RT Journal Article
SR Electronic
T1 EphB Receptors and Ephrin-B3 Regulate Axon Guidance at the Ventral Midline of the Embryonic Mouse Spinal Cord
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8909
OP 8914
DO 10.1523/JNEUROSCI.1569-06.2006
VO 26
IS 35
A1 Kadison, Stephanie R.
A1 Mäkinen, Taija
A1 Klein, Rüdiger
A1 Henkemeyer, Mark
A1 Kaprielian, Zaven
YR 2006
UL http://www.jneurosci.org/content/26/35/8909.abstract
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.