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Yolk sac
Sympathetic ganglia
Dorsal root ganglia
FIGURE 7.11 A target-derived soluble factor can support neuron survival. A. When a tumor cell line is
placed in the chick embryo at E3, the size of sympathetic ganglia and DRGs is much larger ipsilateral to the
tumor by E7. (B) When the same tumor cell line is placed on the chorioallantoic membrane at E3, such that
nerve fibers have no direct access, all of the symapthetic and dorsal root ganglia are much increased in size
by E7. Thus, the tumor must have secreted a soluble factor that enhanced neuron survival. (Adapted from
Bueker, 1948; Levi-Montalcini and Hamburger, 1951; Levi-Montalcini and Hamburger, 1953)
employed. Snake venom was known to contain high
levels of an enzyme that breaks down nucleic acids
(phosphodiesterase). Therefore, it was added to the
extract to determine whether this class of molecules
mediated the trophic effect (Cohen and Levi-Montal-
cini, 1956; Levi-Montalcini and Cohen, 1956). If the bio-
logical activity was lost, then one could conclude that
growth factor contained nucleic acids. Surprisingly,
the tumor fraction containing the snake venom was
even more potent than the origin protein-nucleic acid
fraction. Even more curious, the snake venom itself
was found to support nerve growth (Figure 7.12).
As it turned out, the discovery of a growth-pro-
moting effect in snake venom was extremely fortunate.
It suggested that growth-promoting activity would
also be found in a mammalian analog, the salivary
gland. In fact, the mouse submaxillary gland proved
to be a wonderful source for the Nerve Growth Factor,
and this eventually led to its complete isolation and
Once the NGF was purified, it was possible to
perform two critical experiments in vivo to determine
whether this protein is both necessary and sufficient to
keep sensory and sympathetic neurons alive during
development. First, the NGF protein that was purified
from snake venom was injected directly into neonatal
rodents, and it did produce a dramatic increase in the
size of sensory and sympathetic ganglia (Levi-Montal-
cini and Cohen, 1956). In addition to keeping neurons
alive, it is also clear that NGF promotes process out-
growth. For example, when NGF is injected into
neonatal rodents, sympathetic nerve fibers are no
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