Early in the development of vertebrate nervous systems, neurons must connect and differentiate before adopting their specific roles. To ensure this specificity, early neurons lay down an axonal scaffold that provides later axons with a track to follow. In a recent issue of Development, Bak and Fraser report the characteristics that differ between leader — the first axon that emerges, also known as a 'pioneer' axon — and follower axons in the developing zebrafish forebrain.

Using time-lapse fluorescence microscopy, Bak and Fraser were able to detect two distinct classes of behaviours in commissural axons. On approaching the midline, the growth rate of the leader axon slows significantly, whereas the followers maintain a fast growth rate both in and out of the midline region.

This discrepancy in growth rate between leader and follower axons coincided with differences in growth cone morphology. Leader growth cones are more complex, shorter and wider than the elongated growth cones of follower axons. The authors propose that the differences in shape and kinetics are owing to the complex midline environment that leader axons must interpret to ensue that the correct tracks are in place for subsequent follower axons. By using leader axons as guides, follower axons do not need to interpret such signals, and so are simple in shape and have faster growth rates through the midline region.

So, two types of axons engage in the building of the early neuronal scaffold, the leader axon dictating the path that follower axons take. But what happens when the leader axon is eliminated? Bak and Fraser found that, on ablation of the leader axon, the nearest follower axon adopts the role of leader, changing the shape of its growth cone and slowing down as it approaches the midline. This is reminiscent of early observations in the grasshopper, where the elimination of a guidepost cell led to its replacement by a neighbouring cell. So, two key elements in axon guidance — leader axons and guidepost cells — might enjoy some redundancy, perhaps to ensure the success of the guidance process.