Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway.
Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway.
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DOI：
10.1371/journal.pone.0026766
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lipkin WI
中科院分区：
文献类型：
--
作者：
Yaddanapudi K;De Miranda J;Hornig M;Lipkin WI
Toll-like receptor 3 (TLR3) signaling has been implicated in neural stem/precursor cell (NPC) proliferation. However, the molecular mechanisms involved, and their relationship to classical TLR-mediated innate immune pathways, remain unknown. Here, we report investigation of the mechanics of TLR3 signaling in neurospheres comprised of epidermal growth factor (EGF)-responsive NPC isolated from murine embryonic cerebral cortex of C57BL/6 (WT) or TLR3 deficient (TLR3−/−) mice. Our data indicate that the TLR3 ligand polyinosinic-polycytidylic acid (PIC) negatively regulates NPC proliferation by inhibiting Sonic Hedgehog (Shh) signaling, that PIC induces apoptosis in association with inhibition of Ras-ERK signaling and elevated expression of Fas, and that these effects are TLR3-dependent, suggesting convergent signaling between the Shh and TLR3 pathways.
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