The emerging role of forces in axonal elongation

An understanding of how axons elongate is needed to develop rational strategies to treat neurological diseases and nerve injury. Growth cone-mediated neuronal elongation is currently viewed as occurring through cytoskeletal dynamics involving the polymerization of actin and tubulin subunits at the tip of the axon. However, recent work suggests that axons and growth cones also generate forces (through cytoskeletal dynamics, kinesin, dynein, and myosin), forces induce axonal elongation, and axons lengthen by stretching. This review highlights results from various model systems (Drosophila, Aplysia, Xenopus, chicken, mouse, rat, and PC12 cells), supporting a role for forces, bulk microtubule movements, and intercalated mass addition in the process of axonal elongation. We think that a satisfying answer to the question, “How do axons grow?” will come by integrating the best aspects of biophysics, genetics, and cell biology.

► A common model proposes axons elongate through mass addition at the growth cone.
► A new model suggests elongation occurs because growth cones generate forces.
► Forces are generated through the interaction of cytoskeletal dynamics and motors.
► Forces cause advance of the growth cone and axonal stretching.
► ‘Growth’ happens by the addition of new material along the axon.