title: Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation.
abstract: 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.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Eitan
authors.initials: E
authors.lastname: Okun
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Tang
authors.forename: Kathleen
authors.initials: K
authors.lastname: Griffioen
authors.forename: Aiwu
authors.initials: A
authors.lastname: Cheng
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mughal
authors.forename: Gloria
authors.initials: G
authors.lastname: Laryea
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Selvaraj
authors.forename: Charles
authors.initials: C
authors.lastname: ffrench-Constant
authors.forename: Tim
authors.initials: T
authors.lastname: Magnus
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000196:embryology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018874:Spheroids, Cellular / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D051196:Toll-Like Receptor 3; D011070:Poly I-C