Generation of an environmental niche for neural stem cell development by the extracellular matrix molecular tenascin C

Emmanuel Garcion, Aida Halilagic, Andreas Faissner, Charles Ffrench-Constant

Research output: Contribution to journalArticlepeer-review

255 Citations (Scopus)

Abstract

Stem cells in the embryonic mammalian CNS are initially responsive to fibroblast growth factor 2 (FGF2). They then undergo a developmental programme in which they acquire epidermal growth factor (EGF) responsiveness, switch from the production of neuronal to glial precursors and become localized in specialized germinal zones such as the subventricular zone (SVZ). Here we show that extracellular matrix molecules act as regulators of this programme. Tenascin C is highly expressed in the SVZ, and transgenic mice lacking tenascin C show delayed acquisition of the EGF receptor. This results from alterations in the response of the stem cells to the growth factors FGF2 and bone morphogenic protein 4 (BMP4), which normally promote and inhibit acquisition of the EGF receptor, respectively. Tenascin C-deficient mice also have altered numbers of CNS stem cells and these stem cells have an increased probability of generating neurones when grown in cell culture. We conclude that tenascin C contributes to the generation of a stem cell 'niche' within the SVZ, acting to orchestrate growth factor signalling so as to accelerate neural stem cell development.

Original languageEnglish
Pages (from-to)3423-3432
Number of pages10
JournalDevelopment
Volume131
Issue number14
DOIs
Publication statusPublished - 15 Jul 2004

Keywords

  • Central nervous system
  • Differentiation
  • Gliogenesis
  • Growth factor
  • Neurogenesis
  • Neurosphere
  • Proliferation
  • Stem cell
  • Tenascin C

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