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

Neuron. 2000 Feb;25(2):295-306. doi: 10.1016/s0896-6273(00)80895-8.


Motor axons form topographic maps on muscles: rostral motor pools innervate rostral muscles, and rostral portions of motor pools innervate rostral fibers within their targets. Here, we implicate A subfamily ephrins in this topographic mapping. First, developing muscles express all five of the ephrin-A genes. Second, rostrally and caudally derived motor axons differ in sensitivity to outgrowth inhibition by ephrin-A5. Third, the topographic map of motor axons on the gluteus muscle is degraded in transgenic mice that overexpress ephrin-A5 in muscles. Fourth, topographic mapping is impaired in muscles of mutant mice lacking ephrin-A2 plus ephrin-A5. Thus, ephrins mediate or modulate positionally selective synapse formation. In addition, the rostrocaudal position of at least one motor pool is altered in ephrin-A5 mutant mice, indicating that ephrins affect nerve-muscle matching by intraspinal as well as intramuscular mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / chemistry
  • Axons / physiology
  • Cell Communication / drug effects
  • Cell Communication / genetics
  • Cells, Cultured
  • Ephrin-A2
  • Ephrin-A5
  • Fibroblasts / cytology
  • Gene Expression / physiology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Motor Neurons / chemistry
  • Motor Neurons / cytology*
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / cytology*
  • Muscle, Skeletal / cytology
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism
  • Spinal Cord / cytology
  • Synapses / drug effects
  • Synapses / physiology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology


  • Ephrin-A2
  • Ephrin-A5
  • Membrane Proteins
  • Transcription Factors