Forward signaling mediated by ephrin-B3 prevents contralateral corticospinal axons from recrossing the spinal cord midline

Nobuhiko Yokoyama, Mario I. Romero, Chad A. Cowan, Pedro Galvan, Françoise Helmbacher, Patrick Charnay, Luis F. Parada, Mark Henkemeyer

Research output: Contribution to journalArticle

170 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)85-97
Number of pages13
JournalNeuron
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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