The Questions of Developmental Biology

The activity of the synapse releases N-cadherin from storage vesicles in the growth cone
(Tanaka et al. 2000).
After the first contact is made, growth cones from other axons converge at the site to
form additional synapses. During development, all mammalian muscles studied are innervated by
at least two axons. However, this polyneuronal innervation is transient. During early postnatal
life, all but one of these axon branches are retracted. This rearrangement is based on
"competition" between the axons (Purves and Lichtman 1980; Thompson 1983; Colman et al.
1997). When one of the motor neurons is active, it suppresses the synapses of the other neurons,
possibly through a nitric oxide-dependent mechanism (Dan and Poo 1992; Wang et al. 1995).
Eventually, the less active synapses are eliminated. The remaining axon terminal expands and is
ensheathed by a Schwann cell.
Differential survival after innervation: neurotrophic factors
One of the most puzzling phenomena in the development of the nervous system is
neuronal cell death. In many parts of the vertebrate central and peripheral nervous systems, over
half the neurons die during the normal course of development (see Chapter 6, especially Figure
6.28 ). Moreover, there do not seem to be great similarities across species. For instance, in the cat
retina, about 80% of the retinal ganglion cells die, while in the chick retina, this figure is only
40%. In the retinas of fishes and amphibians, no retinal ganglion cells appear to die (Patterson
1992).
The apoptotic death of a neuron is not caused by any obvious defect. Indeed, these
neurons have differentiated and successfully extended axons to their targets. Rather, it appears
that the target tissue regulates the number of axons innervating it by limiting the supply of a
neurotrophin. In addition to their roles as chemotrophic factors (see above), neurotrophins have
been shown to regulate the survival of different subsets of neurons (Figure 13.26). NGF is
necessary for the survival of sympathetic and sensory neurons.
Treating mouse embryos with anti-NGF antibodies reduces the number of trigeminal
sympathetic and dorsal root ganglion neurons to 20% of their control numbers (Levi-Montalcini
and Booker 1960; Pearson et al. 1983). Removal of these neurons' target tissues causes the death
of the neurons that would have innervated them, and there is a good correlation between the
amount of NGF secreted and the survival of neurons that innervate these tissues (Korsching and
Thoenen 1983; Harper and Davies 1990). BDNF does not affect sympathetic or sensory neurons,
but it can rescue fetal motor neurons in vivo from normally occurring cell death and from induced
cell death following the removal of their target tissue.