Growth cone repulsion is an important mechanism controlling axon growth. During development it guides axons by excluding them from repulsive regions of the embryo. Following injury to the adult brain it may also block axon regeneration, with major clinical consequences. Our laboratory is investigating two axon-repulsive systems. We are characterizing somite glycoproteins that repel axons, creating the segmented pattern of spinal nerves during development. We have also purified a repulsive protein in the grey matter of the adult brain that may contribute to CNS regenerative failure. Besides elucidating the biology of these molecules and their receptors, an important clinical aim is to interfere with their inhibitory action, including the use of engineered bacterial chondroitinase, to see whether improved functional regeneration can be achieved using models of brain and spinal cord injury.