Cytoskeleton in Axon Growth

Abstract

Axons and dendrites are the neuronal processes that transmit nerve signals throughout the body. These processes are formed and maintained by the neuronal cytoskeleton, particularly microtubules and actin filaments. Microtubules are the supportive framework of neurites, axons and dendrites, as well as the rails for transporting organelles and cytoplasmic components. Actin filaments support the neuron's outer cortex, and the dynamic protrusion of actin‐filled filopodia and lamellipodia drives neuronal morphogenesis, including axon guidance, branching and regeneration. The initiation of axon formation requires advance of microtubules into filopodial protrusions adherent to the substratum. Polymerisation of microtubule plus ends and dynein‐driven transport of short microtubules provides ‘push’ for continued axonal growth. Actin‐filled protrusions at the axonal terminal, the growth cone, explore the environment for cues that bind receptors and trigger either protrusion and microtubule advance or cessation of protrusion and myosin II contractility that retracts protrusions and limits microtubule advance. Key Concepts The neuronal cytoskeleton generates and supports neuronal shape. Axonal elongation involves accumulation of microtubules through polymerisation, stabilisation and transport. The motile growth cone at the tip of an elongating axon is where the axon is steered to its synaptic target. Dynamic actin filaments drive the growth cone's exploration of its environment. Growth cone adhesive interactions allow traction that advances the growth cone. Neuronal polarisation involves regulation of cytoskeletal dynamics. Extrinsic guidance cues locally regulate actin dynamics and microtubule advance to steer the growth cone. Axonal branching involves cytoskeletal dynamics to produce new streams of microtubule advance. Success in axonal regeneration will require recapitulation of the cytoskeletal dynamics of developing neurons.

An Integrated Cytoskeletal Model of Neurite Outgrowth

“…Here, we briefly summarize their organization and dynamics including assembly, translocation, stabilization, and turnover to develop a foundation for understanding the mechanical process of neurite outgrowth. Several excellent reviews of these processes have been published recently ( Coles and Bradke, 2015 ; Kapitein and Hoogenraad, 2015 ; Cammarata et al, 2016 ; Letourneau, 2016 ; Matamoros and Baas, 2016 ; Voelzmann et al, 2016 ; Omotade et al, 2017 ); therefore, we will not cover them in detail here.…”

“…In combination with F-actin, MTs are essential for axonal elongation and growth cone guidance ( Coles and Bradke, 2015 ; Kapitein and Hoogenraad, 2015 ; Letourneau, 2016 ). Like actin filaments, MTs are polarized structures with polymerization occurring at their plus ends by the addition of tubulin dimers.…”

Modeling the Axon as an Active Partner with the Growth Cone in Axonal Elongation

“…We emphasize that here we choose to focus on actin and myosin in the cortex because they are critical in the process of axonal elongation and guidance (56). In addition, from a biophysical standpoint, actin and myosin generate the majority of contractile forces in neurons.…”