There is much experimental evidence supporting the hypothesis that peripheral nerves contain extracellular molecules that support the regenerative efforts of disrupted neuronal axons. Experiments in vitro have identified molecules that promote neurite regrowth from cultured neurons. We have recently been successful in producing a monoclonal antibody which directly interferes with the activity of a heparan sulfate proteoglycan complex which promotes neurite growth in culture. This antibody stains the Schwann cell basal lamina in normal peripheral nerves and in the distal stump of severed peripheral nerves, whereas it does not stain CNS tracts in spinal cord, cerebellum, or optic nerve. Thus, this antigen is likely to play a role in nerve regeneration. By the use of novel immunological techniques developed in our laboratory, we propose to identify, characterize, and localize the extracellular molecules which underlie the successful regeneration of axons in the peripheral nervous system. The possibility exists that the absence of these molecules in adult mammalian CNS explains the failure of axonal regeneration in this tissue. Since embryonic mammalian CNS tissue appears to support effective axonal elongation these molecules may have been present in the vicinity of growing central axons during development. Finally, several experiments have demonstrated that neurotrophic activities are induced in denervated target tissue (Ebendal et al.) and in the distal stump of severed periopheral nerve (Richardson et al.). For these reasons, monoclonal antibodies which identify antigens that display one or more of the following properties will be sought: 1. present in peripheral nerves but absent from CNS tissue. 2. present in embryonic CNS tissue but absent from adult CNS tissue. 3. induced in the distal stump of severed peripheral nerves. These antibodies will subsequently be tested for their ability to interfere with axonal regeneration in an in vitro neurite extension bioassay. Ultimately, all of the antibodies which inhibit axonal regrowth in vitro will be tested for their ability to do so in vivo.
