title: The extracellular matrix glycoprotein tenascin-R regulates neurogenesis during development and in the adult dentate gyrus of mice.
abstract: Abnormal generation of inhibitory neurons that synthesize γ-aminobutyric acid (GABAergic) is characteristic of neuropsychological disorders. We provide evidence that the extracellular matrix molecule tenascin-R (TNR) - which is predominantly expressed by a subpopulation of interneurons - plays a role in the generation of GABAergic and granule neurons in the murine dentate gyrus by regulating fate determination of neural stem or progenitor cells (NSCs). During development, absence of TNR in constitutively TNR-deficient (TNR(-/-)) mice results in increased numbers of dentate gyrus GABAergic neurons, decreased expression of its receptor β1 integrin, increased activation of p38 MAPK and increased expression of the GABAergic specification gene Ascl1. Postnatally, increased GABAergic input to adult hippocampal NSCs in TNR(-/-) mice is associated not only with increased numbers of GABAergic and, particularly, parvalbumin-immunoreactive neurons, as seen during development, but also with increased numbers of granule neurons, thus contributing to the increased differentiation of NSCs into granule cells. These findings indicate the importance of TNR in the regulation of hippocampal neurogenesis and suggest that TNR acts through distinct direct and indirect mechanisms during development and in the adult.
authors: Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors: Jin-Chong
authors: JC
authors: Xu
authors: Mei-Fang
authors: MF
authors: Xiao
authors: Igor
authors: I
authors: Jakovcevski
authors: Elena
authors: E
authors: Sivukhina
authors: Gunnar
authors: G
authors: Hargus
authors: Yi-Fang
authors: YF
authors: Cui
authors: Andrey
authors: A
authors: Irintchev
authors: Melitta
authors: M
authors: Schachner
authors: Christian
authors: C
authors: Bernreuther
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000254:growth & development*; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism
chemical_list: D019063:Tenascin; C074638:tenascin R
keywords: Dentate gyrus; Extracellular matrix; Mouse; Neural stem cells; Neurogenesis; Tenascin-R