INHIBITORY MOLECULES IN DEVELOPMENT AND REGENERATION

In addition to chemotrophic and contact guidance theories that explain how long projection neurons weave intricate patterns of connectivity within developing or regenerating neuronal networks, there has been recent interest in mechanisms that guide axons by actively constraining, inhibiting or repelling axon growth cones. Developmental boundaries are especially important in regions where large numbers of growing axons must change direction in order to remain on course towards their potential targets. Regenerative boundaries can also have severe pathological consequences since they limit the potential for axon regrowth following injury or diseases. Some of the molecular mechanisms that generate repulsive environments in the embryo are re-expressed in the adult following injury. In the developing retina, a chondroitin sulfate-proteoglycan appears to play an essential role in controlling the sequence of ganglion cell differentiation and initial direction of axons. In several lesion models, re-expression of a chondroitin sulfate-proteoglycan by reactive astrocytes limits regeneration through glial scars; conversely, in experiments where boundary molecules have been manipulated by chondroitinase digestion, axons are stimulated to regrow or reroute to inappropriate pathways.