Selective innervation of transplanted limb muscles by regenerating motor axons in the axolotl.

The segmental pattern of motor innervation of hindlimb muscles in the axolotl was studied before and after reinnervation. To ascertain the specificity of reinnervation, the four spinal nerves innervating the hindlimb were severed and allowed to regenerate. The segmental origin of axons reinnervating particular muscles was then determined by intracellular recording from muscle fibers. Muscles were reinnervated in a specific manner: From the outset, the axons reinnervating each muscle originated largely from segmentally appropriate spinal nerves in the proper proportions, suggesting that a reliable mechanism of selective synapse regeneration exists even in mature axolotls. To examine the selectivity of reinnervation, individual muscles were transplanted to novel positions within the limb and the specificity of their reinnervation determined. Even after being moved to new positions, muscles were reinnervated for the most part by axons of appropriate segmental origin. Therefore, cues must exist on or within limb muscles that regenerating motor axons recognize and use to discriminate between different muscles during synapse formation. These results suggest that one of the mechanisms that promote the reestablishment of correct connections during reinnervation of axolotl limbs may be the selective formation of synapses with appropriate target cells.