Axonal Guidance: Making Connections

The vertebrate brain contains millions of neuronal and glial cells arranged in a highly organized manner forming functional neural circuits. To form these circuits during brain development, neurons extend an axon from the cell body to make connections with neurons in target brain areas, which can be a considerable distance away from the neuronal cell body. To ensure that axons accurately elongate toward the correct target field over such a distance, specific guidance cues are used to navigate the axons through their environment in a reproducible pattern of growth. These cues involve guidance molecules that can elicit attractive or repellent guidance on the extending axon and can act over long distances by secretion into extracellular space or over short distances through direct cell contact. In response to the guidance cues, the distal tip of the axon, known as the growth cone, undergoes dynamic structural changes to ensure that it is continually growing in the correct direction. In this chapter, we will discuss the range of highly conserved mechanisms and molecules involved in axon guidance, the biological changes that occur in axons during guidance, and the major assays used to measure the guidance of neuronal axons in vitro.