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1.2 The Cerebral Cortex
1.2.1 Development of the Cerebral Cortex In Vivo
Among the various telencephalic regions, the cerebral cortex is the center of human-
specific integral neural activity. The cerebral cortex exhibits a highly complex struc-
ture, which is characterized by a six-layered laminar structure (Northcutt and Kaas
1995 ). This complex structure is established through precisely designed processes,
including cell proliferation, differentiation, and migration (Kriegstein et al. 2006 ;
Kriegstein and Noctor 2004 ). During the early stages of cortical development, corti-
cal neuroepithelial (NE) cells are located in the ventricular zone (VZ) facing the
ventricle and form a highly polarized, pseudostratified layer structure (Huttner and
Brand 1997 ) (Fig. 1.2). They first self-renew by symmetric divisions, and then they
convert into neurogenic apical progenitors (called radial glia) (Noctor et al. 2001 ;
Miyata et al. 2001 ). Apical progenitors, which possess an apical process to the pial
surface, generate cortical pyramidal neurons by asymmetric divisions either directly
or through transit progenitors (called intermediate progenitors; Tbr2+) in the sub-
ventricular zone (SVZ) (Noctor et al. 2004 ). Different types of cortical pyramidal
neurons are born in a sequential order from these progenitors and migrate along the
apical process of the progenitors to the pial surface (Kriegstein and Noctor 2004 ).
Then, the newborn neurons settle in the appropriate laminae of the cortical plate in
an inside-out manner (in which late-born neurons migrate to more superficial layers
than early-born neurons) (Angevine and Sidman 1961 ). Finally, the cortical plate
forms six neuronal layers that differ markedly in gene expression, physiological
aspects, and projection patterns (Molyneaux et al. 2007 ). The pyramidal neurons are
glutamatergic/excitatory neurons, and they comprise the majority (approximately
80%) of cortical neurons. GABAergic/inhibitory neurons, comprising approxi-
mately 20% of the cortical neurons, originate from the ventral telencephalon and
then migrate tangentially to the cortex and integrate into the network (DeFelipe
et al. 2002 ).
The mammalian cortex can be divided into several areas, such as visual or motor
areas, which have distinct anatomy and function (Wree et al. 1983 ). Two models of
the mechanism that controls cortical arealization have been proposed from mouse
studies: the protomap model and the protocortex model. The protomap model pos-
tulates that cortical arealization is patterned by the graded expression of certain
transcriptional factors in apical progenitors at early stages (Rakic 1988 ; Sansom
et al. 2005 ). The protocortex model postulates that cortical arealization is patterned
by the thalamocortical axon (TCA) inputs at later stages (O’Leary 1989 ). These
mechanisms are not mutually exclusive; they may play complementary roles for
rigorous regulation (Sur and Rubenstein 2005 ).
The basic mechanisms of corticogenesis seem to be conserved in the mammalian
cortex, but the primate cortex exhibits distinct features compared with rodent cortex
(Smart et al. 2002 ). The most striking histological difference is the thickness of the
T. Kadoshima et al.