Forward signaling mediated by ephrin-B3 prevents contralateral corticospinal axons from recrossing the spinal cord midline.
To investigate Eph-ephrin bidirectional signaling, a series of mutations were generated in the ephrin-B3 locus. The absence of both forward and reverse signaling resulted in mice with mirror movements as typified by a hopping locomotion. The corticospinal tract was defective as axons failed to respect the midline boundary of the spinal cord and bilaterally innervated both contralateral and ipsilateral motor neuron populations. A second mutation that expresses a truncated ephrin-B3 protein lacking its cytoplasmic domain did not lead to hopping, indicating that reverse signaling is not required for corticospinal innervation. Ephrin-B3 is concentrated at the spinal cord midline, while one of its receptors, EphA4, is expressed in postnatal corticospinal neurons as their fibers pathfind down the contralateral spinal cord. Our data indicate ephrin-B3 functions as a midline-anchored repellent to stimulate forward signaling in EphA4-expressing axons.
Yokoyama
N
N
Center for Developmental Biology and, Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Romero
M I
MI
Cowan
C A
CA
Galvan
P
P
Helmbacher
F
F
Charnay
P
P
Parada
L F
LF
Henkemeyer
M
M
D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D004558:Electric Stimulation; D036389:Ephrin-B3; D005260:Female; D005326:Fetal Proteins / Q000096:biosynthesis; D020233:Gait Disorders, Neurologic / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D006720:Homozygote; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009044:Motor Cortex / Q000503:physiopathology; D016297:Mutagenesis, Site-Directed; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D036122:Receptor, EphA4; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D036389:Ephrin-B3; D005326:Fetal Proteins; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036122:Receptor, EphA4