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Journal of Neuroscience, Vol 16, 2649-2658, Copyright © 1996 by Society for Neuroscience
In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain
CG Craig, V Tropepe, CM Morshead, BA Reynolds, S Weiss and D van der Kooy
Deparment of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.
The lateral ventricle subependyma in the adult mammalian forebrain contains
both neural stem and progenitor cells. This study describes the in situ
modulation of these subependymal neural precursor populations after
intraventricular administration of exogenous growth factors. In vivo
infusion of epidermal growth factor (EGF) into adult mouse forebrain for 6
consecutive days resulted in a dramatic increase in the proliferation and
total number of subependymal cells and induced their migration away from
the lateral ventricle walls into adjacent parenchyma. Immediately after EGF
infusion, immunohistochemical characterization of the EGF-expanded cell
population demonstrated that >95% of these cells were EGF receptor- and
nestin-positive, whereas only 0.9% and 0.2% labeled for astrocytic and
neuronal markers, respectively. Seven weeks after EGF withdrawal, 25% of
the cells induced to proliferate after 6d of EGF were still detectable; 28%
of these cells had differentiated into new astrocytes and 3% into new
neurons in the cortex, striatum, and septum. Newly generated
oligodendrocytes were also observed. These in vivo results (1) confirm the
existence of EGF-responsive subependymal neural precursor cells in the
adult mouse forebrain and (2) suggest that EGF acts directly as a
proliferation, survival, and migration factor for subependymal precursor
cells to expand these populations and promote the movement of these cells
into normal brain parenchyma. Thus, in situ modulation of endogenous
forebrain precursor cells represents a novel model for studying neural
development in the adult mammalian brain and may provide insights that will
achieve adult replacement of neurons and glia lost to disease or trauma.
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F. M. Vaccarino
Stem Cells and Neuronal Progenitors and Their Diversity in the CNS: Are Time and Place Important?
Neuroscientist,
October 1, 2000;
6(5):
338 - 352.
[Abstract]
[PDF]
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R. Raballo, J. Rhee, R. Lyn-Cook, J. F. Leckman, M. L. Schwartz, and F. M. Vaccarino
Basic Fibroblast Growth Factor (Fgf2) Is Necessary for Cell Proliferation and Neurogenesis in the Developing Cerebral Cortex
J. Neurosci.,
July 1, 2000;
20(13):
5012 - 5023.
[Abstract]
[Full Text]
[PDF]
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M.-C. Amoureux, B. A. Cunningham, G. M. Edelman, and K. L. Crossin
N-CAM Binding Inhibits the Proliferation of Hippocampal Progenitor Cells and Promotes Their Differentiation to a Neuronal Phenotype
J. Neurosci.,
May 15, 2000;
20(10):
3631 - 3640.
[Abstract]
[Full Text]
[PDF]
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M. A. I. Aberg, N. D. Aberg, H. Hedbacker, J. Oscarsson, and P. S. Eriksson
Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus
J. Neurosci.,
April 15, 2000;
20(8):
2896 - 2903.
[Abstract]
[Full Text]
[PDF]
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V. Tropepe, B. L. Coles, B. J. Chiasson, D. J. Horsford, A. J. Elia, R. R. McInnes, and D. van der Kooy
Retinal Stem Cells in the Adult Mammalian Eye
Science,
March 17, 2000;
287(5460):
2032 - 2036.
[Abstract]
[Full Text]
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F. H. Gage
Mammalian Neural Stem Cells
Science,
February 25, 2000;
287(5457):
1433 - 1438.
[Abstract]
[Full Text]
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A. Dobi, M. Palkovits, C. G. Palkovits, M. A. Ring, and D. v. Agoston
Septamer Element-Binding Proteins in Neuronal and Glial Differentiation
J. Neurosci.,
February 1, 2000;
20(3):
1073 - 1084.
[Abstract]
[Full Text]
[PDF]
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D. J. Martens, V. Tropepe, and D. van der Kooy
Separate Proliferation Kinetics of Fibroblast Growth Factor-Responsive and Epidermal Growth Factor-Responsive Neural Stem Cells within the Embryonic Forebrain Germinal Zone
J. Neurosci.,
February 1, 2000;
20(3):
1085 - 1095.
[Abstract]
[Full Text]
[PDF]
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G. C. Kopen, D. J. Prockop, and D. G. Phinney
Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains
PNAS,
September 14, 1999;
96(19):
10711 - 10716.
[Abstract]
[Full Text]
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J. P. Wagner, I. B. Black, and E. DiCicco-Bloom
Stimulation of Neonatal and Adult Brain Neurogenesis by Subcutaneous Injection of Basic Fibroblast Growth Factor
J. Neurosci.,
July 15, 1999;
19(14):
6006 - 6016.
