Mechanism of Axon Guidance
Following Guidance Cues
Pathways taken by axons during development are highly stereotyped from embryo to embryo. This is because the guidance cues are expressed in specific areas of the embryo, and the axons express specific receptors, allowing for a complex 'map' to be built up in order to guide the axon to its target. Axons follow these cues in a number of ways.
Cues Can be Found on Axons
Using the grasshopper as a model, because its axon pathways had been fully mapped, scientists were able to observe axon growth and guidance throughout development. They noticed that some axons appeared to selectively fasciculate with each other, whilst others changed direction when they came into contact with a different type of axon. This suggested that the axons themselves were signaling to one another.
It has become apparent that axons and their growth cones, differentially express attractants or repellents as well as their complementary receptors. This allows a growing axon to use its neighbours as a signpost in order to reach their target. Once the pioneer axon has grown, follower axons can use it as a scaffold on which to extend.
Pioneer Axons
How can the first axon find its way? Patterning of the early embryo causes differential expression of guidance cues, which create boundaries and compartmentalize the embryo. The pioneer axon is able to sense the different guidance cues, and navigate its way through a seemingly bare environment. For example, in the Grasshopper limb bud, a mix of short range, membrane bound repellents (Sema1); and long-range, diffusible repellents (Sema2) work together to guide the Ti1 axon to its correct target cell cx1. Blocking the function of either of these guidance cues results in abnormal axon growth, as the axon tries to seek its target blind.
Axons can reprogramme
As discussed in the Growth Cone section, commissural axons are repelled by BMP in the roof-plate, and attracted by Netrins in the floor-plate. However, commissural axons in the hind-brain are then able to cross the floor-plate without turning. This is because they have lost their responsiveness to netrin.