EphB receptors and ephrin-B3 regulate axon guidance at the ventral midline of the embryonic mouse spinal cord

Stephanie R. Kadison, Taija Mäkinen, Rüdiger Klein, Mark Henkemeyer, Zaven Kaprielian

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


EphB receptors and their ephrin-B ligands are required for midline guidance decisions at several rostrocaudal levels of the developing CNS. In the embryonic vertebrate spinal cord, ephrin-B3 is localized to the floor plate (FP) at the ventral midline (VM), ephrin-B1 and ephrin-B2 are expressed in the dorsal spinal cord, and decussated EphB receptor-bearing commissural axons navigate between these ventral and dorsal ephrin-B domains. Despite these compelling expression patterns, the in vivo role(s) for EphB and ephrin-B proteins in regulating the guidance of spinal commissural axons has not been established. Here, we use DiI (1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine perchlorate) labeling to assess the pathfinding of commissural axons in the spinal cords of ephrin-B and EphB mutant mouse embryos. In mice lacking ephrin-B3 or multiple EphB receptors, a significant number of axons followed aberrant trajectories in the immediate vicinity of the VM. Furthermore, forked transverse commissural (FTC) axons, a unique class of commissural axons that continues to project in the transverse plane on the contralateral side of the FP, were present at a markedly higher frequency in ephrin-B3 and EphB mutants, compared with wild-type embryos. Neither the midline guidance errors nor excessive numbers of FTC axons were observed in the spinal cords of ephrin-B3lacz mice that express a truncated form of ephrin-B3, which is capable of forward but not reverse signaling. In contrast to the midline guidance defects observed in EphB and ephrin-B3 mutant embryos, wild-type-like contralateral projections were observed in mice lacking ephrin-B1 and/or ephrin-B2.

Original languageEnglish (US)
Pages (from-to)8909-8914
Number of pages6
JournalJournal of Neuroscience
Issue number35
StatePublished - Aug 30 2006


  • Commissural axon
  • EphB
  • Ephrin-B
  • Floor plate
  • Mouse embryo
  • Spinal cord
  • Ventral midline

ASJC Scopus subject areas

  • Neuroscience(all)


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