Neurite elongation on chondroitin sulfate proteoglycans is characterized by axonal fasciculation

In the developing or regenerating nervous system, migrating growth cones are exposed to regulatory molecules that positively and/or negatively affect guidance. Chondroitin sulfate proteoglycans (CSPGs) are complex macromolecules that are typically negative regulators of growth cone migration in vivo and in vitro. However, in certain cases, neurites sometimes traverse regions expressing relatively high levels of CSPGs, seemingly a paradox. In our continuing efforts to characterize CSPG inhibition in vitro, we manipulated the ratio of CSPGs to growth-promoting laminin-1 to produce a substratum that supports outgrowth of a subpopulation of dorsal root ganglia (DRG) neurites, while still being inhibitory to other populations of DRG neurons [Exp. Neurol. 109 (1990), 111; J. Neurobiol. 51 (2002), 285]. This model comprises a useful tool in the analysis of mechanisms of growth cone guidance and is particularly useful to analyze how CSPGs can be inhibitory under some conditions, and growth permissive under others. We grew embryonic (E9-10) chicken DRG neurons on nervous system-isolated, substratum-bound CSPGs at a concentration that supports an intermittent pattern of outgrowth, alternating with regions adsorbed with growth-promoting laminin-1 alone, and analyzed outgrowth behaviors qualitatively and quantitatively. A novel finding of the study was that DRG neurites that elongated onto CSPGs were predominantly fasciculated, but immediately returned to a defasciculated state upon contact with laminin-1. Further, cursory inspection suggests that outgrowth onto CSPGs may be initially accomplished by pioneer axons, along which subsequent axons migrate. The outgrowth patterns characterized in vitro may accurately reflect outgrowth in vivo in locations where inhibitory CSPGs and growth-promoting molecules are coexpressed, e.g., in the developing retina where fasciculated outgrowth may be instrumental in the guidance of retinal ganglion cells from the periphery to the optic fissure.