Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers

Motor axons form topographic maps on muscles: rostral motor pools innervate rostral muscles, and rostral portions of motor pools innervate rostral fib ers within their targets. Here, we implicate A subfamily ephrins in this to pographic mapping. First, developing muscles express all five of the ephrin -A genes. Second, rostrally and caudally derived motor axons differ in sens itivity to outgrowth inhibition by ephrin-A5. Third, the topographic map of motor axons on the gluteus muscle is degraded in transgenic mice that over express ephrin-A5 in muscles. Fourth, topographic mapping is impaired in mu scles of mutant mice lacking ephrin-A2 plus ephrin-A5. Thus, ephrins mediat e or modulate positionally selective synapse formation. In addition, the ro strocaudal position of at least one motor pool is altered in ephrin-A5 muta nt mice, indicating that ephrins affect nerve-muscle matching by intraspina l as well as intramuscular mechanisms.