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Volume 17, Number 20,
Issue of October 15, 1997
pp. 7850-7859
Copyright ©1997 Society for Neuroscience
Transforming Growth Factor- Null and Senescent Mice Show
Decreased Neural Progenitor Cell Proliferation in the Forebrain
Subependyma
Received May 14, 1997; revised July 23, 1997; accepted August 5, 1997.
Vincent Tropepe,
Constance
G. Craig,
Cindi M. Morshead, and
Derek van der Kooy
Neurobiology Research Group, Department of Anatomy and Cell
Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
The adult mammalian forebrain subependyma contains neural stem
cells and their progeny, the constitutively proliferating progenitor cells. Using bromodeoxyuridine labeling to detect mitotically active
cells, we demonstrate that the endogenous expression of transforming
growth factor- (TGF) is necessary for the full proliferation of
progenitor cells localized to the dorsolateral corner of the
subependyma and the full production of the neuronal progenitors that
migrate to the olfactory bulbs. Proliferation of these progenitor cells
also is diminished with age (in 23- to 25-months-old compared with 2- to 4-months-old mice), likely because of a lengthening of the cell
cycle. Senescence or the absence of endogenous TGF does not
affect the numbers of neural stem cells isolated in
vitro in the presence of epidermal growth factor. These results
suggest that endogenous TGF and the effects of senescence may
regulate the proliferation of progenitor cells in the adult
subependyma, but that the number of neural stem cells is maintained
throughout life.
Key words:
subependyma;
olfactory bulb;
progenitor cell;
stem
cell;
proliferation;
transforming growth factor-;
senescence
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