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

16 NORMA L DEVELOPMEN T
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FIGURE 2- 4 Spatiotempora l gradient s o f cell proliferatio n and neurogenesi s i n th e cerebra l cortex .
Neurogenesis in the cerebra l cortex progresses along tangential (A ) and radia l (B) gradients. A. Neo -
cortical neurogenesi s begin s at the rostroventrolatera l regio n o n gestationa l da y (G) 1 1 in mice an d
proceeds toward the caudodorsomedial regio n in a systematic gradient (curved arrow). This transverse
neurogenetic gradien t translates into a corresponding gradient in cel l cycle length o f the precursor
population an d the probability of cell cycle exi t (Q) for the daughte r cells . Thus, precursor cell s in
the pseudostratifie d ventricula r epithelium (PVE ) i n the rostroventrolatera l region have longer cell
cycle time and highe r values of Q compare d to their counterparts in the caudodorsomedial region.
B. Neurogenesis als o proceeds alon g a radial gradient. Neurons of the deep layers are produced ear -
lier than those in the superficial layers. Each neocortica l PVE cell in mice, on average, undergoes 1 1
cell cycles over a 7-day period from Gil to G17. Cell cycle length increase s with each cell cycle and
each cycle is associated with a unique value of Q. Thus, the cel l cycle length increase s from abou t 8
to 1 8 hours over the cours e o f 1 1 cell cycles . The valu e of Q increase s from abou t 0. 1 t o 0.8 , ap -
proaching the maximal value of 1.0, during this interval and reaches the halfway mark (0.5) betwee n
cell cycle s 7 and 8 on G1 4 (broken line an d asterisk) . Each cel l cycl e produces cell s destine d fo r
specific neocortical layer(s). Thus, cell cycle number, cell cycle length, Q, and layer destination are
linked to one another during normal development. (Source: Base d on data of Takahashi et al., 1999 ;
Tarili et al., 2005)
layer wa s the n develope d b y Takahash i an d col -
leagues (1999) . Theoretically , neuron s produce d a t
any time point during the neurogenetic sequenc e ca n
have som e probabilit y of occupying any neocortica l
layer. I n reality , however , durin g norma l develop -
ment neuron s generate d durin g cel l cycl e 1 hav e
nearly a 100 % probabilit y of occupying laye r VI an d
0% probability of occupying layer II—III, and neuron s
generated durin g cel l cycl e 1 1 (th e fina l cel l cycle )
have a near 100 % probability of occupying layer II—III
and 0 % probabilit y of occupyin g laye r VI . Sinc e a
given cell cycle number is associated with given values