Growth Cone - Axon Guidance

Axon Guidance

Movement of the axons is controlled by an integration of its sensory and motor function (described above) which is established through second messengers such as calcium and cyclic nucleotides. The sensory function of axons is dependent on cues from the extracellular matrix which can be either attractive or repulsive, thus helping to guide the axon away from certain paths and attracting them to their proper target destinations. Attractive cues inhibit retrograde flow of the actin filaments and promote their assembly whereas repulsive cues have the exact opposite effect. Actin stabilizing proteins are also involved and are essential for continued protrusion of filopodia and lamellipodia in the presence of attractive cues, while actin destabilizing proteins are involved in the presence of a repulsive cue.

A similar process is involved with microtubules. In the presence of an attractive cue on one side of the growth cone, specific microtubules are targeted on that side by microtubule stabilizing proteins, resulting in growth cone turning in the direction of the positive stimulus. With repulsive cues, the opposite is true: microtubule stabilization is favored on the opposite side of the growth cone as the negative stimulus resulting in the growth cone turning away from the repellent. This process coupled with actin-associated processes result in the overall directed growth of an axon.

Growth cone receptors detect the presence of axon guidance molecules such as Netrin, Slit, Ephrins, and Semaphorins. It has more recently been shown that cell fate determinants such as Wnt or Shh can also act as guidance cues. Quite interestingly, the same guidance cue can act as an attractant or a repellent, depending on context. A prime example of this is Netrin-1, which signals attraction through the DCC receptor and repulsion through the Unc-5 receptor. Furthermore, it has been discovered that these same molecules are involved in guiding vessel growth. Axon guidance directs the initial wiring of the nervous system and is also important in axonal regeneration following an injury.