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E8.5
E10.5
p5-6
p3-4
Te lencephalon
emx2
p3/4
p1
Eye
p2
p1-2
M
M
r1-2
p5/6
emx1
r1
r2
r3
r3-7
r4
r5
r6
r7
FIGURE 2.19 Prosomeric model of forebrain development; lon-
gitudinal and transverse patterns of gene expression that subdivide
the neural tube into a grid of regional identities. The expression of
some of these genes is shown for the mouse embryo at two differ-
ent stages of development. Two genes of the emx class are expressed
in the telencephalon, one in the anterior half of the cerebral hemi-
spheres (emx1) and the other in the posterior half of the hemispheres
(emx2). Analysis of the expression patterns of additional genes has
led to the conclusion that the prosencephalon can be subdivided into
six prosomeres. They are numbered from caudal to rostral, and so
prosomere 1 is adjacent to the mesencephalon, P2 and P3 subdivide
what is traditionally known as the diencephalon, and P4, P5 , and P6
subdivide the telencephalon.
FIGURE 2.20 Ectopic eyes are formed when the Drosophila pax6
gene— eyeless —is misexpressed in other imaginal discs. Halder et al.
(1995) misexpressed the eyeless gene in the leg disc in the develop-
ing fly and found that an ectopic eye was formed in the leg. This
remarkable experiment argues for the concept that master control
genes organize entire fields, or structures during embryogenesis,
possibly by activating tissue specific cascades of transcription
factors. (Courtesy of Walter Gehring)
domain factors have yielded remarkable evidence that
these molecules are critically involved in defining the
regional identity of the anterior brain. There are now
many examples of regionally expressed transcription
factors that have essential roles in brain development,
but only a few will be mentioned. However, one prin-
ciple that emerges is that several different classes of
transcription factors are likely to be important in spec-
ifying the positional identity of cells in any particular
region of the brain.
A key class of transcription factors that are critical
for specifying regional differences in the nervous
system are the pax genes. These genes have a home-
odomain region, and they also have a second con-
served domain known as the paired box (named for its
sequence homology with the Drosophila segmentation
gene, paired ). There are nine different pax genes, and all
but two, pax1 and pax9 , are expressed in the develop-
ing nervous system (Chalepakis et al., 1993). Several of
these genes are also disrupted in naturally occurring
mouse mutations and human congenital syndromes,
and the defects observed in these conditions generally
correspond to the areas of gene expression. pax2 , for
example, is expressed in the developing optic stalk and
the otic vesicle of the embryo, and mutations in pax2
in mice and humans cause optic nerve abnormalities,
known as colobomas.
Perhaps the most striking example of Pax gene reg-
ulation of regional differentiation in the nervous
system comes from the studies of Pax6 . This gene is
expressed early in the development of the eye, when
this region of the neural plate is committed to giving
rise to retinal tissue. Humans with a heterozygous dis-
ruption of this gene exhibit abnormalities in eye devel-
opment, causing a condition known as aniridia (a lack
of formation of the iris). In mice and humans with a
homozygous disruption of this gene, the eyes fail to
develop past the initial optic vesicle stage. A homolo-
gous gene has also been identified in Drosophila (as
well as many other organisms), and mutations in this
gene also disrupt eye formation in flies. And even
more surprising, when this gene is misexpressed at
inappropriate positions in the embryo, ectopic eyes are
induced (Halder et al., 1995 (Figure 2.20). The ability
of a single gene to direct the development of an entire
sensory organ like the eye is striking, and while in flies
the Pax genes act as if they are at the top of a hierar-
chy, and can be thought of as coordinating the signals
and genes necessary to organize a “field” of the
embryo's development, the situation in vertebrates is
considerably more complex. The Pax6 gene is one of
several transcription factors that are expressed in the
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