As we previously mentioned, the process of axon guidance in both vertebrates and invertebrates has been conserved and occurs in a highly ordered and stereotyped manner (reviewed in Araujo and Tear, 2003). Studies in the past two decades have provided compelling evidence for cellular interactions between growth cones and their environment in directing axon pathfinding and have led to the identification of different families of guidance cues. Four types of basic mechanisms are thought to steer axon growth: contact attraction, chemoattraction, contact repulsion, and chemorepulsion (Figure 3; reviewed in Tessier-Lavigne and Goodman, 1996). However, these designations are dependent on the environmental context in which axon pathfinding is taking place, as some families of guidance cues have both diffusible and nondiffusible members and some individual cues themselves can act as attractants for some axons and repellents for others. Thus, axon pathfinding is directed by the coordinate action of multiple attractant and repellent cues integrated by the growth cone along the pathway. In this section, we will describe the characteristics of a guidance cue and the techniques widely used to test for guidance activity. We will then describe the main families of guidance cues identified to date.
How are we able to identify molecules that regulate the process of axon pathfinding? A candidate protein has to fulfill several criteria to be classed as a guidance cue: (1) it has to be expressed at the right
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