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PMID: 11567054 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 19 ·2001-10-01 ·Pages 7642-53

Shimazaki T, Shingo T, Weiss S

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 alpha (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 subependyma 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.

MeSH Terms
Animals Antigens, CD/metabolism Cell Count Cell Differentiation/drug effects Cell Lineage Cells, Cultured Ciliary Neurotrophic Factor/metabolism,pharmacology Cytokine Receptor gp130 Epidermal Growth Factor/pharmacology Heterozygote Injections, Intraventricular Leukemia Inhibitory Factor Receptor alpha Subunit Macromolecular Substances Membrane Glycoproteins/metabolism Mice Mice, Knockout Neuroglia/cytology,metabolism Neurons/cytology,metabolism Olfactory Bulb/cytology,metabolism Prosencephalon/cytology,metabolism Receptor, Ciliary Neurotrophic Factor/genetics,metabolism Receptors, Cytokine/deficiency,genetics Receptors, OSM-LIF Signal Transduction/physiology Stem Cells/cytology,drug effects,metabolism Tyrosine 3-Monooxygenase/biosynthesis
Chemicals
Antigens, CD Ciliary Neurotrophic Factor Il6st protein, mouse Leukemia Inhibitory Factor Receptor alpha Subunit Lifr protein, mouse Macromolecular Substances Membrane Glycoproteins Receptor, Ciliary Neurotrophic Factor Receptors, Cytokine Receptors, OSM-LIF Cytokine Receptor gp130 Epidermal Growth Factor Tyrosine 3-Monooxygenase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Shimazaki T
Genes & Development Research Group, Department of Cell Biology and Anatomy, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1.
Shingo T
Weiss S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-10-01
Pages
7642-53
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762896
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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