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Limb bud
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limb bud
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limb bud
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DRG neurons
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DRG neurons
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motor neurons
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motor neurons
FIGURE 7.9 The amount of target tissue influences neuron survival. Two experimental strategies have
been used to test whether target tissue provides neurons with a survival factor. In the embryonic chick, a
limb bud can be surgically removed, or an extra limb bud can be grafted nearby. The animal is then per-
mitted to progress through the time when cell death would normally occur. (Left) When a limb bud is
removed, the process of cell death is enhanced, and there are fewer motor neurons and DRG cells. (Right)
When an extra limb bud is grafted on, the process of cell death is decreased, and there are a greater number
of motor neurons and DRG cells. (Adapted from Hamburger, 1943; Hollyday and Hamburger, 1976)
than normal numbers (Hamburger, 1943; Hollyday
and Hamburger, 1976).
Acomplementary experiment can be performed by
reducing the number of neurons projecting to a target,
and determining whether the remaining cells died off
anyway. In one such experiment, about two-thirds of
the ciliary ganglion neurons innervating one eye are
killed off by cutting their axons. After the normal
period of cell death has ended, the number of ganglion
cells remaining is almost 40% greater than expected.
Furthermore, several of the surviving axons sprout
into the peripheral territory that is vacated by the
death of axotomized ciliary neurons. Therefore, par-
ticular neurons are not preordained to die but appear
to do so through some sort of competition for a feature
of the target (Pilar et al., 1980).
A basic question that arises from these studies is
whether the target influences neuron proliferation or
cell death. By carefully studying the pattern of degen-
eration of DRG neurons following wing bud removal
in the chick, Viktor Hamburger and Rita Levi-Montal-
cini (1949) demonstrated that target removal leads to
an increase in the number of dying neurons. One wing
bud was removed at about 3 days of incubation, and
the dorsal root ganglia were examined ipsilateral and
contralateral to the ablation. Within 2-3 days, the
ganglia ipsilateral to the extirpated wing buds were
much smaller than normal and contained a large
number of darkly stained pyknotic cells (Figure 7.10).
Although they also reported the number of mitotic
cells to vary with target size, subsequent studies show
that target removal has little or no affect on the amount
of tritiated-thymidine incorporated into DRG neurons
(Carr and Simpson, 1978).
The concept of target-dependence extends to the
earliest period of maturation, well before growth cones
have reached their synaptic target. During embryonic
development, commissural neurons in the dorsal
spinal cord are attracted to the floorplate where they
eventually cross the midline (see Chapter 5). The floor-
plate region also appears to provide a survival signal.
When E13 commissural neurons are are grown in vitro,
they all die within 2 days, but they can survive for
several days when grown in the presence of floorplate-
conditioned medium (Wang and Tessier-Lavigne,
1999). In the zebrafish, the death of vental primary
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