112
Brain Development
hindbrain,
Hox-a
and
Hox-b
genes have
been shown to regulate the identity as
well as the axonal projection pattern of
cranial motor neurons. Recently, a possible
role has been suggested for the secreted
molecules FGFs, Gdf11, and Retinoids in
regulating the
Hox-c
expression in the
motor neurons along the A–P axis. It
would be an intriguing subject in the
near future to see how the signals that
regulate A–P differences can interact with
those that de±ne the D–V axis (Shh)
and/or neuron/glia ratio (Notch/Delta) to
generate distinct types of neurons in a
timely and spatially restricted manner.
4.2
Nuclei Formation
To arrange cells into groups after cell
divisions, coordinated processes must be
required. First of all, the timing of cell
division has a role in sorting the ±nal
localization of neurons. For example, in
the spinal cord, motor neurons generated
at earlier stages are shown to occupy
the distal domain. Recently, Jessell and
colleagues have reported that cadherin
cell adhesion molecules demarcate distinct
populations of neurons in the chicken
spinal motor column. Using the
in vivo
EP technique (see Sect. 7), they showed
that neurons with the ectopic cadherin
subclass could localize in the subdivisions
of the motor column (pools) expressing
the
ectopic
cadherin,
implicating
the
cadherins in the important role of sorting
different subclass of neurons into a pool
within the spinal motor column during
development.
In the thalamus, there are many dis-
tinct subdivisions in the neurons, which
innervate speci±c telencephalic region. For
example, neurons in the medial geniculate
nucleus send axons to just the auditory
cortex, while those in the lateral geniculate
nucleus innervate only the visual cortex. As
is the case with the spinal motor neurons,
neurons produced at earlier stages usually
settle in the lateral subdivisions within a
thalamic nucleus. Recently, various types
of molecular markers such as transcription
factors (LIM homeodomain transcription
factors, Gbx2, Dlx1, Nkx2.2, Pax6, and so
on) and cell adhesion molecule cadherins
were found to demarcate speci±c subdivi-
sions. As cadherins have subclass speci±c
cell adhesiveness, differential expression
of cadherins may contribute to the segre-
gation of speci±c cells into the thalamus
subdivisions, just like the case with the
motor column segregations in the spinal
cord. Curiously, it has been reported that
secreted molecules such as the Shh ex-
pressed at the ZLI might regulate the
differential expression of transcription fac-
tors in the thalamus, implicating a genetic
cascade in the regulation of nucleus for-
mation, yet the detailed machineries have
been poorly studied.
4.3
Layer Formation
In the mammalian cerebral neocortex
there are six major layers (layers I to
VI), which can be distinguished by dif-
ferences in the morphology and density of
the neurons, with the thickness of each
layer varying from area to area. Neurons in
each cortical layer are generated in the ven-
tricular zone of the dorsal telencephalon
and travel toward the cortical plate located
in a remote position from their birthplace
using the radial glial ±bers as the migrat-
ing substrates, while some interneurons
are known to be generated in the ven-
tricular zone of the ventral telencephalon
and migrate tangentially. Cortical layers
are formed in an orderly manner from the
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