10. Axon Guidance

Even after neurons have migrated to form the general structure of the cortical layers, cortical neurons and non-cortical neurons still need to move their rightful places to maximize brain functioning. But as we discussed, the cell bodies don't necessarily move by themselves--they are reliant on their protrusions know as axons. Here is an illustration of a mature pyramidal neuron in the nervous system, whose axon is clearly visible:

In the developing brain, axons do not possess synapses and axon terminals yet. In their place, they have what are called "growth cones," alien hand-shaped structures at the far end of the protrusion that are used for navigation:

The growth cone contains membrane receptors, allowing it to receive and respond to environmental chemical signals. These signals tell the growth cone by telling it whether or not to extend, contract, or break down.

The "fingers" of the alien hand are called filopodia. They consist of actin filaments. The "webbing" between the filopodia is called the lamellipodia, which also contains actin. The "palm" of the growth cone contains microtubules. Actin and microtubules are flexible structures, and are responsible for movement of the growth cone as they allow for cytoskeletal changes.

The principle behind axon guidance is pretty straightforward. Growth cones have chemical signals they like, which are considered chemoattractive, and they have signals they do not like, which are called chemorepulsive signals. Growth cones navigate towards chemoattractive signals, and navigate away from chemorepulsive signals.

How does the growth cone determine whether it likes or dislikes a signal? It depends on how the signal affects the actin and microtubules of the growth cone. Say if we take a growth cone and expose one side of it to cytochalasin, an actin-destablizing agent. The growth cone will not like the destabilization, deeming cytochalasin as a chemorepulsive signal. Hence, it will turn to the opposite direction:

Similar processes take place when the microtubule is disturbed. If we take another growth cone and expose it to nocodazole, a chemorepulsive signal that breaks down microtubules, the growth cone will turn away from the source of exposure and navigate in the opposite direction:

However, if we take yet another growth cone and expose it to a chemoattractive signal, one that it really, really likes, such as the microtubule stablizing agent taxol, t will grow toward the taxol:

Axons also engage in bandwagoning for navigation--sometimes, they will follow what other axons have already done. For example, if many axons are going in the same direction, the newer growth cone will "hang onto" the older axon fascicles (aptly called pioneer axons) and continue its navigation that way. Think of it as watching which door others face in a two-door elevator to determine which door to exit from.

Once the growth cone reaches its target, where the chemoattractant has a really high concentration, it slows down navigation and eventually comes to a stop.