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 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.
Feng
G
G
Department of Anatomy, Washington University Medical School, St. Louis, Missouri 63110, USA.
Laskowski
M B
MB
Feldheim
D A
DA
Wang
H
H
Lewis
R
R
Frisen
J
J
Flanagan
J G
JG
Sanes
J R
JR
D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D036383:Ephrin-A2; D036386:Ephrin-A5; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009046:Motor Neurons / Q000737:chemistry / Q000166:cytology*; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology*; D018482:Muscle, Skeletal / Q000166:cytology; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D036383:Ephrin-A2; D036386:Ephrin-A5; D008565:Membrane Proteins; D014157:Transcription Factors