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The Journal of Neuroscience, November 1, 2002, 22(21):9358-9367
Growth Cone Turning Induced by Direct Local Modification of
Microtubule Dynamics
Kenneth B.
Buck and
James Q.
Zheng
Department of Neuroscience and Cell Biology, University of Medicine
and Dentistry of New Jersey, Robert Wood Johnson Medical School,
Piscataway, New Jersey 08854
Pathfinding by nerve growth cones depends on attractive and
repulsive turning in response to a variety of guidance cues. Here we
present direct evidence to demonstrate an essential and instructive role for microtubules (MTs) in growth cone steering. First, both growth
cone attraction and repulsion induced by diffusible cues in culture can
be completely blocked by low concentrations of drugs that specifically
inhibit dynamic microtubule ends in the growth cone. Second, direct
focal photoactivated release of the microtubule-stabilizing drug taxol
on one side of the growth cone consistently induces attraction (turning
toward the site of application). Using the focal pipette application
method, we also show that local MT stabilization by taxol induces
growth cone attraction, whereas local MT destabilization by the
microtubule-disrupting drug nocodazole induces repulsion (turning
away). Finally, the microtubule-initiated attractive turning requires
the participation of the actin cytoskeleton: local microtubule
stabilization induces preferential protrusion of lamellipodia before
the attractive turning, and the attraction can be abolished by
inhibition of either actin polymerization or the Rho family
GTPases. Together, these results demonstrate a novel steering mechanism
for growth cones in which local and selective modification of dynamic
microtubules can initiate and instruct directional steering. With the
subsequent concerted activity of the actin cytoskeleton, this
microtubule-initiated mechanism provides the growth cone with the
additional means to efficiently navigate through its environment.
Key words:
growth cone; microtubule; cytoskeleton; axon guidance; actin; Rho GTPase
Copyright © 2002 Society for Neuroscience 0270-6474/02/22219358-10$05.00/0
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