The extracellular matrix glycoprotein tenascin-R regulates neurogenesis during development and in the adult dentate gyrus of mice

Jin Chong Xu, Mei Fang Xiao, Igor Jakovcevski, Elena Sivukhina, Gunnar Hargus, Yi Fang Cui, Andrey Irintchev, Melitta Schachner, Christian Bernreuther

Research output: Contribution to journalArticle

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-/-x 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.

Original languageEnglish (US)
Pages (from-to)641-652
Number of pages12
JournalJournal of cell science
Volume127
Issue number3
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Keywords

  • Dentate gyrus
  • Extracellular matrix
  • Mouse
  • Neural stem cells
  • Neurogenesis
  • Tenascin-R

ASJC Scopus subject areas

  • Cell Biology

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