94
Brain Development
tube (Fig. 3a). During the morphogenetic
processes to form the neural tube, termed
neurulation
, a group of cells delaminates
from the neural ridge/dorsal midline
(
neural
crest
) of the neural tube and
migrates to generate the
neural crest cells
.
These cells differentiate into components
of the peripheral nervous system (PNS)
as well as other types of cells including
bones (Fig. 3b). The neural crest cells
can produce such a variety of cell types
that they have often been designated as
the fourth germ layer. The timing of
neural crest cell emigration varies among
species. For example, mammalian cranial
neural crest cells emigrate before the
neural tube is closed, while chicken neural
crest cells ±rst migrate just after the
neural tube closure. The neurulation step
also varies from species to species. For
instance, in ±sh embryo, neuroectoderm
(the neural keel) ±rst segregates out from
the ectoderm layer as a group of cells,
and later a cavity is generated in the
middle of the segregated tissue to form
the neural tube. Another unique process,
observed in the posterior part of mouse
and chicken embryos, is termed
secondary
neurulation
. In this process, neural tissues
are segregated from a mixture of cells in
the tail bud and this forms the remainder
of the neural structures in the spinal
cord. The dorsalmost cells in the neural
tube differentiate to constitute the
roof
plate
, while the ventralmost cells form
the
floor plate
with distinct features and
functions (Fig. 3a). The
sulcus limitans
is
an anatomically distinguishable boundary
between the dorsal and ventral neural tube,
and the dorsal half of the neural tube
subdivided by this landmark is termed
the
alar plate
, while the ventral half is
called the
basal plate
(Fig. 3a). In the
mature spinal cord, sensory inputs from
the peripherals (i.e. dorsal root ganglia)
innervate the interneurons in the alar
plate (Fig. 3a). Then, the outputs from
interneurons either innervate the brain or
directly rule the motor neurons in the basal
plate, generating the motor outputs to the
peripherals (i.e. muscles) (Fig. 3a). This
organization along the D–V axis in the
spinal cord is also represented in the rest
of the CNS.
D–V differences in the neural tube
are patterned by the surrounding tissues,
among which the notochord and epider-
mal ectoderm (i.e. surface ectoderm) seem
to play pivotal roles. For example, if the
notochord is eliminated at early develop-
mental stages, no ventral identities are
known to emerge (Fig. 3c). Furthermore, if
the notochord is grafted into the medial re-
gion of the early chicken spinal cord, it has
been demonstrated that components in
the basal plate, such as the floor plate and
motor neurons, are ectopically induced
(Fig. 3c). The floor plate has also been
shown to have inducing activity, and a com-
ponent of the signaling molecules is the
secreted molecule Sonic hedgehog (Shh).
Both the notochord and floor plate cells
express this molecule during early neural
development, and experimental data sup-
port a working hypothesis whereby several
typesofmotorneuronsaswellasinterneu-
rons are produced in response to the Shh
gradient along the D–V axis. According
to the hypothesis, the cells exposed to the
highest dose of Shh become the floor plate
cells, while those exposed to lower doses
constitute the distinct progenitor domains
in the ventricular zone. A gradient of Shh
signaling is also important to eventually
generate several types of motor neurons
and interneurons de±ned by a differen-
tial expression of transcription factors and
functions (Fig. 4a, b).
In vitro
experiments
have indeed con±rmed that different con-
centrations of Shh set strict thresholds to
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