Slit2-mediated chemorepulsion and collapse of developing forebrain axons

Diffusible chemorepellents play a major role in guiding developing axons to ward their correct targets by preventing them from entering or steering the m away from certain regions. Genetic studies in Drosophila revealed a novel repulsive guidance system that prevents inappropriate axons from crossing the CNS midline; this repulsive system is mediated by the Roundabout (Robo) receptor and its secreted ligand Slit. In rodents, Robe and Slit are expre ssed in the spinal cord and Slit can repel spinal motor axons in vitro. Her e, we extend these findings into higher brain centers by showing that Robo1 and Robo2, as well as Slit1 and Slit2, are often expressed in complementar y patterns in the developing forebrain. Furthermore, we show that human Sli t2 can repel olfactory and hippocampal axons and collapse their growth cone s.