For the nervous system to function, signals are conducted and transmitted in neuronal circuits that reflect the pattern of connections between the cells. The formation of these innervation patterns during development requires the following cellular phenomena; axon elongation, guidance of axon growth and target recognition. The long term goal of this research is to understand these at the molecular level. Axon elongation is a highly specialized task and it is likely that there are molecules whose main function is to mediate this growth. Such molecules might only be present in the neuron when it is growing an axon during embryonic development of during axon regeneration in adults. A monoclonal antibody (MAb) has been produced that binds to such a protein. The molecular characteristics, the function and the mechanisms regulating cellular levels of this molecule will be studied. For a growing axon to reach the vicinity of its target there must be cues in the environment which guide its growth. The first axons in the insect leg grow proximally in response to cues in the extracellular matrix/basement membrane. It has been hypothesized that such cues are distributed in a gradient along the proximal-distal axis of the leg. MAbs have been produced that bind to antigens with such a distribution. The molecular characteristics and function of these antigens will be studied. The existence of target recognition implies that there are biochemical distinctions among the various neurons and targets. MAbs have been produced that bind to the surfaces of axon terminals of some neurons and not others. These candidate neuronal recognition molecules will be biochemically characterized, their function determined and used to study the role of target recognition in axon regeneration. These experiments are done in the neuromuscular system of the cockroach, Periplaneta americana. This has been an excellent model system. Its relatively simple structure and extreme immunogenicity have enabled the production of the immunological probes to an unusual and interesting set of molecules. Because the molecular bases of these developmental events are likely to be similar in vertebrate neurons, a search for homologous molecules will be made. Information on axon elongation and target recognition are relevant to attempts to increase the probability of obtaining successful axon regeneration in humans. Such knowledge would also be helpful for the treatment of paraplegia, neuromuscular disorders, multiple sclerosis and other neurological disorders involving injury such as strokes and head injury.
Showing the most recent 10 out of 15 publications
