Neuroscience
Online
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Section I:
Cellular and Molecular Neurobiology
9. Synapse Formation/Survival/Elimination
Part 2 of 10
Andrew J. Bean, Ph.D.
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Sources
of Guidance Information
Axonal growth cones serve to sense enviornmental cues and direct the movement
of axons in their quest to make synapses with their targets. Guidance cues are
necessary to control the growth of axons for long distances to precise destinations.
The molecular mechanisms by which these cues act probably involve altering the
rate or location of actin polymerization by acting on receptors on the growth
cone surface, that are linked to intracellular signaling cascades.
Guidepost cells
Axonal trajectories appear to be broken up into a series of smaller movements.
The axon finds intermediate targets that act as choice points. Axons slow
and transform their morphology at these points, and apparently look for
another round of directions. Pioneering growth
cones (the growth cones on initial axons that are later joined by other
axons to create a large axon bundle) are thought to be influenced by these
intermediate targets (called guidepost cells
in insects). The pioneering growth cones are also influenced by other cues
such that the intermediate targets exert only one of a number of influences
on the path of growing axons. |
Figure 9.5
Guidepost cells act as intermediate targets to help guide
growth cones to their final targets.
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Fasciculation
| The bundling together of axons into tracts is called fasciculation. Axonal fasciculation is also a guidance
cue as segments of some axonal trajectories migrate along preexisting axon
tracts. Thus, axons may follow the pathways laid down by the pioneering
axons, although there is some selectivity. An axon may pass a number of
axon tracts and make specific choices about which of these axon tracts to
follow. It is not yet clear whether the pioneer cells are absolutely required
for pathfinding in follower cells. If pioneer cells are not present, the
follower cells are more prone to make pathfinding errors, although these
errors are largely corrected and the axons find their targets. |
Figure 9.6
Axon fasciculation. The pioneer axon (blue) serves as
a scaffold for the outgrowth of the new axon from another cell (purple).
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Guidance Forces
- Local vs. long range
- Attraction vs. repulsion
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Target derived signals
Guidepost cells and preexisting axons can affect the outgrowth of developing axons.
In addition to these influences, axons also receive long-range guidance information.
This short- or long-range guidance information can be attractive or repulsive
and serves to push or pull the growth cone in the correct direction towards its
target.
Short-range guidance mechanisms, like the interaction with guidepost cells
and fasciculation, involve contact-mediated detection by the growth cone filopodia.
This contact may be attractive or repulsive. Long- range, diffusable factors
may also influence axonal guidance by both attraction and repulsion. It is likely
that axons are affected by both local and long-range forces acting simultaneously.
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Attractive forces produced by diffusable factors, serve to direct axons
to their appropriate targets.
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Repulsive signals, in the form of concentration gradients of soluble
proteins, help to direct axons away from incorrect destinations.
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Target Recognition-Topographic Maps
Axonal projections are often topographically organized, such that neighboring
neurons in the region of origin project to neighboring neurons in the target region
(e.g., retinal ganglion cells project topographically onto neurons in the superior
colliculus). This organization presents further complexity to the rules of axon
outgrowth and raises the question of how the topographic information is encoded.
The original experiments of Roger Sperry and later work by many other laboratories
has led to the notion that positional information is found at the level of the
target region. What is this positional information? One possibility is that each
axon has a label that corresponds to an identical label on its appropriate target,
allowing specificity of connections. This seems unpractical; there would need
to be a very large number of labels, and there is no clear targeting mechanism
for the axons. A more likely option was suggested by Sperry in his Chemoaffinity
Hypothesis that suggests that positional information is encoded in the form
of gradients of signaling molecules at the target which would be detected by complementary
gradients of receptors on the axons. This model implies that positional information
can be encoded by a small number of molecules and that this information can be
"read" by axons as they maneuver in the target region. This chemotropic guidance
of axons by diffusable factors that are secreted by cells can involve attractive
or repulsive forces.
Contact the author(s) at: nba_course@uth.tmc.edu
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The University of Texas Health Science Center at Houston
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