 |
 Previous Article | Next Article 
The Journal of Neuroscience, October 1, 2001, 21(19):7642-7653
The Ciliary Neurotrophic Factor/Leukemia Inhibitory
Factor/gp130 Receptor Complex Operates in the Maintenance of
Mammalian Forebrain Neural Stem Cells
Takuya
Shimazaki,
Tetsuro
Shingo, and
Samuel
Weiss
Genes & Development Research Group, Department of Cell Biology and
Anatomy, University of Calgary Faculty of Medicine, Calgary, Alberta,
Canada T2N 4N1
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  (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.
Key words:
neural stem cells; ciliary neurotrophic factor; leukemia
inhibitory factor receptor-deficient mice; gp130; stem cell
maintenance; astrocyte differentiation
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197642-12$05.00/0
This article has been cited by other articles:
|
|
|
|
 
O. Islam, X. Gong, S. Rose-John, and K. Heese
Interleukin-6 and Neural Stem Cells: More Than Gliogenesis
Mol. Biol. Cell,
January 1, 2009;
20(1):
188 - 199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Zhu, R. Hata, F. Cao, F. Gu, Y. Hanakawa, K. Hashimoto, and M. Sakanaka
Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function
FASEB J,
November 1, 2008;
22(11):
3866 - 3877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. B. White and M. R. Ziman
Genome-wide discovery of Pax7 target genes during development
Physiol Genomics,
October 8, 2008;
33(1):
41 - 49.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hisahara, S. Chiba, H. Matsumoto, M. Tanno, H. Yagi, S. Shimohama, M. Sato, and Y. Horio
From the Cover: Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation
PNAS,
October 7, 2008;
105(40):
15599 - 15604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Yang, S. A. Arnold, A. Habas, M. Hetman, and T. Hagg
Ciliary Neurotrophic Factor Mediates Dopamine D2 Receptor-Induced CNS Neurogenesis in Adult Mice
J. Neurosci.,
February 27, 2008;
28(9):
2231 - 2241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yanagisawa and R. K Yu
The expression and functions of glycoconjugates in neural stem cells
Glycobiology,
July 1, 2007;
17(7):
57R - 74R.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-Y. Chang, W. Sun, W. Ochiai, K. Nakashima, S.-Y. Kim, C.-H. Park, J. S. Kang, J.-W. Shim, A-Y. Jo, C.-S. Kang, et al.
Bcl-XL/Bax Proteins Direct the Fate of Embryonic Cortical Precursor Cells
Mol. Cell. Biol.,
June 15, 2007;
27(12):
4293 - 4305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. M. Vaccarino, D. M. Fagel, Y. Ganat, M. E. Maragnoli, L. R. Ment, Y. Ohkubo, M. L. Schwartz, J. Silbereis, and K. M. Smith
Astroglial Cells in Development, Regeneration, and Repair
Neuroscientist,
April 1, 2007;
13(2):
173 - 185.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Kanatsu-Shinohara, K. Inoue, N. Ogonuki, H. Miki, S. Yoshida, S. Toyokuni, J. Lee, A. Ogura, and T. Shinohara
Leukemia Inhibitory Factor Enhances Formation of Germ Cell Colonies in Neonatal Mouse Testis Culture
Biol Reprod,
January 1, 2007;
76(1):
55 - 62.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bauer and P. H. Patterson
Leukemia Inhibitory Factor Promotes Neural Stem Cell Self-Renewal in the Adult Brain.
J. Neurosci.,
November 15, 2006;
26(46):
12089 - 12099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. M. Ganat, J. Silbereis, C. Cave, H. Ngu, G. M. Anderson, Y. Ohkubo, L. R. Ment, and F. M. Vaccarino
Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem Cells In Vivo.
J. Neurosci.,
August 15, 2006;
26(33):
8609 - 8621.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yoshimatsu, D. Kawaguchi, K. Oishi, K. Takeda, S. Akira, N. Masuyama, and Y. Gotoh
Non-cell-autonomous action of STAT3 in maintenance of neural precursor cells in the mouse neocortex
Development,
July 1, 2006;
133(13):
2553 - 2563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sakaguchi, T. Shingo, T. Shimazaki, H. J. Okano, M. Shiwa, S. Ishibashi, H. Oguro, M. Ninomiya, T. Kadoya, H. Horie, et al.
A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells
PNAS,
May 2, 2006;
103(18):
7112 - 7117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Bonaguidi, T. McGuire, M. Hu, L. Kan, J. Samanta, and J. A. Kessler
LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells
Development,
December 15, 2005;
132(24):
5503 - 5514.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Kokoeva, H. Yin, and J. S. Flier
Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy Balance
Science,
October 28, 2005;
310(5748):
679 - 683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Chen, Z. Mao, S. Liu, H. Liu, X. Wang, H. Wu, Y. Wu, T. Zhao, W. Fan, Y. Li, et al.
