Novel Repellent Activity of Motor Neurons in Commissural Axon Guidance BISC 494 Honors Thesis

During embryonic development, commissural axons, originating in the dorsal spinal cord, send axons ventrally towards the floor plate. The trajectory of these axons is mediated by both repulsive cues secreted from the roof plate, as well as attractive cues secreted from the floor plate. To investigate the guidance activity of the floor plate, we first attempted to examine the role of Sonic Hedgehog (Shh), a proposed chemoattractant in commissural axon guidance, by misexpressing Shh in chick embryos. While our misexpression experiments showed strong misexpression, we were unable to evaluate Shh’s role as a guidance cue due to drastic changes in spinal cord patterning. We then took a different approach and examined commissural axon trajectory in the absence of guidance cues from the floor plate. By analyzing the Gli2 mouse, which lacks a floor plate, we found that commissural axon trajectories become highly disorganized as they project through the medially and ventrally shifted population of motor neurons. Further investigation of the interaction between commissural axons and motor neurons revealed that commissural axons avoid areas rich in motor neurons and favor regions with few motor neurons as they navigate towards the ventral midline. Thus we propose motor neurons possess a repellent activity that facilitates the guidance of commissural axons in the ventral spinal cord.