The semaphorin gene family contains a large number of secreted and transmembrane proteins; some function as repulsive and attractive cues of axon guidance during development. Here, we report cloning and characterization of zebralish transmembrane semaphorin gene, semaphorin 6D (sema6D). Setna6D is expressed predominantly in the nervous system during embryogenesis, as determined by in situ hybridization. We also found that Sema6D binds Plexin-Al in vitro, but not other Plexins. It induces the repulsion of dorsal root ganglion axons, but not sympathetic axons. Consequently, Sema6D might use Plexin-Al as a receptor to repel specific types of axons during development. (C) 2007 Elsevier Inc. All rights reserved.