Cloning and characterization of SDF-1γ 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 variants of the CXC (alpha) chemokines that are highly conserved among species. SDF-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 cell 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, the 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 regulated. Whilst SDF-1 beta-mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF-1 gamma-mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a transient increase in SDF-1 beta-mRNA expression is observed. As revealed by in situ hybridization, neurons and Schwann cells are the main cellular sources of both SDF-1 beta and SDF-1 gamma mRNAs in the nervous system. Computer-assisted analysis revealed that both transcripts encode secreted peptides with putative proteolytic cleavage sites which might generate novel neuropeptides.