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Apoptotic bodies
Pyknosis (apoptotic figures)
cross-linking of proteins
FIGURE 7.5 Dying cells in the proliferative zone. A. Two micro-
graphs of the embryonic day 18 mouse cortex. To the left, apoptotic
cells are labeled with a technique similar to TUNEL, called ISEL. To
the right, all cells are revealed with fluorescent labeling of nuclei.
Note the prominent ISEL labeling in the ventricular zone where pro-
liferation occurs (cp, cortical plate; iz, intermediate zone; vz, ven-
tricular zone) (Blaschke et al., 1996). B. An electron micrograph from
the ventricular zone of an E16 rat cerebral cortex shows a cell with
the histological features of apoptosis. The inset shows a TUNEL-
positive cell in the subventricular zone of a newborn rat (LV, lateral
ventricle) (Thomaidou et al., 1997).
FIGURE 7.3 A comparison between apoptosis and necrosis.
Naturally occurring cell death is usually accomplished through a
process called apoptosis . During apoptosis, the neuron begins to
shrink, and the nuclear matter becomes condensed, forming cres-
cent-shaped figures. As proteins become cross linked at the mem-
brane, small apoptotic bodies break off and are phagocytized. In
contrast, injured neurons tend to die through a process of necrosis .
During necrosis, the mitochondria stop functioning, and neurons
cannot maintain an osmotic balance. The cell swells up, undergoes
autolysis, and finally bursts open.
within two weeks of birth, and a 50% loss is observed
in embryonic chick ciliary ganglion after the neurons
have projected to the iris and choroid (Potts et al., 1982;
Landmesser and Pilar, 1974). While it is impractical to
count the total number of neurons in any one area of
cerebral cortex, it is estimated that 20 to 50% of post-
migratory neurons are eliminated. However, this may
depend on the type of cell, the region of cortex, and the
time of birth (Miller, 1995; Finlay and Slattery, 1983).
dUTP-biotin ( )
FIGURE 7.4 During apoptosis, DNA is broken down by endonu-
clease activity to produce double-stranded, low-molecular-weight
fragments. These DNA fragments can be detected by a labeling tech-
nique called TUNEL. A modified nucleotide, such as dUTP-biotin,
is catalytically attached to the free 3ยข-hydroxyl end of each DNA
fragment by the enzyme, terminal deoxynucleotidyl transferase.
Therefore, the nuclei of dying neurons can be detected before the
cells break up and are phagocytosed.
pyknotic cells (Figure 7.6). At first glance, it may not be
clear why so few pyknotic neurons are observed
during the period of maximal neuron elimination. This
is due to the rapid removal of cell debris, which has
been variously estimated to occur in as little as 3 hours.
The magnitude of cell death is impressive. The data
in Figure 7.6 show that the motor neuron population
innervating frog hind limbs declines from an initial size
of about 4000 to a final size of 1200. Thus, well over half
of the differentiated motor neurons are eliminated
from the nervous system. A similar amount of cell
death has been detected at all levels of the nervous
system. About 50% of rat retinal ganglion cells die
The overproliferation of neurons in most areas of
the CNS suggests that it is a valuable mechanism. It
has been suggested that cell death ensures that the
number of afferents is well matched to the size of the
target population. This theory makes the rational
assumption, known to every woodworker, that it is
easier to trim off the excess than to paste on a little
bit extra later. Thus, we would expect a far greater
number of motor neurons to innervate the bulky leg
muscles of an elephant than would innervate the short,
skinny legs of a mouse. There are many interesting
examples of this principle, such as the limbless lizard,
Anguis fragilis , that does produce a set of motor
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