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into the optic tectum of live Xenopus laevis tadpoles
increases the branching of RGC terminals, whereas
blocking BDNF reduces axon arborization (Cohen-
Cory and Fraser, 1995). Altering levels of BDNF in the
retina had no effect on RGC branching in the tectum,
indicating that the branch-promoting effects of BDNF
are local on axon terminals (Lom and Cohen-Cory,
1999; Lom et al., 2002).
The sensory neurons of the dorsal root ganglion
(DRG) provide another example of branching. These
axons enter the spinal cord through the dorsal root and
then bifurcate in to grow in the anterior and posterior
directions. Collaterals then sprout from these branches
to innervate the gray matter of the cord (Ozaki and
Snider, 1997). Using an in vitro assay, it was found
that Slit2 promotes the formation and elongation of
branches in DRG neurons (Wang and Scott, 1999). The
identification of repulsive guidance molecules such as
Slits and Semas, which can control growth cone guid-
ance on the one hand and promote branching on the
other, suggests that there may be a link between re-
pulsion and branching. Indeed, in vitro observations
have indicated that branches form behind the tip of
the growth cone whenever the growth cone collapses
in response to any collapse-inducing agent, even a
mechanical one (Davenport et al., 1999). These obser-
vations are consistent with the finding that the growth
cones of callosal axons in the cortex pause for many
hours beneath their targets prior to the development
of branches (Kalil et al., 2000). Imaging of dissociated
living cortical neurons shows that wherever a growth
cone undergoes a lengthy pause, and then advances
again, filopodial remnants of the paused growth cone
are left behind on the axon shaft (Szebenyi et al., 1998).
Here, the cytoskeleton of the axon appears more
splayed apart and fragmented, and it is from these
regions that new branches form (Dent and Kalil, 2001)
(Figure 6.6). Such results demonstrate that growth
cone pausing is closely related to axon branching.
A
Pathway
Ta r get area
Axon slows and begins to
arborize when it enters tectum
B
C
FGF-2
level
pathway
tectum
Normal axons
entering tectum
pathway and tectum
bathed in FGF-2
Axon keeps on going
FGF-2
level
Axons expressing a
dominant negative
FGF receptor
avoiding tectum
FIGURE 6.5 Growth cones change when they enter their target
zones. A. Images from a time-lapse movie of a retinal ganglion cell
growing in the optic tract and then crossing (at the dotted line) into
the tectum. The simple growth cone becomes much more complex
and slows down dramatically as it enters the target. B. Tectal inner-
vation by control retinal axons (top) and tectal avoidance by retinal
axons that misexpress a dominant negative FGF receptor. C. Retinal
axons slow down and branch when they reach the tectum in control
animals (top), but when the pathway is exposed to high levels
of FGF-2, the axons keep going and do not innervate the tectum.
(Adapted from Harris et al., 1987; McFarlane et al., 1995; McFarlane
et al., 1996)
pathway
tectum
develops, with new branches arising along the stems
of older branches. Many of these new branches are not
tipped with growth cones themselves but appear like
worms wriggling out of the parent branch. What
causes axons to branch in this way? The tectum
expresses the repulsive guidance cue Sema3A.
Sema3A, when applied to retinal growth, cones in
vitro, causes them to collapse, but this collapse is tran-
sient, and recovery from collapse is often associated
with branching (Campbell et al., 2001). Thus, Sema3A
may stimulate terminal branching in the tectum. In
addition, the tectum is a source of BDNF, which also
promotes branching of RGC axons. Injection of BDNF
BORDER PATROL AND PREVENTION
O F INAPPROPRIATE TARGETING
Once they have recognized and entered a target
area, slowed down, and started to branch within,
axons may be prevented from exiting the target area
by repulsive cues at the perimeters. Sema3a, which we
discussed in the last chapter, repels the growth cones
of cutaneous sensory neurons. Analysis of knockout
mice supports a critical role for Sema3a as an exclusion
factor confining the peripheral ends of these axons to
the correct target areas of the skin (Taniguchi et al.,
 
 
 
 
 
 
 
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