AXON EXTENSION AND THE NEURONAL CYTOSKELETON
(a brief introduction)

The establishment of connections between neurons and their targets is of fundamental importance to the genesis of a functional nervous system. In order to connect with targets long distances away, neurons extend processes called axons (Fig. 1; forebrain neurons, green arrows show axons labeled green with an antibody to tubulin. Blue arrows denote cell bodies of the two neurons in the field of view). Axon extension occurs at the tip of the axon, the growth cone (Fig. 2). Growth cones have a variety of shapes and forms. It is important to note that growth cones are highly dynamic structures that can dramatically change form on a timescale of minutes. Axon extension is a three step process (Fig. 3). The first step in axon extension is termed protrusion and involves the extension of the growth cone membrane in the form of filopodia and lamellipodia. The next step is termed engorgement and is characterized by the movement of cytoplasmic elements into the protruded region of the growth cone. Finally, consolidation occurs which involves the loss of protrusive activity from the region of the growth cone that has been engorged. By repeating this three step process the axon advances and grows in length.

The neuronal cytoskeleton consists of three main components: actin filaments, microtubule and neurofilaments (Figure 4, red=actin, green=microtubules). Investigating the dynamics and organization of the cytoskeleton is of fundamental importance to understanding the mechanism of axon extension and retraction. Actin filaments are required for the protrusion phase of axon extension. Actin filament polymerization drives the forward extension of filopodia and lamellipodia. Microtubule   polymerization and transport of organelles mediate the engorgement process. Inhibition of either actin or microtubule polymerization hinders the ability of axons to extend. In the complete absence of microtubules axons do not extend at all. Thus, both actin filaments and microtubules are necessary for axon extension. The role of neurofilaments in axon extension is not yet clear.

A goal of modern developmental neuroscience and cell biology is to understand how axons are extended and how axon extension is regulated by extracellular signals. Intracellular proteins have been identified that regulate axon extension and growth cone guidance. These proteins fall into two major classes: proteins that directly alter the dynamics/organization of the cytoskeleton, and proteins that alter the activity of these proteins. The function of these cytoskeleton regulatory proteins is in turn regulated by extracellular signals that direct axons to extend or retract

For an excellent review on the role of the cytoskeleton in axon extension and guidance see the article by Dent and Gertler

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