Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1208 Chapter 21: Development of Multicellular Organisms
(A)
wild-type neuron
wild-type
neuron
wild-type neuron
mutant
neuron
lacking
DSCAM1
neurons
expressing
single DSCAM1
isoform
Figure 21–80 DSCAM mediates selfavoidance
of dendrites. (A) Sensory
neurons in the Drosophila peripheral
nervous system extend dendrites along
the larval body wall. The image shows the
dendrites of a regular array of photosensing
neurons (red), which allow the larva
to detect and avoid harmful light. The
posterior epidermal cells of each segment
are labeled in blue. There are many
neurons, and those shown here spread
out their dendrites into overlapping fields.
(B) Mutations at the Dscam locus upset
the way the various dendrites interact,
changing the rules of self-avoidance and
the distribution of innervation. (A, courtesy
of Chun Han; B, after D. Hattori et al.,
Annu. Rev. Cell Dev. Biol. 24:597–620,
2008. With permission from Annual
Reviews.)
red dendrites repel each
other and blue dendrites
repel each other; but
blue and red do not
repel each other
(B)
red dendrites repel
each other; but orange
dendrites repel neither
themselves nor red
dendrites
green dendrites repel
each other
Target Tissues Release Neurotrophic Factors That Control Nerve
Cell Growth and Survival
Eventually, axonal growth cones MBoC6 reach n22.238/22.81
the target region where they must halt and
make synapses. These synapses, as a rule, are destined to transmit neural signals
in one direction, from axon to target cell. The development of synapses, however,
depends on signaling in both directions: signals from the target tissue not only
help control which growth cones synapse where (as we discuss shortly), but can
also regulate how many of the innervating neurons survive.
Many types of vertebrate neurons are produced in excess; up to 50% or more of
some of them die soon after they reach their target, even though they appear perfectly
normal and healthy up to the time of their death. About half of all the motor
neurons that send axons to skeletal muscle, for example, die within a few days
after making contact with their target muscle cells. A similar proportion of the
sensory neurons that innervate the skin die after their growth cones have arrived
there.
This large-scale normal neuronal death often seems to reflect the outcome of
a competition, in which the target tissue releases a limited amount of a specific
neurotrophic factor that the neurons innervating the tissue require to survive;
those that do not get enough die by programmed cell death. If the amount of target
tissue is increased—for example, by grafting an extra limb bud onto the side
of the embryo—more limb-innervating neurons survive; conversely, if the limb
bud is cut off, the same neurons all die (Figure 21–81). In this way, although individuals
may vary in their bodily proportions, they always retain the right number
of motor neurons to innervate all their muscles and the right number of sensory
neurons to innervate their body surface. The strategy of overproduction followed
by death of surplus cells may seem wasteful, but it provides a simple and effective
means to adjust the number of innervating neurons according to the amount of
tissue requiring innervation.
The first neurotrophic factor to be identified, and still the best characterized,
is called nerve growth factor (NGF )—the founding member of the neurotrophin
family of signal proteins. It promotes the survival and growth of specific classes of
sensory neurons and of sympathetic neurons (a subclass of peripheral neurons
that control contractions of smooth muscle and secretion from exocrine glands).