A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope. Neuronal growth cones are situated on the very tips of nerve cells on structures called axons and dendrites. The most crucial roles of the neuronal growth cone are to explore its surroundings ultimately establishing synaptic contacts.
The morphology of the growth cone can be easily described by using the hand as an analogy. The fine extensions of the growth cone are known as "filopodia". The filopodia are like the "fingers" of the growth cone; they contain actin filaments that give them shape and support. In between filopodia--much like the webbing of the hands--are the "lamellipodia". The filopodia contain receptors that are important for axon guidance.
The growth cones are continually being built up through construction of the actin microfilaments and extension of the plasma membrane via vesicle fusion. The actin filaments depolymerize and disassamble on one end to allow free monomers to migrate to the leading edge of the actin filament where it can polymerize and thus reattach. Actin filaments thus do not actually grow but rather migrate. The growth capacity of the axons lies in the microtubules which are located just beyond the actin filaments. Laminins of the basal membrane interact with the integrins of the growth cone to promote the forward movement of the growth cone.
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. 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 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.
- Gordon-Weeks, P. R. 2005. Neuronal Growth Cones, Cambridge University Press, Cambridge. ISBN, 0521 44491 8
- Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 4th ed. pp.1070-1074. McGraw-Hill, New York. ISBN 0-8385-7701-6