In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain

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Journal of Neuroscience, Vol 16, 2649-2658, Copyright © 1996 by Society for Neuroscience

ARTICLE

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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Development, January 6, 1998; 125(12): 2251 - 2261.
[Abstract] [PDF]

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] [Full Text] [PDF]

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] [Full Text] [PDF]

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] [PDF]

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] [PDF]

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] [PDF]

R. McKay
Stem Cells in the Central Nervous System
Science, April 4, 1997; 276(5309): 66 - 71.
[Abstract] [Full Text]

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]