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The Journal of Neuroscience, April 1, 2003, 23(7):2824
The Predominant Neural Stem Cell Isolated from Postnatal and
Adult Forebrain But Not Early Embryonic Forebrain Expresses GFAP
Tetsuya
Imura1,
Harley
I.
Kornblum2, 3, and
Michael V.
Sofroniew1
Departments of 1 Neurobiology,
2 Pharmacology, and 3 Pediatrics, and Brain
Research Institute, University of California, Los Angeles, California
90095-1763
Periventricular germinal zones (GZs) of developing and adult brain
contain neural stem cells (NSCs), the cellular identities and origins
of which are not defined completely. We used tissue culture techniques
and transgenic mice expressing herpes simplex virus thymidine kinase
(HSV-TK) from the mouse glial fibrillary acid protein (GFAP) promoter
to test the hypothesis that certain NSCs express GFAP. To do so, we
determined the relative proportions of multipotent neurospheres that
are formed by GFAP-expressing cells derived from GZs at different
stages of development. In this transgenic model, dividing
GFAP-expressing cells are ablated selectively by treatment with the
antiviral agent ganciclovir (GCV). Single-cell analysis showed that
transgene-derived HSV-TK was present only in GFAP-expressing cells. GCV
applied in vitro eliminated growth of multipotent
neurospheres from GZs of postnatal and adult transgenic mice but not
early embryonic (embryonic day 12.5) transgenic mice. GCV prevented
growth of secondary multipotent neurospheres prepared after passage of
primary transgenic neurospheres derived from all three of these
developmental stages. In addition, GCV prevented growth of multipotent
neurospheres from transgenic astrocyte-enriched cell cultures derived
from postnatal GZ, and elaidic acid GCV given for 4 d to adult
transgenic mice in vivo abolished the ability to grow
multipotent neurospheres from GZ. Extensive control experiments,
including clonal analysis, demonstrated that failure of neurosphere
growth was not merely secondary to loss of GFAP-expressing support
cells or the result of a nonspecific toxic effect. Our findings
demonstrate that the predominant multipotent NSCs isolated from
postnatal and adult but not early embryonic GZs express GFAP, and that
NSCs exhibit heterogeneous expression of intermediate filaments during
developmental maturation
Key words:
neural stem cell; neural progenitor; neurogenesis; astrocyte; ventricular zone; brain; glial fibrillary acid protein
Copyright © 2003 Society for Neuroscience 0270-6474/03/2372824-09$05.00/0
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