Divergent properties of mouse netrins

The netrins are a small but highly conserved family of axonal guidance signals found throughout the animal kingdom. This sequence conservation was used to isolated cDNAs for two mouse netrins. Analysis of their expression patterns and functional properties showed that mouse netrin-1 is in most respects similar to its orthologs in other vertebrates while the properties of netrin-3 differ markedly from those of other members of this protein family. In contrast to netrin-1 which is widely expressed both in the developing nervous system and in mesodermal tissues, netrin-3 transcripts are largely restricted to dorsal root ganglia and the developing limb buds. Netrin-3 binds with a significantly lower affinity to the netrin receptor DCC (deleted in colorectal cancer) and is also ineffective in eliciting the outgrowth of commissural axons in vitro. These results demonstrate that, although the netrins are highly conserved signals that guide axons to or away from the midline of the developing nervous system, at the same time they show a surprising degree of divergence in vertebrates.