The normal functioning of an animal's limb depends on a highly ordered pattern of connections between motoneurons in the spinal cord and the various muscles of the limb. This pattern is established during development by specific axonal growth. Motoneuron axons normally make a series of pathway choices as they grow from the spinal cord to their target muscle. These choices require axons to recognize and respond appropriately to multiple growth cues associated with cells whose precise location and identity are presently unknown in any vertebrate. A combination of various surgical manipulations and several anatomical techniques will be used to localize and to identify the cell populations which provide the environmental cues to guide growing motor axons to their target muscles. All of the experiments will be done on chick or quail embryos. The first question is whether the cues for the two axes of the limb are separately located along the nerve pathways. Other experiments will determine whether the presence of muscle cells, the targets of motoneurons, are required for accurate pathfinding, or whether connective tissue cells are sufficient. The final series of experiments will explore the role of presumptive sheath cells, or Schwann cells, in assuring normal innervation of limb muscles. An increased knowledge of the location and cellular identity of guidance cues used by growing axons during normal development should aid efforts to understand neuromuscular disorders as well as to promote specific regrowth of adult nervous tissue following damage due either to disease or injury.