Model of PlxnA2-Sema6B interactions in commissural axon guidance. (A) In the dorsal spinal cord, pre-crossing axons do not yet express Sema6B. However, axons are not affected by the low levels of repulsive signals (blue diamond) and readily grow towards the ventral midline. Note that we have drawn PlxnA2 (green) arbitrarily as dimer or monomer based on reports on the crystal structures of Sema6A and PlxnA2 (for details see Janssen et al., 2010; Nogi et al., 2010). For simplicity, we omitted neuropilins, which would form complexes with plexins. (B) In the ventral spinal cord, close to the floorplate, where repulsive class-3 semaphorin activity is high (large blue diamond), PlxnA2 (green) is prevented from mediating a repulsive signal due to the cis-interaction with Sema6B (red). (C) At the contralateral floorplate border, post-crossing commissural axons can respond to repulsive class-3 semaphorins, in agreement with published reports (Parra and Zou, 2010; Nawabi et al., 2010), as the cis-interaction of axonal PlxnA2 with Sema6B is replaced by a Sema6B-PlxnA2 trans-interaction. Trans-interactions between floorplate PlxnA2 and growth cone Sema6B result in a turning response and support elongation of post-crossing axons along the contralateral floorplate border.