Fig. 3

Summary of ventral midline crossing. a In the vertebrate spinal cord, dorsal commissural neurons extend their axons ventrally. They are guided first by the roof plate (RP)-chemorepellent, mediated by the Bmps acting through BmprIb, that directs them away from the dorsal midline. Commissural axons are then directed towards the floor plate at the ventral midline, considered a classic example of an axon guidance guidepost, by action of two attractants, netrin1 and Shh, in a Dcc- and Smo/Boc-dependent mechanism, respectively. b Midline crossing is mediated by the slit/Robo pathway. The floor plate (FP) expresses the slit repellent, which is detected by the robo receptor family. Pre-crossing commissural axons are unresponsive to slit, as a consequence of the expression of Robo3, which interferes with Robo1 function. However, after crossing the midline, Robo3 expression is downregulated, such that Robo1⁺ commissural axons become sensitive to the presence of slit, guiding the axons away from the midline and preventing the axons from re-crossing the midline. c Guidance decisions are largely conserved in the Drosophila nerve cord. Attraction of commissural axons to Netrin1 is mediated by the Dcc homologue Frazzled (Fra). Similarly, Slit proteins regulate behavior of pre and post-midline crossing Robo⁺ axons through repulsive signaling. However, in Drosophila, Robo levels are regulated by Comm, which endocytoses Robo in axons, making them unable to detect slit repulsion, and thereby permits axons to cross the midline