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Neural crest
+ ectoderm
+ BMP 4/7
Neural crest
Neural crest
slug )
FIGURE 2.27 Liem et al. (1995) used an explant culture system to define the signals that specify dorsal
cell fates. The neural tube was dissected into a ventral piece, a dorsal piece, and an intermediate piece, and
the expression of genes normally restricted to either the dorsal neural tube or the ventral neural tube was
used to determine whether these genes were specifically induced by co-culture with the ectoderm. They found
that certain dorsally localized genes, like pax3 and msx1 , are initially expressed throughout the neural tube
and are progressively restricted from the ventral neural tube by Shh from the notochord and floorplate;
however, co-culture with the ectoderm was necessary to induce the expression of other, more definitive,
dorsal markers, like HNK1 and slug . BMPs were found to effectively replace the ectodermally derived signal,
since these could also activate HNK1 and slug, even from ventral explants.
since these could also activate HNK1 and slug , even
from ventral explants. Thus, there appears to be an
antagonism between Shh from the ventral neural tube
and BMPs from the dorsal neural tube; when BMP is
added along with Shh to the explants, the Shh -induced
motoneuron differentiation is suppressed.
In addition to the BMP signal that defines the border
of the neural tube, there is evidence that the wnt
signaling pathway plays a critical function in the spec-
ification of the neural crest fate (Deardorff et al., 2001).
Treatment of neural plate explants with wnt , like those
described for BMPs, is also sufficient to induce neural
crest markers in the cells (Garcia-Castro et al., 2002),
while blocking wnt signaling perturbs neural crest
development. Several wnt genes are expressed
in the developing ectoderm, adjacent to the point of
origin of the crest, including wnt8 and wnt6 . Using a
transgenic zebrafish line with a heat-inducible
inhibitor of wnt signaling, Lewis et al. (2004) were able
to precisely define the time in development when cells
require the signal to become crest. They found a criti-
cal period when inhibiting wnt signaling was able to
prevent neural crest development without affecting
development of neurons in the spinal cord.
The model of dorsal-ventral polarity in the spinal
cord that has emerged from these studies is as follows:
BMPs and wnt s, expressed at the margin of the neural
plate, induce the development of neural crest at the
boundary of the neural plate and the ectoderm (Figure
2.28). BMPs and wnt s are also important for the devel-
opment of the dorsal fates within the neural tube. Shh ,
expressed first in the notochord and later in the floor-
plate, induces ventral differentiation in the neural
tube. The Shh and BMP/ wnt signals antagonize one
another, and through this mutual antagonism they set
up opposing gradients that control both the polarity of
spinal cord differentiation and the amount of spinal
cord tissue that differentiates into dorsal, ventral, and
intermediate cell fates. Much more will be said about
the later stages of development of spinal cord cells in
Chapter 4.
The cerebral cortex, the largest region of the human
brain by far, is not a homogeneous structure, but rather
has many distinct regions, each of which has a dedi-
cated function. It has been known for over one
hundred years that there are significant variations in
the cellular structure (cytoarchitecture) of the cortex
from region to region. The different regions of the cere-
bral cortex were exhaustively classified into approxi-
mately 50 distinct areas by Brodmann (1909). Although
all neocortical areas have six layers, the relative
number of cells in each layer and the size of the cells
are quite variable and specialized to the specific func-
tion of that area. For example, the visual cortex, a
primary sensory area, has many cells in layer IV, the
input layer, whereas the motor cortex has very large
neurons in layer V, the output layer.
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