Brain derived versican V2 is a potent inhibitor of axonal growth

In this paper, we identify the chondroitin sulfate proteoglycan versican V2 as a major inhibitor of axonal growth in the extracellular matrix of the m ature central nervous system. In immunohistochemical and in situ hybridizat ion experiments we show that this tissue-specific splice variant of versica n is predominantly present in myelinated fiber tracts of the brain and in t he optic nerve, most likely being expressed by oligodendrocytes. We demonst rate that isolated versican V2 strongly inhibits neurite outgrowth of centr al and peripheral neurons in stripe-choice assays using laminin-1 as permis sive substrate. The inhibitory character of versican V2 is maintained after removal of chondroitin sulfate and N- and O-linked oligosaccharide side ch ains, but it is abolished after core protein digestion with proteinase-K. O ur data support the notion, that intact versican V2 prevents excessive axon al growth during late phases of development and hereby participates in the structural stabilization of the mature central nervous system.