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tors to postulate that similar signaling centers adjacent
to the cortex regulate the regional expression of these
transcription factors. We have already encountered the
two most well-studied cortical patterning signals, FGF
and retinoic acid. The most dramatic results have come
from the studies of fgf8. fgf8 , along with related FGFs,
fgf17 , and fgf18 , are all expressed at the anterior pole
of the developing telencephalon. To analyze the role of
the FGF s in specifying cortical areal identity, Grove
and her colleagues have misexpressed fgf8 in different
positions within the developing cortex (Grove and
Fukuchi-Shimogori, 2003). These studies have moni-
tored the identity of cortical regions both using the
expression of region-specific transcription factors, like
pax6 and emx2, as well as analyzing later-developed
properties of a region, like the barrel fields of the
somatosensory map. Increasing the amount of fgf8 in
the anterior pole causes a downregulation of emx2 and
a caudal shift in the cortical regions, with an expansion
of the rostral regions (Figure 2.30). Blocking the
endogenous fgf8 signal, by expressing a nonfunctional
FGF receptor to bind up all the available fgf8, causes
the opposite result, a rostral-wards shift in the cortical
regional identities. Most dramatically, placing a source
of fgf8 in the caudal cortex causes the formation of a
duplicated, mirror image of cortical regions.
The graded pattern of expression of emx2 and pax6 ,
in part regulated by fgf8 and other FGF s from the ante-
rior pole, appears to represent an early stage in the
process by which areas of the cerebral cortex become
specialized for different functions. As we saw for the
segmentation of the fly embryo at the beginning of the
chapter, patterning is often accomplished by an initial
gradient of expression that becomes further subdi-
A
E
FGFs
Wp1
BMPs
WNTs
Wp2
B
C
D
Control
+Fgf8 rostrally
+Fgf8 caudally
original somatosensory map
new somatosensory map
ectopic FGF8
FIGURE 2.30 Fgf8 patterns the cerebral cortex. A. fgf8 is expressed at the anterior pole of the developing
telencephalon, while BMPs and wnt genes are expressed in the posterior pole. Grove and her colleagues have
misexpressed fgf8 in different positions within the developing cortex. B. In the normal mouse, the barrel fields
of the somatosensory map (yellow) are located near the middle of the cerebral cortex while fgf8 (red) is
expressed anteriorly and BMP (blue) is expressed posteriorly. C. Increasing the amount of fgf8 ( red) in the
anterior pole causes a caudal shift in the cortical regions, including the somatosensory map. D. Placing a bead
of fgf8 in the caudal cortex causes the formation of a duplicated, mirror image of the somatosensory map.
E. Micrograph of duplicated somatosory maps after the addition of an ectopic fgf8 bead. Wp1 is the original
map and Wp2 is the new map. (Modified from Grove and Fukuchi-Shimogori, 2003)
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