106
Brain Development
shown that the mouse neural plate at the
2- to 3-somite stage already possesses dif-
ferent competencies for gene expression
between the anterior and posterior regions
adjoining the Six3/Irx3 gene expression
boundary. This could depend partly on the
fact that the underlying axial mesoderm is
subdivided into the prechordal plate and
notochord just beneath the future ZLI at
this stage. In mouse embryos, it had been
difFcult to conFrm if similar units exist
because the embryonic development pro-
ceeds
in utero
. I performed a cell labeling
experiment at the early neural plate stages
using the whole embryo culture system
that allows recapitulating the development
in vitro
. According to the results, there are
cell populations around the 3-somite stage
destined to be only forebrain cells, and the
posterior limit of such cells appears to fall
on the future ZLI. At the ZLI, in later de-
velopmental stages, signaling molecules
such as Shh are expressed, implicating
them in an organizing role in patterning
the prosomeres.
Immediately after the differential com-
petency between the region anterior to the
future ZLI and that posterior to the fu-
ture ZLI, the ±MB is set as the Pax6 gene
expression boundary, which can also be
deFned as a compartment boundary at
the mouse 5-somite stage (±ig. 6c). In the
chicken system, the ±MB is revealed to be
molecularly established by the 11-somite
stage as the result of the mutually repulsive
interactions between Pax6 and Pax2/En1
(±ig. 6b).
It is still unclear when and how the other
prosomere boundaries are established dur-
ing early development. In the later stages of
mouse development, however, the bound-
ary between the future cerebral cortex (ctx)
and lateral ganglionic eminence (lge) has
been shown to be a compartment bound-
ary by E10.5. This boundary is called
the
zona limitans intertelencephalica
and
thought to correspond to the p4/5 limit.
According to the fate-mapping analyses in
the mouse neural plate, the future lge was
indeed demonstrated to be located more
anteriorly to the future ctx.
±or over several decades, it has been a
big problem to determine which region is
the anterior most and how the floor/roof
plate as well as the alar/basal boundary
ends in the forebrain. This is simply
because forebrain development could only
be traced by morphological landmarks.
However, recent gene expression analyses
provide a variety of landmarks in the brain,
and such molecular markers strengthen
the prosomeric model. In the prosomeric
model, the roof, alar, and basal plates
concentrically cross the midline of the
anterior most
neural
plate, disposing
the eyes and telencephalon within the
alar plate (±ig. 6b). Recent fate-mapping
analyses in chicken and mouse well
support the model (±ig. 6c).
Then, what molecular mechanism are
involved in maintaining the prosomere
organization at later stages of forebrain
development? Several transcription factors
are again implicated as their expression
delineates later prosomeres and/or the
boundaries. ±or example,
Pax6, Gsh2
,and
Dlx
genes demarcate restricted brain re-
gions along the D–V axis of the mouse
E12.5 telencephalon, which almost cor-
responds to the A–P axis of the neural
plate. Interestingly, it has been demon-
strated that cells from distinct regions
in the telencephalon segregate from each
other in a Ca
2
+
dependent manner if the
cells are dissociated and mixed together.
A cell surface carbohydrate epitope, CD15
(Lewis(x)), is expressed within the cortex
and suggested to be the candidate molecule
that mediates Ca
2
+
dependent segrega-
tion
in vivo
. In addition, several cadherins
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