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DRGs that innervate axial musculature. The DRGs that
innervate wings and legs have more tissue to inner-
vate, and the amount of cell death is much reduced in
these ganglia. The central and peripheral projections
of DRG neurons make contact with their target before
cell death occurs. Therefore, naturally occurring cell
death does appear to be an important mechanism
for thinning out neuron populations with less target
to innervate (Ernst, 1926; Hamburger and Levi-
Montalcini, 1949).
There is only one system in which cell death has
been quantified in both the pre- and postsynaptic neu-
ronal population (Figure 7.8). This provides a natural
situation in which to ask whether a decrease in the
target population is correlated with cell loss in the
innervating neurons. The presynaptic population of
cells, called nucleus magnocellularis (NM), is the first
region of the chick brain to receive input from the ear,
and these cells project to a second-order auditory
nucleus, called nucleus laminaris (NL). Both groups of
cells undergo their final mitosis, migrate to their final
positions, and begin a period of normal cell death that
occurs primarily from embryonic day 11 to 13. The
percentage of cells that die in the two nuclei is quite
similar. About 18% of the presynaptic NM neurons die
during this interval, while 19% of the postsynaptic NL
neurons are wiped out (Rubel et al., 1976; Solum et al.,
1997). However, cell death occurs more rapidly in NM
than in NL, as highlighted by the bar at 11-13 days
(Figure 7.8). Thus, although the magnitude of cell
death is well-correlated in these two interconnected
cell groups, the relative timing suggests that target size
is not the sole determinant of neuron survival.
Even before normal cell death was a well-accepted
event, it was known that developing nerve cells died
when their target was removed. A common manipula-
tion was to remove a limb bud prior to the time of
innervation (i.e., no direct damage to the axons) and
then examine the motor neurons or DRG cells that
would have made synapses there. These studies were
performed on amphibian or chick embryos because it
was relatively easy to carry out the surgeries. The
removal of an appendage was usually devastating to
the pool of presynaptic neurons (Figure 7.9). In the
salamander, Amblystoma , the sensory ganglia that
normally innervate a limb are much smaller when the
limb is excised. In contrast, sensory ganglia that nor-
mally innervate axial musculature are much larger
than normal if provided with a transplanted limb
(Detwiler, 1936).
The relationship between motor neuron number
and target size is remarkably linear in the chick. As
greater and greater amounts of muscle are removed
from developing chick embryos, the ventral horn of
Days from emergence of hind limbs
FIGURE 7.6 The period of cell death in frog motor neurons. The
graph shows the total number of healthy (black) and pyknotic (red)
motor neurons that innervate the frog hind limb during each of
several developmental stages. At the top is a picture of leg size
during this period. The number of pyknotic (degenerating) neurons
reaches a peak at precisely the time when the loss of healthy (viable)
neurons is most rapid, as indicated by the bar. (Adopted from
Hughes, 1961)
neurons in the limb region of its spinal cord which then
proceed to die during development (Raynaud et al.,
1977). Therefore, neurogenesis provides a primary point
of regulation for setting neuron number (see Chapter
3), and cell death provides a second. This concept is
raised again when we discuss the overproliferation
and elimination of synaptic contacts (see Chapter 9).
In fact, cell death has been suggested as one way to get
rid of extra synapses during development.
If apoptosis is a developmental mechanism for
matching the size of a presynaptic population to its
target, then it should occur at a discrete time and place.
This was explored in dorsal root ganglia (DRG), where
about 30% of neurons die during normal development
(Figure 7.7). The first observation is that neurons die
during a specific time interval. In the chick, DRG
neurons begin to degenerate at embryonic day 4.5, and
this continues for 2 1 / 2 days. The second observation is
that natural cell death occurs predominantly in those
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