Brain Development
91
model system, signaling machineries in-
volved in neural induction were examined,
and a new genetic cascade has been pro-
posed (Fig. 1b). According to the hypothe-
sis, a balance of Wnt (see Fig. 2b) and FGF
(±broblast growth factor) signaling path-
ways is the most critical aspect of neural in-
duction at earlier stages (Fig. 1b). The BMP
signaling that ±nally determines the neural
tissue is well-incorporated in this model,
yet it remains elusive to what degree
this hypothesis can explain the intricate
machineries required to establish neural
tissue among various vertebrate species.
2
Early Patterning of the Neural Tissue Along
the A–P and D–V Axes
Neural induction events determine the
de±nitive area of future neural tissue
within the single-layered ectoderm, termed
neuroectoderm
. The neuroectoderm con-
sists of tall epithelial cells and is recog-
nizable as a sheet or plate. All complex
structures of the brain emerge from this
single-layered cellular sheet termed the
neural plate
(Fig.3a).Importantly,theneu-
ral plate has been exposed to different
environments along the A–P and dor-
sal–ventral (D–V) axes in the embryo. This
allows the neural plate to further adopt
distinct features in the central nervous sys-
tem (CNS). I next outline early patterning
events in the neural plate along the A–P
and D–V axes.
2.1
D–V Patterning in the Neural Plate/Tube
The neural plate rolls up, detaches from
the nonneural ectoderm, and ±nally zips
along the dorsal midline of the embryo
to form a tubelike structure, called the
neural tube
(Fig. 3a). The D–V axis in the
Fig. 1
Gastrulation and neural induction in various vertebrate species. (a) Gastrulation and neural
induction in an amphibian embryo. During gastrulation, bottle cells are observed around the
blastpore, allowing the involution of cells (a dotted arrow). Amphibian neural induction events
appear to be very dependent upon BMP (bone morphogenetic protein) signaling inhibition, in which
BMP antagonists such as Chordin, Noggin, Cerberus, Follistatin, and so on secreted from the
organizer play crucial roles. Regarding BMP signaling machineries, see Fig. 2(a) as BMP is a member
of the TGF-
β
superfamily. (b) Gastrulation and neural induction in chicken embryo. During
gastrulation, mesodermal cells detach from the epiblast layer and emigrate anterior-laterally (dotted
arrows), forming the primitive streak. In the latest model, chicken neural tissue can be formed by FGF
and Wnt signals earlier than gastrulation: At the blastula stage, only lateral epiblast (green) expresses
Wnt3A/8C, demarcating medial epiblast as the prospective neural tissue (light pink region). The Wnt
receptor, Frizzled8, is ubiquitously expressed by all epiblasts at this stage (regarding the Wnt
signaling pathway, see Fig. 2(b)). a, anterior; N, neural tissue; n, future neural tissue, p, posterior.
(c) Gastrulation, neural induction, and early anterior–posterior axis formation during mouse
development. Blue arrows indicate the crucial movement of cells in the endodermal layer,
determining anterior characters of the neuroectoderm. Expression of the secreted molecule, Cripto, is
dynamically regulated at earlier stages, and this is thought to be critical to initiate A–P patterning
events, including the endodermal cell movement as well as primitive-streak formation (purple
region). During gastrulation, mesodermal cells detach from the epiblast layer (light green region) and
emigrate just like those in the chicken embryo (dotted arrows). a, anterior; AVE, anterior visceral
endoderm (dark blue region); E, embryonic day; EGO, early gastrula organizer (red region); ne,
neuroectoderm (pink region); p, posterior; VE, visceral endoderm (light blue region). The light gray
shading indicates Cripto expression, and the axial mesoderm is colored by orange. (See color
plate p. xxii).
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