A series of reciprocal interactions between developing neurons and Schwann cells leads to formation of peripheral nerve trunks and culminates in ensheathment of axons and myelin formation. Schwann cells have been proposed to play an essential role in guidance of axons to targets during regeneration of peripheral nerves and may provide guidance cues to developing axons. However, little is known about early axon Schwann cell interactions. Unresolved questions include the exact lineage relationship between the ensheathing cells and the motor and sensory neurons of peripheral nerves, the time and place of these cells' first encounter, and the molecules involved in their recognition and adhesion. We plan to address these issues by identifying and characterizing molecules that mediate the initial adhesion between Schwann cells and axons, by developing markers specific for Schwann cell precursors and using them to describe the path followed by these cells as they migrate to the periphery, and by determining if Schwann cells and the neurons they ensheath are derived from a common precursor. In longer range studies we will evaluate the role of Schwann cells in the development of peripheral nerves by using adhesion-blocking antibodies to perturb axon-Schwann cell interactions. These studies will use biochemical and immunological methods of protein purification, immunohistochemical analysis at the light and, electron microscopic levels, and retrovirus vector lineage markers. While the proposed research focuses on basic issues in the normal development of peripheral nerves, the findings may provide useful insights into our understanding of both demyelinating disease and nerve regeneration.
