Brain Development
99
FGF was not enough to abolish the poste-
rior patterning. Interactions among those
secreted molecules could generate the re-
gional differences of signaling events in
the downstream, eventually turning on
differential sets of transcription factors
to represent the morphological and func-
tional variations along the A–P axis in the
neural plate/tube.
Following the neural induction and/or
neurulation events, several bulges and
sulci become apparent in an orderly
manner in the anterior part of the neu-
ral plate/tube, generating the anatomi-
cally distinguishable segmented structures
along the A–P axis. This step is termed
seg-
mentation
and Fig. 6(a) shows how the ver-
tebrate anterior neural plate/tube can be
subdivided into major brain regions such
as the
forebrain, midbrain
,and
hindbrain
,
all of which have separable characteristics
compared with the posterior CNS region,
namely, the
spinal cord
. Within these ma-
jor brain regions, further bulges and
sulci
are generated, and these minimal brain
units, anatomically distinguishable during
development, are de±ned as
neuromeres
(Fig. 6c, 7c). Curiously, some of the neu-
romeres, which constitute the cell lineage
restricted compartment units, are consid-
ered to play a major role in maintaining
embryonic brain organization, because the
boundaries prevent cells, once patterned,
from random intermingling during devel-
opment. Neuromeres may further provide
a basic framework for complex neuronal
circuits since the neuromere boundaries
often coincide with the territories be-
tween functional brain subdivisions and
with initial axonal tracts in the embry-
onic brain. Next, I summarize genetic
mechanisms involved in A–P pattern-
ing within the (1) hindbrain (rhomben-
cephalon), (2) midbrain (mesencephalon),
and (3) forebrain (prosencephalon).
2.2.1
Hindbrain Specifcation
The hindbrain region later generates the
pons, cerebellum, and medulla. While
the cerebellum is thought to play a cen-
tral role in the coordination of complex
movements, the medulla is considered as
the critical center for involuntary activi-
ties such as respiration. The pons is also
an important turning point for various
nerve tracts. In the developing vertebrate
hindbrain, seven to eight segmental units
are morphologically recognizable. These
units are called
rhombomeres
and play a
crucial role in hindbrain patterning. For
instance, distinct types of cranial motor
neurons are differentiated at later stages
along rhombomere organization (Fig. 7c).
The neural crest migration pattern is also
determined by this segmental organiza-
tion, eventually affecting the metameric
craniofacial structures represented in the
branchial arches (Fig. 7c). What molecu-
lar mechanisms then regulate hindbrain
segmentation?
The Hox transcription factors are one
of the gene families that play a cen-
tral role in hindbrain segmentation.
Hox
genes are originally identi±ed as homologs
of the genes involved in the segmen-
tation of
Drosophila
embryos: The A–P
axis of
Drosophila
embryos is ±rst realized
as opposing maternal mRNA gradients
along the A–P axis of the egg, which
are translated into transcription factors
immediately after fertilization (Fig. 7a).
In response to the combinatorial con-
centration of these transcription factors,
differential sets of genes termed gap genes
are then turned on along the A–P axis
(Fig. 7a). Downstream of these gap gene
transcription factors, pair-rule genes are
activated (Fig. 7a), and ±nally, the seg-
ment polarity genes and the homeotic
selector genes are respectively expressed
to determine the polarity and identity of
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