Based on studies in mice, ROBO3 isoforms ROBO3.1 and ROBO3.2 bind to a secreted ligand NELL2 (neural epidermal growth factor-like-like 2). This interaction involves the EGF-like domains of NELL2 and the FN3 (FNIII) domain of ROBO3. Pre-crossing commissural axons which express ROBO3.1 are repelled by NELL2. Post-crossing axons, which express ROBO3 isoform ROBO3.2 are not repelled by NELL2, despite interaction between ROBO3.2 and NELL2. NELL1 can also bind to both ROBO3.1 and ROBO3.2, but since NELL1 is not expressed in mouse spinal cord during commissural axon guidance, these interactions are not considered to be physiologically relevant. ROBO1 and ROBO2 do not interact with NELL proteins (Jaworski et al. 2015).