Principal mechanisms of axonal growth
Axonal growth is a key mechanisms of neural circuit formation. A) In the developing brain, neuronal axons (and dendrites) grow out along reproducible paths (curved arrows) via growth cones at their tips. B) Through guided growth of axons, neurons form synapses (black arrow heads) with their appropriate partner cells. In correctly hard-wired neuronal circuits involving sensory neurons (red), interneurons (beige) and motorneurons (blue), action potentials (yellow zigzag arrows) travel along axons and trigger transmission at synapses (black arrow heads). These highly regulated events of information transfer and processing constitute behaviour.

How do growth cones advance and navigate?

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The cytoskeleton constitutes the key machinery of growth cones. Veil-like lamellipodia contain mesh-like networks of actin filaments (randomly oriented red lines), whereas pointed filopodia contain bundled actin filaments (parallel red lines); microtubules (green) are bundled in the axon, but single splayed microtubules extend into the periphery of the growth cone, often reaching into filopodia.

What is the specific contribution of actin and microtubules?

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Microtubules primarily mediate axonal extension, actin networks its directionality. A) Single splayed microtubules (MTs) push from the axon into the actin-rich periphery of growth cones, essentially powered by polymerisation processes at MT plus ends. Upon stabilisation, such MTs guide bulk elongation of axonal MTs, thus elongating the axon. External guidance cues (orange arrow) influence the directionality of these events. Pharmacological F-actin depletion (B) or genetic impairment of F-actin networks (C; enabled mutant) does not inhibit the principal ability of axons to elongate in culture, illustrating that MTs represent the key machinery of axon elongation. However, elongating axons fail to respond to extracellular signals in the absence of F-actin (B,C), illustrating that F-actin is an essential mediator of signal-induced growth regulation reflected in the directionality of growth cones.

How are the dynamics of actin and microtubules regulated during axon growth? (>>>)