Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately remains a major puzzle.

Mechanisms

Growing axons have a highly motile structure at the growing tip called the growth cone, which "sniffs out" the extracellular environment for signals that instruct the axon which way to grow. These signals, called guidance cues, can be fixed in place or diffusible; they can attract or repel axons. Growth cones contain receptors that recognize these guidance cues and interpret the signal into a chemotropic response. The general theoretical framework is that when a growth cone "senses" a guidance cue, the receptors activate various signaling molecules in the growth cone that eventually affect the cytoskeleton. If the growth cone senses a gradient of guidance cue, the intracellular signaling in the growth cone happens asymmetrically, so that cytoskeletal changes happen asymmetrically and the growth cone turns toward or away from the guidance cue.

Studying axon guidance

Scientists use various methods to work out how axons find their way. In genetic model organisms like mice, nematodes, and fruit flies, scientists can generate mutations and see whether and how they cause axons to make errors in navigation. In vitro experiments can be useful for direct manipulation of growing axons. A popular method is to grow neurons in culture and expose growth cones to purified guidance cues to see whether these cause the growing axons to turn. These experiments are often done using cells from the frog Xenopus laevis because Xenopus embryos are easy to obtain and Xenopus cells are relatively hardy and grow well at room temperature.

Axon guidance model systems

Several axon "paths" have been extensively studied and are used as model systems to further understand the mechanisms of axon guidance. These include:

• the retinotectal projection in Xenopus laevis and zebrafish
• commissural axons in the developing spinal cord, which are first repelled away from the roof plate and then attracted toward the floor plate
• the peripheral nervous system, in particular, the Ti1 pathway in the grasshopper limbs are used to study axon guidance and neurite outgrowth in the peripheral nervous system. The Ti1 growth cones are attracted to beads coated with semaphorin as well as cells expressing semaphorin on the cell surface.neuroscience