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Although for many years it has been thought that
these different specializations occur later in develop-
ment, as a consequence of the specific connections with
other brain regions, more recent data indicates that the
different areas have distinct identities much earlier in
development, and these identities are not altered
by changes in innervation (see Grove and Fukuchi-
Shimogori, 2003). Like the other brain regions we have
been discussing, the cerebral cortex arises from a layer
of progenitors that comprises the early neural tube. In
the specific case of the cerebral cortex, the anterior-
most part of the neural tube, the telencephalon, is the
source of these progenitors (Figure 2.1). The regional
identities of the cortical areas can be monitored
through the analysis of transcription factor expression.
Two transcription factors that appear to have a role in
the specification of regional identities in cortex are pax6
( which we have already encountered for its role in
eye development) and emx2 . (Bishop et al., 2000;
Mallamaci et al., 2000; Muzio et al., 2002) These two
genes are expressed in opposing gradients across
the cortical surface (Figure 2.29). Emx2 is expressed
most highly in the caudo-medial pole, while pax6 is
expressed highest at the rostral-lateral pole. Mutations
in pax6 cause an expansion of emx2' s domain of expres-
sion and ultimately an expansion of the areas normally
derived from the caudal medial cortex, such as the
visual cortex. Mutations in emx2, by contrast, cause the
pax6 -expressing domain to expand, and ultimately
result in an expansion of the frontal and motor corti-
cal regions.
The graded patterns of expression of emx2 and pax6 ,
along with the many examples of signaling centers we
have already encountered in other regions of the
developing nervous system, have led many investiga-
Wnt
BMP
BMP
Neural plate
Shh
Notochord
Wnt
BMP
BMP
Shh
BMP
BMP
Wnt
Wnt
BMP
Somite
Shh
Shh
FIGURE 2.28 Shh is expressed first in the notochord and later in
the floorplate and induces ventral differentiation in the neural tube.
BMPs are expressed in the ectoderm overlying the neural tube and
then in the dorsal neural tube cells later in development. These two
signals antagonize one another, and through this mutual antagonism
they set up opposing gradients that control both the polarity of
spinal cord differentiation and the amount of spinal cord tissue that
differentiates into dorsal, ventral, and intermediate cell fates.
emx2 -/-
pax6 -/-
emx2
pax6
wt
M
M
M
M
S
S
M
M
S
S
A
A
A
A
S
V
V
S
V
V
V
V
A
A
FIGURE 2.29 Two transcription factors critical for the specification of regional identities in the cortex are
pax6 and emx2 . Emx2 is expressed primarily in the posterior cerebral cortex and then gradually diminishes
in expression toward the rostral cortical pole; pax6 has the complementary pattern of expression. Loss of
either the pax6 gene or the emx2 gene affects the cerebral cortical pattern of development. In the wild-type
(wt) animal, the motor cortex (M) is primarily located in the rostral cortex, and the other sensory areas for
somatosensation (S), auditory sensation (A), and visual perception (V) are located in the middle and poste-
rior cortex, respectively. In the emx2- deficient mice, the pattern is shifted caudally, and a greater area is occu-
pied by the motor cortex; by contrast, in the pax6- deficient mice, the visual cortex is expanded and the motor
cortex is severely reduced. (Modified from Muzio and Mallamaci, 2003)
 
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