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FIGURE 5.27 Growth cone collapse. A time-lapse series of a
growth cone from a retinal ganglion cell encountering an axon of a
sympathetic axon in culture. Upon first contact, the growth cone
retracts and collapses. (From Kapfhammer and Raper, 1987a)
FIGURE 5.28 Sema3A is repulsive to pain fibers of the DRG.
A. A DRG (left) is plated next to a small clump of COS cells (right)
that are transfected with the Sema3A gene. NGF is added to the
medium so that pain fibers grow out. There are few neurites, and
most of these grow away from the COS cells. B. In a control exper-
iment with untransfected COS cells, the DRG puts out neuritis in all
directions. (After Messersmith et al., 1995)
kin et al., 1993), was originally named FasciclinIV
because it is expressed on particular axon fascicles.
Semal is also expressed in stripes near segment borders
on the limb bud epithelium, and antibodies that neu-
tralize SemaI function in the limb allow the Ti1 pio-
neers to cross the segment border, suggesting that this
molecule normally serves a repellent function.
Sema3A is responsible for the repulsive guidance of
DRG axons in the ventral spinal cord, described above.
Sensory neurons that carry information from pain
receptors to the CNS grow into dorsal roots of the
spinal cord and synapse locally with dorsal inter-
neurons, avoiding the more ventral spinal cord. Both
ventral spinal cord and COS cells made to express
Sema3A are able to repel these pain neurons (Messer-
smith et al., 1995) (Figure 5.28). In Sema3A knockout
mice, however, the axons of these neurons enter the
ventral spinal cord. In contrast, afferents from stretch
receptors dive ventrally to synapse on motor neurons
in normal animals and are not repelled by Sema3A.
These results suggest that the family of Semaphorin
signals is specifically arranged in the CNS to repel spe-
cific axons, presumably those that have receptors to
particular family members. The ectoderm, dermomy-
otome, and notochord, it turns out, also repel DRG
axons (Figure 5.26E, F). If a DRG is placed between a
dermomyotome and a piece of notochord in a collagen
gel, mimicking its in situ position between these
tissues, the result is bipolar axon growth that looks
very much like the in vivo trajectory of these neurons
and suggests that “surround repulsion” may be a key
mechanism for shaping the process trajectories of the
developing neurons (Keynes et al., 1997).
An interesting wrinkle concerning repulsive guid-
ance is that the receptor for this cue must first bind the
repellent molecule before turning away from it. Since
the specificity is often high, this means that the affinity
between the receptor and the repellent molecule is also
strong. This may not be a problem if the repulsive cue
is in the form of a diffusible gradient, but often repel-
lent molecules are attached to cell membranes or the
ECM. In such cases, one might imagine that if the affin-
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