[Abstract]
[Full Text]
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M. F. Mehler and J. A. Kessler
Progenitor Cell Biology: Implications for Neural Regeneration
Arch Neurol,
July 1, 1999;
56(7):
780 - 784.
[Abstract]
[Full Text]
[PDF]
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B. J. Chiasson, V. Tropepe, C. M. Morshead, and D. van der Kooy
Adult Mammalian Forebrain Ependymal and Subependymal Cells Demonstrate Proliferative Potential, but only Subependymal Cells Have Neural Stem Cell Characteristics
J. Neurosci.,
June 1, 1999;
19(11):
4462 - 4471.
[Abstract]
[Full Text]
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B. Kirschenbaum, F. Doetsch, C. Lois, and A. Alvarez-Buylla
Adult Subventricular Zone Neuronal Precursors Continue to Proliferate and Migrate in the Absence of the Olfactory Bulb
J. Neurosci.,
March 15, 1999;
19(6):
2171 - 2180.
[Abstract]
[Full Text]
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G. Zupanc
Neurogenesis, cell death and regeneration in the adult gymnotiform brain
J. Exp. Biol.,
January 5, 1999;
202(10):
1435 - 1446.
[Abstract]
[PDF]
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E. Y. Snyder
Review : Neural Stem-Like Cells: Developmental Lessons with Therapeutic Potential
Neuroscientist,
November 1, 1998;
4(6):
408 - 425.
[Abstract]
[PDF]
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S. A. Azizi, D. Stokes, B. J. Augelli, C. DiGirolamo, and D. J. Prockop
Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats---similarities to astrocyte grafts
PNAS,
March 31, 1998;
95(7):
3908 - 3913.
[Abstract]
[Full Text]
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Y. Arsenijevic and S. Weiss
Insulin-Like Growth Factor-I Is a Differentiation Factor for Postmitotic CNS Stem Cell-Derived Neuronal Precursors: Distinct Actions from Those of Brain-Derived Neurotrophic Factor
J. Neurosci.,
March 15, 1998;
18(6):
2118 - 2128.
[Abstract]
[Full Text]
[PDF]
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K Dumstrei, C Nassif, G Abboud, A Aryai, A Aryai, and V Hartenstein
EGFR signaling is required for the differentiation and maintenance of neural progenitors along the dorsal midline of the Drosophila embryonic head
Development,
January 9, 1998;
125(17):
3417 - 3426.
[Abstract]
[PDF]
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T. Jacques, J. Relvas, S Nishimura, R Pytela, G. Edwards, C. Streuli, and C ffrench-Constant
Neural precursor cell chain migration and division are regulated through different beta1 integrins
Development,
January 8, 1998;
125(16):
3167 - 3177.
[Abstract]
[PDF]
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C. Morshead, C. Craig, and D van der Kooy
In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain
Development,
January 6, 1998;
125(12):
2251 - 2261.
[Abstract]
[PDF]
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S.-i. Sakakibara and H. Okano
Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development
J. Neurosci.,
November 1, 1997;
17(21):
8300 - 8312.
[Abstract]
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V. Tropepe, C. G. Craig, C. M. Morshead, and D. van der Kooy
Transforming Growth Factor-alpha Null and Senescent Mice Show Decreased Neural Progenitor Cell Proliferation in the Forebrain Subependyma
J. Neurosci.,
October 15, 1997;
17(20):
7850 - 7859.
[Abstract]
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G. Kempermann, H. G. Kuhn, and F. H. Gage
Genetic influence on neurogenesis in the dentate gyrus of adult mice
PNAS,
September 16, 1997;
94(19):
10409 - 10414.
[Abstract]
[Full Text]
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H. G. Kuhn, J. Winkler, G. Kempermann, L. J. Thal, and F. H. Gage
Epidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain
J. Neurosci.,
August 1, 1997;
17(15):
5820 - 5829.
[Abstract]
[Full Text]
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F. Doetsch, J. M. Garcia-Verdugo, and A. Alvarez-Buylla
Cellular Composition and Three-Dimensional Organization of the Subventricular Germinal Zone in the Adult Mammalian Brain
J. Neurosci.,
July 1, 1997;
17(13):
5046 - 5061.
[Abstract]
[Full Text]
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R. McKay
Stem Cells in the Central Nervous System
Science,
April 4, 1997;
276(5309):
66 - 71.
[Abstract]
[Full Text]
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S. Weiss, C. Dunne, J. Hewson, C. Wohl, M. Wheatley, A. C. Peterson, and B. A. Reynolds
Multipotent CNS Stem Cells Are Present in the Adult Mammalian Spinal Cord and Ventricular Neuroaxis
J. Neurosci.,
December 1, 1996;
16(23):
7599 - 7609.
[Abstract]
[Full Text]
[PDF]
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