96
Brain Development
degree of Gli activation, it is assumed that
such differential concentrations of the Gli
molecule in cell nuclei affect the binding
possibility of the target genes, allowing the
distinct sets of downstream transcription
factors to be switched on/off.
In the dorsal half of the spinal cord,
distinct neuronal cell types are generated
at characteristic times and positions. The
identity and pattern of generation of these
dorsal neurons are shown to be dependent
initially on BMP-mediated signals that
derive from the epidermal ectoderm and
induce the dorsal midline cells called the
roof plate
. Roof plate cells are further
revealed to provide a secondary source of
TGF (transforming growth factor) beta-
related
signals
that
are
required
for
the
generation
of
distinct
classes
of
dorsal interneurons. Additionally, WNT-
secreted molecules are suggested to play
a crucial role in constituting the dorsal
cell types. For instance, when the
wnt
genes expressed at the dorsal midline
o
ft
h
en
e
u
r
a
lt
u
b
e(W
n
t
1a
n
dW
n
t
3
a
)
are
eliminated
by
gene
targeting
in
the mouse embryo, expansion of the
neural
crest
as
well
as
dorsal
CNS
progenitors is abolished. This indicates
that local WNT signaling is important
for the patterning and generation of
various types of cells in the dorsal neural
tube. Furthermore, neural crest induction
has been shown to involve interactions
between the neural plate (neuroectoderm)
and epidermal (surface) ectoderm: If an
isolated neuroectoderm and neural plate
are combined
in vitro
, neural crest cells
are induced at the interface between
these tissues. Recently, Wnt6 localized
in the early chicken surface ectoderm
has been demonstrated to play a role in
initiating neural crest induction, yet the
detailed molecular machinery including
the relationship between Wnt6 and BMP
signaling has not been determined.
The alar/basal boundary, which coin-
cides with the morphologically identi±able
sulcus limitans, has been proposed to
play a critical role in maintaining the
D–V pattern in the neural plate/tube
during development. Cadherin cell adhe-
sion molecules could be responsible for
the process, because one of the cadherin
subclasses, F-cadherin, is found to delin-
eate the alar/basal boundary cells, whereas
other subclasses of cadherins demarcate
a distinct cellular population in the frog
neural plate/tube. Cadherin is a trans-
membrane protein and is known to confer
rigid adhesiveness to cells in a Ca
2
+
de-
pendent manner (Fig. 5a). More than 20
subclasses have been cloned thus far, and
notable is the fact that each subclass has a
Fig. 5
Roles of cadherin cell adhesion molecules in embryogenesis (a) Cadherin is a
transmembrane protein that confers rigid adhesiveness to cells in a Ca
2
+
dependent manner. Several
molecules are known to interact with cadherin at the cytoplasmic domain, and they are important to
tether cadherins to the actin cytoskeltons. Cadherins might be involved in the Wnt signaling pathway,
as beta-catenin required for cadherin-mediated cell adhesion, is also a crucial element of Wnt
signaling (Fig. 2b). (b) Cells with a particular subclass of cadherin can only adhere to cells with the
same subclass of cadherin: when cells with different cadherin subclasses (red or blue) are mixed, they
sort out from each other in
in vitro
aggregation assays, although some pairs of cadherins show
heterotypic bindings. (c) During chicken neurulation, the expression pattern of cadherins is
dynamically regulated. Note that the changes of the cadherin expression patterns are tightly linked to
morphogenetic events, and it has been shown that overexpression of cadherins perturbs the
processes of neurulation as well as neural crest emigrations. (See color plate p. xxiv).
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