The conserved immunoglobulin superfamily member SAX-3/Robo directs multiple aspects of axon guidance in C. elegans.

The C. elegans sax-3 gene encodes a predicted transmembrane protein with five immunoglobulin domains and three fibronectin type III repeats that is closely related to Drosophila Robo. Mutations in sax-3 lead to repeated midline crossing by ventral cord axons that normally do not cross the midline after they join the ventral cord, a phenotype similar to that of robo mutants. sax-3 is also required for guidance of some axons to the ventral cord, implicating this gene in two different types of guidance events. A sax-3::GFP fusion gene is expressed in developing neurons during axon outgrowth, and sax-3 function is required at the time of axon guidance, suggesting that this gene mediates cell interactions during guidance decisions.