Brain Development: Normal Processes and the Effects of Alcohol ...

of Q, anothe r wa y of interpreting these finding s i s that
the probability that a cell arising from a given cell cycle
will occupy a specific laye r is tightly linked t o the values
of Q. Lower Q values predict destination to deeper
layers and higher values predict destination t o more superficial
layers. What factors set the probability values?
Overexpression of the cd k inhibitor p27 ki P* in th e
PVE increases Q, and that the neurons produced during
the cell cycles with the experimentally elevated Q
values assum e superficia l lamina r position s tha t
would be appropriate for the higher value of Q (Tarui
et al. , 2005) . Therefore , Q an d lamina r destinatio n
appear t o b e highl y correlated . Also , thes e finding s
suggest that p27 kl P* expression and activit y play a role
in setting the value s of Q. Recen t dat a sho w that an -
other cdk inhibitor, p21, is also involved in cell cycle
exit (Siegenthaler an d Miller , 2005) . Furthermore, a
variety of genetic and environmenta l factors , such as
transcription factors , growt h factors , an d neurotrans -
mitters, influenc e intracellula r p27 ki P J an d p21 wofl
content. Th e combine d action s o f these factor s ma y
regulate Q and , therefore , neocortica l neurona l fat e
during normal development .
The discussio n above pertains directly to the regulation
o f cel l proliferatio n i n th e neocortica l PVE .
Neocortical neuron s aris e not only from the neocorti -
cal PVE but also from the proliferative cells in the GE .
Neocortical PV E i s the sourc e o f neocortica l (gluta -
matergic) projection neurons (PNs), which constitut e
70%-90% o f al l neocortica l neuron s (Peter s e t al ,
1985; Re n e t al, 1992 ; Beaulieu , 1993) . I n rodents ,
the majorit y o f GABAergi c loca l circui t neuron s
(LCNs) o f th e cerebra l cortex , whic h constitut e
10%-30% o f all neocortica l neurons , i s produced i n
the media l an d cauda l GE s o f th e basa l forebrai n
(Anderson et al, 1997a ; Tamamaki e t al, 1997 ; Lavdas
et al, 1999 ; Powel l et al., 2001; Nery et al., 2002;
Ang et al, 2003). These LCNs arrive in the cerebra l
cortex via tangential migrator y pathways. In primates ,
however, i t appear s tha t mos t GABAergi c LCN s o f
the cerebra l corte x derive from th e neocortica l PV E
and only a minority come from the GÈ (Letinic et al.,
2002). Although neocortica l PN s and LCN s ar e produced
i n different locations , both types of neurons located
i n th e sam e neocortica l laye r appea r t o b e
produced o n the same day, at least in rodents (Miller ,
1985, 1988b ; 1999 ; Fairé n e t al, 1986 ; Goba s an d
Fairén 1988 ; Valcanis and Tan, 2003).
Neocortical gli a ar e generate d i n th e SP P
(Smart, 1961 ; Smar t an d LeBlond , 1961 ; L e Vine
CELL PROLIFERATION 1 7
and Goldman, 1988a , 1988b ; Levison and Goldman ,
1993). One notabl e exception to this pattern is that of
radial glia , which commonl y hav e cel l bodie s i n th e
PVE, an d may undergo transformation into astrocytes
near th e en d o f th e neuronogeneti c epoc h (Voigt ,
1989; Takahash i e t al , 1990 ; Misso n e t al , 1991 ;
Miller an d Robertson , 1993) . A distinguishable SP P
(SZ) appear s i n th e neocortica l proliferativ e regio n
soon afte r th e first cortical neuron s are generated, b y
G13 i n th e mous e (Miller , 1989 ; Takahash i e t al,
1995). At this time, th e siz e of the SP P is