PT - JOURNAL ARTICLE AU - Kadison, Stephanie R. AU - Mäkinen, Taija AU - Klein, Rüdiger AU - Henkemeyer, Mark AU - Kaprielian, Zaven TI - EphB Receptors and Ephrin-B3 Regulate Axon Guidance at the Ventral Midline of the Embryonic Mouse Spinal Cord AID - 10.1523/JNEUROSCI.1569-06.2006 DP - 2006 Aug 30 TA - The Journal of Neuroscience PG - 8909--8914 VI - 26 IP - 35 4099 - http://www.jneurosci.org/content/26/35/8909.short 4100 - http://www.jneurosci.org/content/26/35/8909.full SO - J. Neurosci.2006 Aug 30; 26 AB - 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.