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Journal of Neuroscience, Vol 12, 249-256, Copyright © 1992 by Society for Neuroscience
Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain
CM Morshead and D van der Kooy
Department of Anatomy, University of Toronto, Ontario, Canada.
The early development of the mammalian forebrain involves the massive
proliferation of the ventricular zone cells lining the lateral ventricles.
A remnant of this highly proliferative region persists into adult life,
where it is known as the subependymal layer. We examined the proliferation
kinetics and fates of the mitotically active cells in the subependyma of
the adult mouse. The medial edge, the lateral edge, and the dorsolateral
corner of the subependymal layer of the rostral portion of the lateral
ventricle each contained mitotically active cells, but the dorsolateral
region had the highest percentage of bromodeoxyuridine (BrdU)-labeled cells
per unit area. Repeated injections of BrdU over 14 hr revealed a
proliferation curve for the dorsolateral population with a growth fraction
of 33%, indicating that 33% of the cells in this subependymal region make
up the proliferating population. The total cell cycle time in this
population was approximately 12.7 hr, with an S-phase of 4.2 hr. To examine
the fate of these proliferating cells, we injected low concentrations of a
replication-deficient, recombinant retrovirus directly into the lateral
ventricles of adult mice for uptake by mitotically active subependymal
cells. Regardless of the survival time postinjection (10 hr, 1 d, 2 d, or 8
d), the number of retrovirally labeled cells per clone remained the same (1
or 2 cells/clone). This suggests that one of the progeny from each cell
division dies. Moreover, the clones remained confined to the subependyma
and labeled cells were not seen in the surrounding brain tissue. Thus,
while 33% of the dorsolateral subependymal cells continue to proliferate in
adult life, the fate of the postmitotic progeny is death.
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