Neurite Outgrowth in Response to Patterns of Chondroitin Sulfate Proteoglycan: Inhibition and Adaptation

Proteoglycans are a structurally diverse class of molecules that interact with many ECM and cell surface components, thereby contributing significantly to a multitude of processes. One function for these macromolecules is the regulation of neurite outgrowth. Proteoglycans are present in axon-free regions of the developing nervous system, where the temporal pattern of their expression suggests a possible role as barrier molecules. In other regions, they are expressed where axons grow and may exist at these sites in combination with growth-promoting molecules, such that their influence is not inhibitory, but rather modulatory. In vitro, when presented in high concentrations in combination with laminin, chondroitin sulfate proteoglycan (CSPG) is inhibitory to growth cone advance for each of three neuronal types tested. Enzymatic degradation of the carbohydrate portion of this molecule (glycosaminoglycan) indicates that it is responsible for the inhibition. However, growth cones can grow on CSPG (bound to laminin) when presented in a stepwise, graded distribution, with the response to the CSPG step gradient being different for each of three neuronal populations. Although the behavior of each cell type is unique, a common behavior of each cell type on the CSPG step gradient is a decrease in the rate of neurite outgrowth with increasing CSPG concentration. These data suggest that different patterns of neurite outgrowth may result from the regulation of the ratio of growth-promoting to growth-inhibiting molecules in the growth cones immediate environment.