Dedifferentiation of Adult Human Myoblasts Induced by Ciliary Neurotrophic Factor In Vitro
Mol. Biol. Cell,
July 1, 2005;
16(7):
3140 - 3151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gregg and S. Weiss
CNTF/LIF/gp130 receptor complex signaling maintains a VZ precursor differentiation gradient in the developing ventral forebrain
Development,
February 1, 2005;
132(3):
565 - 578.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Chojnacki and S. Weiss
Isolation of a Novel Platelet-Derived Growth Factor-Responsive Precursor from the Embryonic Ventral Forebrain
J. Neurosci.,
December 1, 2004;
24(48):
10888 - 10899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Enwere, T. Shingo, C. Gregg, H. Fujikawa, S. Ohta, and S. Weiss
Aging Results in Reduced Epidermal Growth Factor Receptor Signaling, Diminished Olfactory Neurogenesis, and Deficits in Fine Olfactory Discrimination
J. Neurosci.,
September 22, 2004;
24(38):
8354 - 8365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ferron, H. Mira, S. Franco, M. Cano-Jaimez, E. Bellmunt, C. Ramirez, I. Farinas, and M. A. Blasco
Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells
Development,
August 15, 2004;
131(16):
4059 - 4070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Derouet, F. Rousseau, F. Alfonsi, J. Froger, J. Hermann, F. Barbier, D. Perret, C. Diveu, C. Guillet, L. Preisser, et al.
Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor
PNAS,
April 6, 2004;
101(14):
4827 - 4832.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gregg and S. Weiss
Generation of Functional Radial Glial Cells by Embryonic and Adult Forebrain Neural Stem Cells
J. Neurosci.,
December 17, 2003;
23(37):
11587 - 11601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. P. Ng, W. He, and N. Y. Ip
Leukemia Inhibitory Factor Receptor Signaling Negatively Modulates Nerve Growth Factor-induced Neurite Outgrowth in PC12 Cells and Sympathetic Neurons
J. Biol. Chem.,
October 3, 2003;
278(40):
38731 - 38739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Imitola, E. Y. Snyder, and S. J. Khoury
Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis
Physiol Genomics,
August 15, 2003;
14(3):
171 - 197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Martin, H.-D. Hofmann, and M. Kirsch
Glial Reactivity in Ciliary Neurotrophic Factor-Deficient Mice after Optic Nerve Lesion
J. Neurosci.,
July 2, 2003;
23(13):
5416 - 5424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Chojnacki, T. Shimazaki, C. Gregg, G. Weinmaster, and S. Weiss
Glycoprotein 130 Signaling Regulates Notch1 Expression and Activation in the Self-Renewal of Mammalian Forebrain Neural Stem Cells
J. Neurosci.,
March 1, 2003;
23(5):
1730 - 1741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bauer, S. Rasika, J. Han, C. Mauduit, M. Raccurt, G. Morel, F. Jourdan, M. Benahmed, E. Moyse, and P. H. Patterson
Leukemia Inhibitory Factor Is a Key Signal for Injury-Induced Neurogenesis in the Adult Mouse Olfactory Epithelium
J. Neurosci.,
March 1, 2003;
23(5):
1792 - 1803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Shingo, C. Gregg, E. Enwere, H. Fujikawa, R. Hassam, C. Geary, J. C. Cross, and S. Weiss
Pregnancy-Stimulated Neurogenesis in the Adult Female Forebrain Mediated by Prolactin
Science,
January 3, 2003;
299(5603):
117 - 120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-W. M. Koh
Ciliary Neurotrophic Factor Released by Corneal Endothelium Surviving Oxidative Stress Ex Vivo
Invest. Ophthalmol. Vis. Sci.,
September 1, 2002;
43(9):
2887 - 2896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Vallieres, I. L. Campbell, F. H. Gage, and P. E. Sawchenko
Reduced Hippocampal Neurogenesis in Adult Transgenic Mice with Chronic Astrocytic Production of Interleukin-6
J. Neurosci.,
January 15, 2002;
22(2):
486 - 492.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Shingo, S. T. Sorokan, T. Shimazaki, and S. Weiss
Erythropoietin Regulates the In Vitro and In Vivo Production of Neuronal Progenitors by Mammalian Forebrain Neural Stem Cells
J. Neurosci.,
December 15, 2001;
21(24):
9733 - 9743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
