Cm. Morshead et al., IN-VIVO CLONAL ANALYSES REVEAL THE PROPERTIES OF ENDOGENOUS NEURAL STEM-CELL PROLIFERATION IN THE ADULT MAMMALIAN FOREBRAIN, Development, 125(12), 1998, pp. 2251-2261
The adult mammalian forebrain contains a population of multipotential
neural stem cells in the subependyma of the lateral ventricles whose p
rogeny are the constitutively proliferating cells, which divide active
ly throughout life. The adult mammalian brain is ideal for examining t
he kinetics of the stem cells due to their strict spatial localization
and the limited and discrete type of progeny generated (constitutivel
y proliferating cells). Clonal lineage analyses 6 days after retroviru
s infection revealed that under baseline conditions 60% of the constit
utively proliferating cells undergo cell death, 25% migrate to the olf
actory bulb and 15% remain confined to the lateral ventricle subependy
ma (where they reside for approximately 15 days). Analysis of single c
ell clones 31 days after retroviral infection revealed that the stem c
ell divides asymmetrically to self-renew and give rise to constitutive
ly proliferating cells. Following repopulation of the depleted subepen
dyma the average clone size is 2.8 times larger than control, yet the
absolute number of cells migrating to the olfactory bulb is maintained
and the stem cell retains its asymmetric mode of division. The number
of neural stem cells in the adult forebrain 33 days after repopulatio
n of the subependyma was estimated using bromodeoxyuridine labeling of
subepenydmal cells. There were calculated to be 1200-1300 cells betwe
en the rostral corpus callosum and rostral anterior commissure; these
data support a lineage model similar to those based on stem cell behav
ior in other tissue types.