Moderate to severe hypoplasia and misrouting of the corticospinal tract (CST) in adult Sema6A mutants. (a-c) Macroscopic view of the ventral medulla in adult Sema6A+/- and Sema6A-/- animals. The pyramidal tracts are visible as heavily myelinated structures on either side of the midline (black arrowheads in (a, c)). Red arrows show levels of sections in (d-l): 1 (d-f); 2 (g-i); 3 (j-l). (d-l) PLAP-stained cross-sections from the same brains at indicated levels. In the Sema6A+/- brain (a, d, g, j), the pyramidal tracts run close to the midline at the ventral surface of the medulla (black arrowhead in (a, d)) and disappear from macroscopic view at the level of the decussation, where they turn dorsally (black arrow in (g)) to enter the dorsal funiculus (white arrowhead in (j)). The middle column (b, e, h, k) shows an example of a Sema6A mutant with severe hypoplasia of the CST. In these severe cases the CST is not visible as the medullar pyramids macroscopically (b). Within the medulla the few remaining axons do not run at the surface but deeper, embedded within the inferior olive (black arrowhead in (e)). These fibres mostly decussate correctly (black arrow in (h)) and enter the dorsal funiculus of the spinal cord (white arrowhead in (k)). The right column (c, f, i, l) shows another mutant where the size of the pyramids is reduced to different degrees on either side, but remains visible macroscopically as a tight bundle at the surface (black arrowheads in (c, f)). At the caudal olive the majority of axons track away from the midline and are midway towards the lateral border at the level of the decussation (black arrowheads in (c); asterisks, green arrowheads in (i)). Here they do not decussate but proceed down the spinal cord in a ventrolateral position (asterisks in (l)). A small portion of CST axons that remain close to the midline up to the level of decussation cross contralaterally and dorsally (black arrow in (i)). Scale bars 500 μm: the bar in (c) is for (a-c); the bar in (i) is for (d-i); the bar in (l) is for (j-l).