Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb

Neuron. 2008 Dec 26;60(6):1039-53. doi: 10.1016/j.neuron.2008.11.011.


Studies of the innervation of limb muscles by spinal motor neurons have helped to define mechanisms by which axons establish trajectories to their targets. Related motor axons select dorsal or ventral pathways at the base of the limb, raising the question of how these alternate trajectories are specified. EphA signaling has been proposed to control the dorsal trajectory of motor axons in conjunction with other signaling systems, although the respective contributions of each system to motor axon guidance are unclear. We show that the expression of EphB receptors by motor axons, and ephrin-B ligands by limb mesenchymal cells, directs the ventral trajectory of motor axons. Our findings reveal symmetry in the molecular strategies that establish this aspect of nerve-muscle connectivity. The involvement of ephrin:Eph signaling in guiding both sets of motor axons raises the possibility that other signaling systems function primarily to refine or modulate a core Eph signaling program.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Body Patterning / genetics*
  • Chick Embryo
  • Electroporation / methods
  • Embryo, Mammalian
  • Ephrins / deficiency
  • Ephrins / genetics
  • Ephrins / metabolism*
  • Extremities / embryology
  • Extremities / innervation*
  • Gene Expression Regulation, Developmental / physiology
  • Green Fluorescent Proteins / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Horseradish Peroxidase / metabolism
  • LIM-Homeodomain Proteins
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Motor Neurons / cytology*
  • Mutation / physiology
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Eph Family / metabolism
  • Signal Transduction / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Ephrins
  • Homeodomain Proteins
  • LIM homeobox transcription factor 1 beta
  • LIM-Homeodomain Proteins
  • Lhx1 protein, mouse
  • Neurofilament Proteins
  • RNA, Messenger
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1
  • Green Fluorescent Proteins
  • Horseradish Peroxidase
  • Receptors, Eph Family