殖细胞核抗原（PCNA）标记评估，也增加了TLR 3缺陷型小鼠在体内相比，野生型小鼠的皮质发育。用TLR 3配体（polyIC）处理培养的胚胎皮质神经球显著减少了WT中增殖（BrdU标记）细胞和神经球形成，但对TLR 3 −/−衍生的NPC没有影响。我们的研究结果揭示了TLR 3在发育中的脑中NPC增殖的负调控中的新作用。
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 to neurospheres from wild-type embryos. Numbers of proliferating cells, as assessed by phospho histone H3 (PH3) and proliferating cell nuclear antigen (PCNA) labeling, were also increased in the developing cortex of TLR3-deficient mice compared to 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 WT but not TLR3−/− derived NPCs. Our findings reveal a novel role for TLR3 in the negative regulation of NPC proliferation in the developing brain.