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Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway.

ABSTRACT: 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.

SUBMITTER: Yaddanapudi K

PROVIDER: S-EPMC3201973 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway.

Yaddanapudi Kavitha K De Miranda Joari J Hornig Mady M Lipkin W Ian WI

PloS one 20111025 10

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 th ...[more]

PMID: 22046349

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Correction: Proliferation of Murine Midbrain Neural Stem Cells Depends upon an Endogenous Sonic Hedgehog (Shh) Source.

Project description:[This corrects the article DOI: 10.1371/journal.pone.0065818.].

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