Mechanisms regulating interpretation of guidance cues during development, maturation, and following injury

Guidance molecules are not inherently attractive or repulsive, but rather, are interpreted as such based on the context in which they are encountered. Thus, accurate wiring of the central nervous system is inextricably tied to the internal state of neurons and their local environment. To protect functional integrity, these carefully formed circuits are stabilized via a combination of neuronal and environmental changes during maturation and following injury. While necessary, such modifications create obstacles for reconstruction of damaged circuits. Here, we consider the effects of maturation and injury induced changes on the interpretation of guidance cues by regenerating neurons and the problems they pose for faithful reconstruction of functional circuits.