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Axon guidance

Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which axons extend to reach their correct targets. Axons often follow very precise paths in the nervous system, it is important in neural development, and how they manage to find their way so accurately is being researched. Axons are guided along specific pathways by attractive and repulsive cues in the extracellular environment. At the growing tip of axons, a highly motile structure, called growth cone, it "sniffs out" the extracellular environment for signals that instruct the axon which direction 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. A combination of genetic and biochemical methods has led to the discovery of several important classes of axon guidance molecules and their receptors,including Ephrins, Netrins, Semaphorins and Slits. Netrins: Netrins are secreted molecules that can act to attract or repel axons by binding to their receptors, DCC and UNC5; Slits, semaphorins, and ephrins act primarily as repellents but can be attractive or adhesive in some contexts. In addition, many other guidance factors have been identified: neurotrophins, TGF-beta family members, BMPs, hepatocyte growth factor (HGF) factor, and additional candidate receptors include the protocadherin family, immunoglobulin family cell adhesion molecules (Ig-CAMs), neurexins, and odorant receptors. Guidance cues steer axons by regulating cytoskeletal dynamics in the growth cone through signaling pathways that are still not well understood. 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.

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