The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells

Takuya Shimazaki, Tetsuro Shingo, Samuel Weiss

Research output: Contribution to journalArticle

242 Citations (Scopus)

Abstract

The cytokines that signal through the common receptor subunit gp130, including ciliary neurotrophic factor (CNTF), interleukin-6, leukemia inhibitory factor (LIF) and oncostatin M, have pleiotropic functions in CNS development. Given the restricted expression domain of the CNTF receptor α (CNTFR) in the developing forebrain germinal zone and adult forebrain periventricular area, we have examined the putative role of CNTFR/LIFR/gp130-mediated signaling in regulating forebrain neural stem cell fate in vivo and in vitro. Analysis of LIFR-deficient mice revealed that a decreased level of LIFR expression results in a reduction in the number of adult neural stem cells. In adult LIFR heterozygote (+/-) mice, the number of neural stem cells and their progeny in the forebrain sub-ependyma and TH-immunoreactive neurons in the olfactory bulb were significantly reduced. Intraventricular infusion of CNTF into the adult mouse forebrain, in the absence or presence of epidermal growth factor (EGF), enhanced self-renewal of neural stem cells in vivo. Analyses of EGF-responsive neural stem cells proliferating in vitro found that CNTF inhibits lineage restriction of neural stem cells to glial progenitors, which in turn results in enhanced expansion of stem cell number. These results suggest that CNTFR/LIFR/gp130-mediated signaling supports the maintenance of forebrain neural stem cells, likely by suppressing restriction to a glial progenitor cell fate.

Original languageEnglish
Pages (from-to)7642-7653
Number of pages12
JournalJournal of Neuroscience
Volume21
Issue number19
DOIs
Publication statusPublished - 2001 Oct 1

Keywords

  • Astrocyte differentiation
  • Ciliary neurotrophic factor
  • Leukemia inhibitory factor receptor-deficient mice
  • Neural stem cells
  • Stem cell maintenance
  • gp 130

ASJC Scopus subject areas

  • Neuroscience(all)

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