[Proteoglycans in the developing brain].

Abstract

The occurrence of multiple proteoglycan species is a characteristic of the brain. To identify each proteoglycan molecule, we have raised several monoclonal antibodies against either the soluble or membrane-bound proteoglycan fraction from 10-day-old rat brains. The monoclonal antibody 1G2 recognized neurocan, a soluble chondroitin sulfate proteoglycan (CSPG) unique to the brain. Immunohistological and cell biological results suggested that neurocan regulates neurite outgrowth through specific binding to N-CAM and Ng-CAM at the surface of neurons. In addition, the expression of neurocan was dependent upon neuronal activity evoked by environmental stimuli at least in the developing barrel field. Another CSPG, 6B4-PG, was expressed specifically in the cerebellar mossy fiber system in the rat hindbrain, suggesting that it plays roles in the establishment of this particular neuronal circuit. A membrane-bound heparan sulfate proteoglycan with a 140 kDa core glycoprotein (tentatively designated growth-can) was shown immunohistologically to be transiently expressed in association with growing axons and at the sites of synapse formation. Thus, many neuronal proteoglycans may be involved in various phases of neuronal network formation in the brain. In the near future, progress both in molecular cloning of core proteins and in glycobiology of carbohydrates of proteoglycans will probably produce much experimental evidence to show that neural proteoglycans play pivotal roles during various stages of brain development.