Where does axon guidance lead us?

Abstract

During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors. Not only axon guidance molecules but also the regulatory mechanisms that control their spatial and temporal expression are involved in synaptogenesis and synaptic plasticity. Therefore, it is not surprising that genes associated with axon guidance are frequently found in genetic and genomic studies of neurodevelopmental disorders.

Keywords: axon guidance; neural circuit formation; neural networks.

Figure 1.. Growth cones change their responsiveness to the intermediate target upon arrival.

The intermediate target is attractive for axons before contact. However, upon contact with the intermediate target, the growth cone changes its surface receptors. The expression of new receptors allows for the perception of previously undetectable guidance cues associated with the intermediate target. The alterations in surface expression of guidance receptors can be due to changes in transcription, translation, trafficking, or clustering of receptors in the growth cone membrane.