By screening of E17.5 mouse brain cDNA libraries, we isolated two cDNAs encoding new plexin-like proteins. Sequencing revealed that these two proteins were type 1 membrane proteins which showed over 60% identity at the amino acid level to mouse plexin 1. Moreover, putative extracellular segments of these two proteins had three repeats of a cysteine-rich domain which is a common motif for plexin proteins. Thus, we named these two proteins mouse plexin 2 and mouse plexin 3. We obtained mouse plexin 3 cDNA clones in which a part of protein-coding region was deleted. Also, Northern blot analysis showed molecular heterogeneity in mouse plexin 2 mRNAs. These findings indicate that, in the mouse, plexins comprise a molecular family (the plexin family). (C) 1996 Academic Press, Inc.