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The Journal of Neuroscience, December 15, 2001, 21(24):9757-9769
Axon Branching Requires Interactions between Dynamic Microtubules
and Actin Filaments
Erik W.
Dent1 and
Katherine
Kalil1, 2
1 Neuroscience Training Program and
2 Department of Anatomy, University of Wisconsin, Madison,
Wisconsin 53706
Cortical neurons innervate many of their targets by collateral axon
branching, which requires local reorganization of the cytoskeleton. We
coinjected cortical neurons with fluorescently labeled tubulin and
phalloidin and used fluorescence time-lapse imaging to analyze
interactions between microtubules and actin filaments (F-actin) in
cortical growth cones and axons undergoing branching. In growth cones
and at axon branch points, splaying of looped or bundled microtubules
is accompanied by focal accumulation of F-actin. Dynamic microtubules
colocalize with F-actin in transition regions of growth cones and at
axon branch points. In contrast, F-actin is excluded from the central
region of the growth cone and the axon shaft, which contains stable
microtubules. Interactions between dynamic microtubules and dynamic
actin filaments involve their coordinated polymerization and
depolymerization. Application of drugs that attenuate either
microtubule or F-actin dynamics also inhibits polymerization of the
other cytoskeletal element. Importantly, inhibition of microtubule or
F-actin dynamics prevents axon branching but not axon elongation.
However, these treatments do cause undirected axon outgrowth. These
results suggest that interactions between dynamic microtubules and
actin filaments are required for axon branching and directed axon outgrowth.
Key words:
microtubule; actin filament; growth cone; collateral axon
branching; cortical development; fluorescence time-lapse imaging
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249757-13$05.00/0
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