Coiling of microtubule bundles in a retracted axon. Image courtesy of Peter Baas, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

Axonal elongation requires the polymerization of tubulin to form microtubules. Axonal retraction is just as important as elongation in the wiring of the nervous system, but its underlying mechanisms remain obscure. A commonly held belief is that retraction involves a global depolymerization of microtubules, although the experimental evidence is not uniform in this regard. Now He et al. have taken a closer look at axonal retraction in culture, and have found that, instead of depolymerizing, microtubules form coiling and sinusoidal bundles as the axon shortens.

The authors used chick sensory neurons and exposed them to nitric oxide donors to elicit retraction. Morphologically, this type of axonal retraction closely resembles what is seen in vivo: an enlarged distal region, a thin remnant and sinusoidal bends along the axon are observed. He et al. used quantitative immunofluorescence methods to determine whether there was a significant decrease in the amount of microtubule polymer during this form of retraction, and found that there was no difference between control axons and those exposed to the nitric oxide donor. Instead, they found that the microtubules formed coils that seemed to follow the contours of the sinusoidal bends of the shortening axon. Furthermore, they compared this observation with the retraction that is seen in response to the microtubule-depolymerizing agent nocodazole. Morphologically, nocodazole-treated axons differed from those treated with nitric oxide: the axonal shaft withered, and abnormal 'beads' and lateral extensions formed along its length. But more importantly, microtubules were not detected, indicating that the wholesale depolymerization of tubulin is accompanied by a totally different axonal response. Last, He et al. tested whether axons treated with the microtubule-stabilizing agent taxol would retract in response to nitric oxide. Indeed, the axons retracted, and they showed the same coiling and sinusoidal bundles that the authors had described previously.

He et al. propose that the coiling of microtubules depends on alterations in the activity of axonal motor proteins, the identities of which remain to be established. In more general terms, it is interesting to compare retraction with elongation in the light of this study. Like axonal retraction, elongation was first proposed to depend strictly on tubulin polymerization, but subsequent studies showed that tubulin polymers can be transported, 'ready made', down the axon by molecular motors. It would not be surprising if, similarly, retraction involves both depolymerization and the reconfiguration of microtubules to achieve the precise wiring of the developing brain.