Brain Development
may therefore be required to prevent the
intermingling of cells between the alar and
basal plates. Overexpression of F-cadherin
in the frog neural tube indeed resulted
in the abnormal intermixing of cells in
the neural tube. Chicken cadherin-7, most
homologous to frog F-cadherin, further
delineates the sulcus limitans, suggesting
a conserved role for cadherins in main-
taining this important boundary between
the alar and basal plates during evolution
(Fig. 5c).
Curiously, in the process of neurula-
tion, the expression of cadherin subclasses
is dynamically regulated. In chicken em-
bryos, for instance, the neuroectoderm
loses E-cadherin expression and begins to
express N-cadherin (Fig. 5c). Cells at the
neural ridge then lose N-cadherin expres-
sion and begin to express cadherin-6B,
while the emigrating neural crest cells
switch off cadherin-6B expression and
acquire cadherin-7 expression (Fig. 5c).
These serial switches of cadherin sub-
classes during development are crucial,
as ectopic expression of N-cadherin in the
frog embryo causes abnormal segregation
between the ectoderm and neural tube.
Overexpression of N-cadherin or cadherin-
revealed to result in the deterioration of
neural crest cell emigration, indicating
that the spatiotemporal expression pat-
tern of cadherin is important for normal
development. The repressive transcription
factor, Slug/Snail, is known to be involved
in epithelial–mesenchymal transition pro-
cesses by downregulating E-cadherin ex-
in vitro
might control emigrations of neural crest
in vivo
, as Slug/Snail expression de-
lineates the neural fold during neural crest
emigrations. Yet, cadherin genes are huge
200 kbp) with large introns, and the
transcriptional machineries required for
the spatiotemporary restricted expression
of cadherins has been poorly investigated.
A–P Patterning in the Neural Plate/Tube
It is known that tissues surrounding the
future neuroectoderm at the gastrulation
stage help establish A–P patterning in
neural tissue. As I already mentioned
earlier, Nieuwkoop proposed a two-step
model in which an early activating sig-
nal has a role in inducing neural tissue
with an anterior character (i.e. forebrain).
Subsequently, a second posteriorizing or
transforming signal converts some of the
posterior neural tissues into an even more
posterior character (i.e. hindbrain and
spinal cord). Supporting this model, dis-
tinct tissues have been shown to induce
different axial characters. For instance, in
mice, it has been demonstrated that the
combined action of the AVE and the node-
derived axial mesoderm (prechordal plate)
was important to represent anterior neu-
ral characters (Fig. 1c). Various signaling
molecules required to establish the ante-
rior character have indeed been identi±ed.
For example, secreted molecules such as
induce anterior characters as the gene tar-
geting mice have severe defects only in
the anterior structures. Another secreted
molecule, Cripto with a cysteine rich and
EGF-like motif has further been shown
to be a crucial morphogen organizing the
mouse A–P axis (refer to Fig. 1c and the
legend). Regarding the posteriorizing sig-
nals, retinoids, Wnt, and FGF signaling
have been implicated as the candidates.
For instance, explants from the frog ante-
rior neural plate were shown to acquire the
posterior identity when treated with FGF.
Additional mechanisms must be involved
in the posteriorization, as a simple block of
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