How neurons make synaptic connections with the correct cells during the development of the nervous system is still largely a mystery. It is clear that the guidance of growing nerve cell processes (axons) to appropriate regions of the developing nervous system, where their future target cells reside, places constraints on which neurons can ultimately connect with each other. However, even within a small region there exist neurons with very different functions, and growing nerve axons must be able to recognize these different neuronal types and choose only the ones appropriate for them to make connections with. This project will examine the mechanisms by which neurons that normally innervate muscle fibers (motoneurons) discriminate between different muscles. One possibility is that each muscle is unique in some way that motoneurons axons can recognize. A way to achieve this would be for muscle fibers to carry a molecular label of some kind that distinguishes them from muscle fibers in other muscles. Dr. Wigston will examine this possibility by searching for molecules unique to, or highly concentrated in, a particular muscle, by generating monoclonal antibody probes that bind selectively to particular muscles. Another possibility is that each muscle secretes its own diffusible factor that attracts the axons of only those motoneurons appropriate for that muscle. This possibility will be examined by culturing pieces of spinal cord and muscle near to one another, and determining whether particular axons grow preferentially towards particular muscles. Furthermore, using various experimental designs, isolated motoneurons will be grown in tissue culture and their selectivity for different muscles examined. If selective synapse formation occurs in such a system, it will provide tremendous opportunities for the elucidation of the mechanism by which selectivity is achieved. This work should help us to understand how the correct "wiring pattern" is laid down in the developing neurons system, and in particular how the right motoneurons connect with the right muscles during embryogenesis. The normal functioning of the brain, and normal behavior of the organism, is critically dependent on the establishment of proper orderly neuronal connectivity.
