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The Journal of Neuroscience, November 15, 2001, 21(22):8854-8862
Multipotent Stem Cells from the Mouse Basal Forebrain Contribute
GABAergic Neurons and Oligodendrocytes to the Cerebral Cortex during
Embryogenesis
Wenlei
He,
Christine
Ingraham,
Lisa
Rising,
Susan
Goderie, and
Sally
Temple
Center for Neuropharmacology and Neuroscience, Albany Medical
College, Albany, New York 12208
During CNS development, cell migrations play an important role,
adding to the cellular complexity of different regions. Earlier studies
have shown a robust migration of cells from basal forebrain into the
overlying dorsal forebrain during the embryonic period. These immigrant
cells include GABAergic neurons that populate the cerebral cortex and
hippocampus. In this study we have examined the fate of other basal
forebrain cells that migrate into the dorsal forebrain, identifying
basal cells using an antibody that recognizes both early
(dlx1/2) and late (dlx 5/6) members of
the dlx homeobox gene family. We found that a
subpopulation of cortical and hippocampal oligodendrocytes are also
ventral-derived. We traced the origin of these cells to basal
multipotent stem cells capable of generating both GABAergic neurons and
oligodendrocytes. A clonal analysis showed that basal forebrain stem
cells produce significantly more GABAergic neurons than dorsal
forebrain stem cells from the same embryonic age. Moreover, stem cell
clones from basal forebrain are significantly more likely to contain both GABAergic neurons and oligodendrocytes than those from dorsal. This indicates that forebrain stem cells are regionally specified. Whereas dlx expression was not detected within basal stem cells growing
in culture, these cells produced dlx-positive products that are capable
of migration. These data indicate that the developing cerebral cortex
incorporates both neuronal and glial products of basal forebrain and
suggest that these immigrant cells arise from a common progenitor, a
dlx-negative basal forebrain stem cell.
Key words:
CNS stem cells; oligodendrocytes; GABAergic neurons; telencephalon; cerebral cortex; basal forebrain; progenitor cells; cell
fate; cell migration
Copyright © 2001 Society for Neuroscience 0270-6474/01/21228854-09$05.00/0
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