TRANSCRIPTS FOR SECRETED AND GPI-ANCHORED BREVICAN ARE DIFFERENTIALLYDISTRIBUTED IN RAT-BRAIN

Brevican is a member of the aggrecan/versican family of proteoglycans. in contrast to the other family members, brevican occurs both as solu ble isoforms secreted into the extracellular space and membrane-bound isoforms which are anchored to the cell surface via a glycosylphosphat idylinositol (GPI) moiety. Expression of both variants, which are enco ded by two differentially processed transcripts from the same gene, is confined to the nervous system. In the current study, we have used in situ hybridization to examine the cellular sites of synthesis for bot h mRNAs during postnatal development of the rat brain. Whereas the 3.6 -kb transcript encoding secreted brevican displays a widespread distri bution in grey matter structures, including cerebellar and cerebral co rtex, hippocampus and thalamic nuclei with silver grains accumulating over neuronal cell bodies, the smaller transcript (3.3 kb) encoding GP I-anchored isoforms appears to be largely confined to white matter tra cts and diffusely distributed glial cells. This expression pattern is further confirmed by reverse transcriptase-polymerase chain reaction ( RT-PCR) experiments with RNA from different glial cell cultures, and b y biochemical data demonstrating that the crude membrane fraction from isolated optic nerve contains high amounts of phosphatidylinositol-sp ecific phospholipase C (PI-PLC)-sensitive brevican immunoreactivity. D uring ontogenetic development, both brevican transcripts are generally up-regulated. However, the expression of glypiated brevican is delaye d by about 1 week, compared with the expression of the secreted isofor m. This late appearance of GPI-linked brevican, its predominant expres sion in glial cells and its tight association with brain myelin fracti ons suggest a functional role in neuroglia.