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

82 NORMA L DEVELOPMENT
FIGURE 5-6 Aneuploi d neural progenitor cell s (NPCs )
in the embryonic mouse brain. A. Spectral karyotyping
(SKY) fro m a representativ e aneuploi d embryoni c
NPC. Spectra l (left) an d invers e DAPI (center) images
of the chromosom e sprea d are shown, along with th e
karyotype table (right) . Not e that each differen t chro -
mosome ha s a uniqu e spectra l colo r (indicate d b y
shades of gray). Euploid chromosome numbe r i n mic e
aneuploidy impart s diversity and complexit y t o neu -
ronal populations , an d tha t aneuploi d NPC s ar e
selected o n the basi s of their genomic contents , with
one probable fate being cell death. The pervasiveness
of adul t neura l aneuploid y may indicat e a selective
advantage acquire d b y som e aneuploi d neurons , a s
has bee n note d i n certai n aneuploi d cance r cell s
(Lengauer e t al , 1997) . Thus , variatio n in chromo -
some numbe r can b e considere d a new mechanis m
for generating cellular diversity in the CNS .
The main conclusion from these data is that aneuploid
cells are found in the developing and adult ner -
vous system, demonstrating tha t brain cells can diffe r
at th e leve l o f thei r genome . Whethe r DN A re -
arrangements are als o present i n thes e cell s remains
an ope n question . Thes e somati c change s i n th e
DNA of a cell could affec t a significant portion of the
genome, alterin g hundred s o f gen e copie s whic h
would hav e important consequences fo r the physiol -
ogy of that cell. The globa l effect o f this process could
is 40. The sprea d has an extr a copy of chromosome 2 ,
but ha s only one cop y of chromosomes 1 5 and 1 7 (39,
XY, +2, -15, -17). B . Graphs show the percentage of
loss (left ) an d gai n (right) of specific chromosome s i n
NPCs. Bar s are coded o n th e basi s of spectral color of
each chromosome (excep t for sex chromosomes). Spe -
cific chromosome s ar e los t a t rate s o f 1.6%—8.4 % o f
cells analyzed and are gained at rates of less than 2%.
result in a mature brai n that i s a unique genetic mosaic,
characterize d b y a euploi d populatio n inter -
mixed with a diverse aneuploid population of neurons
(Rehen e t al , 2001 ; Kausha l e t al , 2003 ; Yang et al ,
2003).
LYSOPHOSPHATIDIC ACID,
CELL CYCLE EXIT, DECREASED
PROGRAMMED CELL DEATH, AND
INCREASES IN BRAIN DIMENSION S
A variety of extracellular factors hav e been show n to
influence NPC s an d youn g neuron s o f th e cortex .
Neurotransmitters (LoTurco et al., 1995 ) and peptid e
factors (Drag o e t al. , 1991 ; Ghos h an d Greenberg ,
1995; Temple and Qian , 1995 ) affect neurogeni c parameters
o f developin g cortica l cells , althoug h i t i s
generally unclea r ho w thes e signal s influenc e th e
growth and morpholog y of the intac t cerebral cortex.