title: 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.
authors: Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors: Kavitha
authors: K
authors: Yaddanapudi
authors: Joari
authors: J
authors: De Miranda
authors: Mady
authors: M
authors: Hornig
authors: W Ian
authors: WI
authors: Lipkin
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology*; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000172:deficiency / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D008024:Ligands; C465570:Shh protein, mouse; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D011070:Poly I-C