The secreted Slit repellents and their Roundabout (Robo) receptors were originally identified as important axon guidance molecules. The SLIT-ROBO interaction has been found to be involved in the regulation of cell migration, cell death and angiogenesis and, as such, has a pivotal role during the development of other tissues such as the lung, kidney, liver and breast []. There are four Robo homologues in vertebrates (Robo1-4).Robo3 is a divergent member of the family that does not bind Slit proteins []. Robo3 exists in two splice isoforms with different intracellular domains: Robo3.1 is expressed on precrossing commissural axons and allows midline crossing (partly by inhibiting Slit signaling through Robo1/2), whereas Robo3.2 is expressed postcrossing and prevents midline recrossing []. NELL2 (neural epidermal growth factor-like-like 2) has been identified as a Robo3 ligand that repels commissural axons and helps steer them to the midline [].
