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Cortical neurons
Injections of [3H]-thymidine
Days of gestation
FIGURE 3.18 Birthdating studies in monkey further demon-
strate the inside-out pattern of cerebral cortical histogenesis. In the
monkey, where the histogenesis of the cerebral cortex is more pro-
tracted than in the rat, the production of the cortical neurons takes
place over a 50-day time period. By labeling the pregnant female
with 3H-thymidine at progressively later gestational ages, it is pos-
sible to determine the period of embryonic development when each
specific cortical layer is generated.
25 m m
generated early in CNS development, and then the
progenitor cells for the various neurons and glia coex-
isted, side by side with the radial glia. However,
Noctor et al. (2002) used a retrovirus to label small
numbers of cortical progenitor cells in slice cultures of
the cerebral cortex of mice to directly visualize their
genesis and migration (Figure 3.19). They found, to
their surprise, that the radial glia themselves were the
neuronal progenitors! Figure 3.19 shows an example of
one of the clones they found. When the slice is viewed
on the first day, the labeled cell is a single radial glial
cell, with a process extending the entire width of the
cerebral cortex; however, as they continue to analyze
the clone on subsequent days, they find that the radial
glia undergoes several cell divisions, and the progeny
are not additional radial glia but migrating immature
neurons. These neurons migrate along the radial glia
that generated them. In addition to having the mor-
phology of neurons, these migrating neurons label for
neuron-specific markers, while the radial glial cell that
generated them expresses proteins typical of radial
glia. These results have been confirmed by cell culture
studies of radial glia, as well as more sophisticated
genetic studies of mice in vivo. Thus, our current view
of the neuronal progenitor and the radial glia is that
they are the same cell.
Most neurons are generated from cell division
within the ventricular zone and migrate radially, either
by crawling along the radial glia or by somal translo-
cation. In addition to this predominantly medial
FIGURE 3.19 Live imaging of GFP labeled radial glia shows that
radial glia are the same cells as the progenitors. Noctor et al. (2002)
used a retrovirus to label small numbers of cortical progenitor cells
in slice cultures of the cerebral cortex of mice. In this example, they
found that the radial glia (arrowhead) has undergone several cell
divisions, and the progeny are migrating immature neurons (arrow).
The neurons migrate along the radial glia that generated them.
(From Noctor et al., 2001)
migration of the newly generated neurons, however, it
has been consistently noted that some populations of
cortical neurons migrate tangential to the cortical
surface. Lineage tracing studies give some indication
as to the degree of this dispersion. The progeny of
a progenitor cell labeled with a retrovirus can be
widely dispersed within the cortex. In addition,
chimeric animals expressing reporter genes show that
a substantial fraction of the cortical neurons are not
associated with nearby radial clusters of similar geno-
type. Observation of labeled neurons in cortical slice
cultures has directly demonstrated this tangential
migration of a subpopulation of the cells migrating out
of the ventricular zone (O¢Rourke et al., 1995).
In addition to the intrinsically generated, tangen-
tially migrating neuronal population, at least some
tangentially migrating cells are not derived from the
cortical ventricular zone at all, but instead migrate all
the way from the ventricular zone in a subcortical fore-
brain region, the lateral ganglionic eminence. Most of
the neurons of the cerebral cortex are pyramidal
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