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Expose growth cone
to a graded concentration
of cytochalasin to depolymerize
actin on one side.
axon turns
FIGURE 5.15 Image of a growth cone showing actin in green
and Ena/Vasp in red located at the tips of the filopodia where these
proteins act as anticapping agents, preventing the binding of actin
capping proteins and thus encouraging plus end elongation. (From
Lanier and Gertler, 2000)
Stabilize microtubules
on one side with taxol
axon turns
Growth cones have the ability to sense their envi-
ronment and make choices based on extracellular
information. These choices are made as the growth
cone passes through a complex environment of chem-
ical factors and physical terrain. On a dried cracked
collagen surface, growing axons often follow the
pattern of the stress fractures (Figure 5.16A). When
tracts or commissures are wounded or experimentally
severed, axons may be physically impeded from
growing as they normally would. In such cases, it is
sometimes possible to provide axons with an artificial
mechanical pathway across the wound (Silver and
Ogawa, 1983) (Figure 5.16B). Mechanical support is
necessary and influential, but axon growth and guid-
ance are based on molecular mechanisms. To discover
these mechanisms, factors are often tested in tissue
culture to see whether they influence the rate and
direction of axonal growth. Many molecules have been
identified in this way, and such studies show that a
single type of growth cone can respond to a variety of
different cues. For example, embryonic spinal neurons
from frog embryos respond to at least a dozen differ-
ent factors tested, and this implies that growth cones
are highly attuned sensory beasts with rich arrays of
receptor molecules to sample various aspects of their
environment. Genetic approaches in Drosophila and
nematodes have led to the identification of many genes
for guidance cues and their receptors, which when
disrupted lead to growth and pathfinding errors.
When neurons are plated on plain glass or tissue
culture plastic, the cells often attach but rarely put out
long neurites with active growth cones. However,
Destabilize microtublues
on one side with nocodazole
axon turns
FIGURE 5.14 Actin and microtubules steer growth cones. A.
Local depolymerization of actin on one side of a growth cone causes
it to turn the other way. B. Local stabilization of microtubules on one
side of a growth cone causes it to turn toward that side. C. Destabi-
lization of microtubules on one side causes it to turn the other way.
(After Buck and Zheng, 2002; Yuan et al., 2003)
(Lanier and Gertler, 2000; Lebrand et al., 2004) (Figure
5.15). All these actin and microtubule-associated pro-
teins and many others have to be regulated properly as
the growth cone navigates, and there are a large and
growing number of identified kinases and phos-
phatases that add and remove phosphate groups from
these proteins, thus activating and inactivating them.
These enzymes are in turn regulated by receptors on
the growth cone surface that sense the substrates and
guidance molecules that the growth cone encounters in
its journey.
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