A RAT G-PROTEIN-COUPLED RECEPTOR SELECTIVELY EXPRESSED IN MYELIN-FORMING CELLS

By screening an olfactory bulb cDNA library using dopamine receptor pr obes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. I n situ hybridization analysis showed that Edg-2 mRNA expression is res tricted to myelinated structures, e.g. corpus callosum or peripheral n erves. A weaker expression in various peripheral organs was also detec ted in newborns. A 3.8-kb transcript was found at high levels in highl y myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrenc e in Schwann cells in the peripheral nervous system. One hundred perce nt of Edg-2 mRNA-containing cells in the brain also expressed mRNA enc oding myelin-basic-protein, a marker of oligodendrocytes. This restric ted olygodendrocytes localization was confirmed by the absence of cell ular colocalization of Edg-2 and glial fibrillary acidic protein, an a strocytic marker. During prenatal development, Edg-2 mRNA expression w as high in the cortical neuroepithelium and meningeal layer at E16, ex tended later to other neuroepithelia, and disappeared shortly after bi rth. During brain postnatal development, Edg-2 mRNA expression in myel inated structures followed a caudo-rostral gradient, similar to that o f myelination. Thus, Edg-2 is the first G protein-coupled receptor fou nd to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual r ole (i) in neurogenesis, during embryonic development, and (ii) in mye lination and myelin maintenance, during postnatal life.