EphB receptors and ephrin-B3 regulate axon guidance at the ventral midline of the embryonic mouse spinal cord.
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-B3(lacz) 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.
Kadison
Stephanie R
SR
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA. skadison@umich.edu
Mäkinen
Taija
T
Klein
Rüdiger
R
Henkemeyer
Mark
M
Kaprielian
Zaven
Z
D000818:Animals; D001369:Axons / Q000502:physiology*; D002232:Carbocyanines; D004622:Embryo, Mammalian / Q000502:physiology; D036389:Ephrin-B3 / Q000235:genetics / Q000502:physiology*; D005456:Fluorescent Dyes; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000196:embryology; D036081:Receptors, Eph Family / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology*; D009435:Synaptic Transmission
D002232:Carbocyanines; D036389:Ephrin-B3; D005456:Fluorescent Dyes; C024286:3,3'-dioctadecylindocarbocyanine; D036081:Receptors, Eph Family