Molecular mechanisms of axonal growth

Outgrowth of axons during neuronal development, as well as their regeneration after injury, of the adult nervous system is controlled by specific extracellular cues which are diffusible, or bound to cell membranes or extracellular matrix. The exact molecular mechanisms through which these extracellular signals are integrated by the growing axon, are not yet well defined. However, it is widely accepted that most, if not all, signaling cascades triggered by guidance cues eventually converge onto the cytoskeleton. The action of extracellular guidance factors is thus modulated not only by specific membrane receptors, but also by cytoskeletal and cytoskeleton-associated molecules within the axon. In fact, the cytoskeleton represents a point of convergence and integration of both neuron-intrinsic and extrinsic factors. Moreover, in recent years, there has been increasing evidence for the involvement of a coordinated cross-talk between actin filaments and microtubules, the two main components of the growth cone cytoskeleton. Their reorganization is complex and involves numerous cytoskeleton-associated proteins whose function is regulated via activation or inhibition of particular signaling pathways.