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

Cell death i s critical to normal development i n multiple
orga n systems . For example, it is required during
the formatio n of digits and durin g the generatio n of
the middl e ea r spac e an d th e vagina l opening (e.g. ,
Saunders, 1966 ; Rodrigue z et al. , 1997 ; Robert s an d
Miller, 1998) . Likewise, in the central nervous system
(CNS) o f the norma l developin g mammal , a n esti -
mated 20%-80 % mor e neuron s than th e final num -
ber ar e generate d befor e th e surplu s i s eliminate d
(Miller, 1995 ; Sastry and Rao , 2000). This loss of neurons
varies by brain structure an d b y specific neuro n
populations.
In som e brai n structure s there i s a wholesale loss
of transien t neurona l populations . Suc h cullin g o f
populations i s required for proper developmen t t o ensue.
Two exemplary populations ar e subplate neuron s
(e.g., Kostovic and Rakic, 1980 ; Chun et al., 1987 ; Al-
Ghoul and Miller, 1989) , and Cajal-Retziu s neuron s
(e.g., Dere r an d Derer , 1990 ; Meye r e t al., 1998 ) i n
neocortex (Marin-Padilla , 1998 ; Supe r e t al. , 1998 ;
Sarnat an d Flores-Sarnat , 2002) . I t i s believe d tha t
6
Intracellular Pathway s
of Neuronal Death
Sandra M. Moone y
George I. Henderson
91
these populations die after they serve their role in cortical
development . Th e subplat e neuron s provid e a
temporary targe t populatio n fo r thalamocortica l ax -
ons that arriv e i n the subplat e befor e the neuron s of
their target layer (cortical layer IV) have migrated t o
their final position (Ghosh e t al., 1990) . Cajal-Retzius
neurons expres s reelin, which i s vital for normal mi -
gration of cortical neurons (Lambert de Rouvroit and
Goffinet, 1998 ; Rice and Curran, 2001). This association
is indicated b y the disrupted cortical organization
that occur s i n reeler mic e (Lamber t d e Rouvroi t and
Goffinet, 1998 ) an d whe n Cajal-Retziu s neurons are
prematurely los t (Frotscher , 1998 ; Hartman n e t al. ,
1999; Saftigetal, 1999) .
Target-dependent neurona l deat h ma y b e th e
most important proces s controlling neurona l deat h in
the CNS . Throug h thi s mechanis m th e nervou s system
sculpts itself , matching th e number o f neurons in
communicating part s o f a syste m fo r optimal outpu t
and maximizin g efficien t function . Neurona l deat h
occurs i f (a ) ther e i s a lac k o f input/innervation ,