Cloning and characterization of SDF-1 gamma a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system

The cytokines SDF-1 alpha and -1 beta are two alternatively spliced variant s of the CXC (alpha) chemokines that are highly conserved among species. SD F-1 alpha was shown to function as a B-cell maturation factor, a ligand for the CXCR4 (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell-tropic HIV-1 strains and inducing cell death in human neuronal c ell lines. In this report the cloning of the rat SDF-1 beta cDNA and a new SDF-1 isoform, SDF-1 gamma, are presented. Using Northern blot analysis, th e expression pattern of both isoforms was studied in different tissues and it is shown that during postnatal development of the central and peripheral nervous system SDF-1 beta- and SDF-1 gamma-mRNA expression is inversely re gulated. Whilst SDF-1 beta-mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF-1 gamma-mRNA is expressed at higher leve ls in adulthood. After peripheral nerve lesion a transient increase in SDF- 1 beta-mRNA expression is observed. As revealed by in situ hybridization, n eurons and Schwann cells are the main cellular sources of both SDF-1 beta a nd SDF-1 gamma mRNAs in the nervous system. Computer-assisted analysis reve aled that both transcripts encode secreted peptides with putative proteolyt ic cleavage sites which might generate novel neuropeptides.