Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family

The semaphorins comprise a large family of membrane-bound and secreted prot eins, some of which have been shown to function in axon guidance. We have c loned a transmembrane semaphorin, Sema W, that belongs to the class IV subg roup of the semaphorin family. The mouse and rat forms of Sema W show 97% a mino acid sequence identity with each other, and each shows about 91% ident ity with the human form. The gene for Sema W is divided into 15 exons, up t o 4 of which are absent in the human cDNAs that we sequenced. Unlike many o ther semaphorins, Sema W is expressed at low levels in the developing embry o but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indi cating that vertebrate transmembrane semaphorins, like secreted semaphorins , can collapse growth cones. Genetic mapping of human SEMAW with human/hams ter radiation hybrids localized the gene to chromosome 2p13. Genetic mappin g of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This loca lization places Semaw within the locus for motor neuron degeneration 2, mak ing it an attractive candidate gene for this disease.