Cytoskeleton in Axon Growth

Abstract

During development, neurons extend two different types of processes, typically several short dendrites and one long axon. The axon forms synapses with dendrites of other neurons to integrate into a neuronal network. Axons can extend to enormous lengths. Their growth is guided and exactly controlled to guarantee the correct neuronal connections. Microtubules and actin filaments, the two major cytoskeletal elements, are the key players in these processes. They form the backbone for axon extension, provide the construction material for axon elongation, and are the site of convergence of extracellular and intrinsic signals. Correct path finding of the axon is ensured by a specialized and highly dynamic structure at the tip of the growing axon, the growth cone. Its dynamic cytoskeleton is the machinery that establishes, controls and directs axon growth. Overall, the cytoskeleton determines the distinction of axons and dendrites and aberrant changes in the cytoskeleton are a major cause of regenerative failure after spinal cord injury. Key concepts: The growth cone is the highly motile tip of a growing axon, where the axon becomes elongated. Growth cone motility is regulated by cytoskeletal dynamics. Actin filaments determine growth cone shape and are involved in path finding. Microtubules give structure to the axon shaft and are essential for axon elongation. Guidance cues act on the cytoskeleton in the growth cone. A dynamic interaction between actin filaments and microtubules is necessary to steer axon growth. The cytoskeleton regulates neuronal polarity. Injury induced pathological changes of the cytoskeleton are a major cause for lack of regeneration after spinal cord injury.

Continuum mechanical modeling of axonal growth

“…The main structural scaffold of the neuron, the cytoskeleton (Fletcher and Mullins, 2010), is an evolving dynamic polymeric structure that is actively involved in axonal outgrowth (Stiess and Bradke, 2009). The cytoskeleton is composed of three main types of filamentous polymers: F-actin, microtubules and neurofilaments.…”

“…While microtubules are the stiffest cytoskeleton components (Conde and Cáceres, 2009) and F-actin are less rigid on their own, the latter are able to build organized stiff structures thanks to the presence of high concentrations of crosslinkers (Fletcher and Mullins, 2010). Their complex interactions as well as their relations with the surrounding structures and associated motor proteins (e.g., Dynein or Kinesin for microtubules or Myosin II for F-actin) are crucial for proper axonal development (Stiess and Bradke, 2009). They also are heterogeneously distributed along the axon domain (Mitchinson and Kirschner, 1988;Edward, 2009).…”