Axon Branching Requires Interactions between Dynamic Microtubules and Actin Filaments

These results suggest that interactions between dynamic microtubules and actin filaments are required for axon branching and directed axon outgrowth

Erik W. Dent; Katherine Kalil


Scholarcy highlights

  • Cortical neurons innervate many of their targets by collateral axon branching, which requires local reorganization of the cytoskeleton
  • In smaller growth cones, which we have identified previously as rapidly growing, the central region is occupied by straight bundles of microtubules as well as actin filaments
  • Microtubules and F-actin appear to be closely apposed. We confirmed this with electron microscopy of fixed cortical growth cones, which showed that microtubules splaying from the central loop extend into the lamellipodium, where they are closely apposed to bundles of actin filaments. These results show that development of branches from a large paused growth cone or from its remnants along the axon shaft is accompanied by local accumulation of F-actin, which coincides with splaying and fragmentation of bundled microtubules
  • We found that branching from the growth cone and the axon shaft is always preceded by splaying apart of looped or bundled microtubules which is accompanied by localized accumulation of F-actin
  • Dynamic microtubules colocalize with F-actin in transition regions of growth cones and axon branch points, consistent with observations in fixed growth cones, whereas F-actin is excluded from regions of stable microtubules
  • Drugs that attenuate either microtubule or actin dynamics concomitantly abolish microtubule–F-actin interactions at the growth cone and at axon branch points. These drug treatments inhibit axon branching but not axon elongation, demonstrating that interactions between dynamic microtubules and actin filaments are essential for initiating axon growth in new directions
  • Microtubules may be directed toward regions of attenuated F-actin flow associated with growth cone–target interactions, or dynamic microtubule ends may be captured by actin filaments during growth cone turning

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