Proteoglycans as modulators of axon guidance cue function

Organizing a functional neuronal network requires the precise wiring of neuronal connections. In order to find their correct targets, growth cones navigate through the extracellular matrix guided by secreted and membrane-bound molecules of the slit, netrin, ephrin and semaphorin families. Although many of these axon guidance molecules are able to bind to heparan sulfate proteoglycans, the role of proteoglycans in regulating axon guidance cue function is only now beginning to be understood. Recent developmental studies in a wide range of model organisms have revealed a crucial role for heparan sulfate proteoglycans as modulators of key signaling pathways in axon guidance. In addition, emerging evidence indicates an essential role for chondroitin sulfate proteoglycans in modifying the guidance function of semaphorins. It is becoming increasingly clear that extracellular matrix molecules, rather than just constituting a structural scaffold, can critically influence axon guidance cue function in development, and may continue to do so in the injured adult nervous system.