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

Over the pas t several decades, the importanc e of cell
death i n the formation of the nervou s system has become
wel l established . Indeed , understandin g cel l
death i n th e developin g brai n ha s been on e o f th e
most exciting areas of research in neuroscience. Th e
present chapter focuses on the mammalian fetal cerebral
cortex as a paradigm of study.
HISTORICAL RECOGNITION O F
PROGRAMMED CELL DEATH
AND APOPTOSIS
Embryologists hav e lon g recognize d tha t regressiv e
events play a major role in shaping organ development
(Clarke an d Clarke , 1996) . Abou t S O years ago , th e
term programmed cell death (PCD ) wa s coined . I t
evolved from detaile d studie s of the cellula r degenera -
tion durin g insec t metamorphosi s (Lockshi n an d
Williams, 1965 ) and the morphogenesis o f avian limbs
(Saunders, 1966) . PC D i s a geneticall y regulate d
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Cell Death
Stevens K. Rehen
Jerold J.M. Chun
73
mechanism that plays a critical role in specifi c stages
of development, sculptin g different organ s during the
formation an d maturatio n o f tissue s (Elli s e t al. ,
1991).
Apoptosis is the bes t known form o f PCD, charac -
terized originally by morphological change s observe d
by microscopy (Kerr et al., 1994). Apoptosis is characterized
by nuclear size reduction, blebbing of the cel -
lular membrane, chromatin condensation , and DNA
fragmentation (Ker r et al, 1972 ; Wyllie et al, 1984) .
In the absence of inflammation, the apoptotic corpses
are usuall y eliminate d b y phagocytes (Arend s e t al,
1990), whic h us e th e phosphatidylserin e recepto r
(PSR) to identify and remove the dying cells (Zhuan g
et al, 1998 , Wan g e t al, 2003) . Apoptosis is considered
a counterpoin t t o cel l deat h b y necrosi s (Ker r
et al. , 1972) . Necrosi s i s distinguishe d b y earl y
swelling and ruptur e o f both intracellula r organelle s
and the plasma membrane.
Although th e definitio n o f apoptosi s i s based o n
morphological criteri a and PC D i s characterized as