Witte et al. show that the choice requires an overlooked ingredient: stable microtubules.
As a neuron matures, it sprouts several projections, or neurites. One neurite continues to lengthen and becomes an axon, while the others become dendrites. Although researchers have probed how actin promotes this process, they don't understand microtubules' role.
Witte et al. gauged microtubule dynamics in cultured hippocampal neurons. They found that microtubules in the axon were more stable than those in other neurites. If the researchers added the microtubule-stabilizing drug taxol to cells that were just extending neurites, multiple axons resulted.
The team then exposed cells at the neurite-sprouting stage to a light-activated form of taxol. When they shone UV light on one of the neurites, it would usually become the axon. By dosing taxol-treated cells with a marker for growing microtubules, the scientists also found that taxol shifted the polymerizing microtubules from the neurite shaft to the tip.
The results suggest that microtubule stabilization helps dictate which neurite will specialize into an axon. The team hypothesizes that stabilizing the fibers within the axon directs microtubule extension toward the tip, thus pushing the end of the projection forward.