Figure 3: Axon-axon interactions in the development of callosal axons. (a) Navigation of callosal axons by “pioneer” neurons. Pioneer neurons, which are located in the region extending from the presumptive cingulate cortex to the hippocampus, first extend their axons to form the path of the commissural axons. Then, on E17.0, the most early “follower” axons originating from layer V follow the pioneer neurons. (b) Interaction between the medial and lateral cortex-derived callosal axons through EphA3. The axons from the medial (roughly corresponding to the cingulate, motor and medial part of the primary somatosensory cortices) and lateral cortices (roughly corresponding to the areas around the secondary somatosensory cortex) pass through the dorsal and ventral half of the CC, respectively. Repulsive effects between the medial and lateral cortical axons contribute to their correct pathfinding in the CC. EphA3 expressed on the lateral axons mediates, at least in part, this interaction between the medial and lateral axons.