DCC and ROBO1 heterodimerize via conserved sequence elements in their cytoplasmic domains, namely CC1 (conserved cytoplasmic region1) in ROBO1 and P3 in DCC. The formation of this complex is dependent on the previous interaction between ROBO and its ligand (SLIT). This physical interaction between ROBO:SLIT and DCC silences the attractive effect of Netrin:DCC and regulates the midline crossing of axons.
From the analysis of multiple double mutant combinations of the ROBO:SLIT and Netrin:DCC receptor-ligand pairs, it was deduced that ROBO repulsion on its own is sufficient to prevent commissural axons from re-crossing the midline, and that Netrin:DCC is not the only source of attraction at the midline (Garbe and Bashaw 2007).