Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth

M. Douglas Benson, Mario I. Romero, Mark E. Lush, Q. Richard Lu, Mark Henkemeyer, Luis F. Parada

Research output: Contribution to journalArticle

232 Scopus citations

Abstract

The inability of CNS axons to regenerate after traumatic spinal cord injury is due, in part, to the inhibitory effects of myelin. The three major previously identified constituents of this activity (Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein) were isolated based on their potent inhibition of axon outgrowth in vitro. All three myelin components transduce their inhibitory signals through the same Nogo receptor/p75 neurotrophin receptor/LINGO-1 (NgR1/p75/LINGO-1) complex. In this study, we considered that molecules known to act as repellants in vertebrate embryonic axonal pathfinding may also inhibit regeneration. In mice, ephrin-B3 functions during development as a midline repellant for axons of the corticospinal tract. We therefore investigated whether this repellant was expressed in the adult spinal cord and retained inhibitory activity. We demonstrate that ephrin-B3 is expressed in postnatal myelinating oligodendrocytes and, by using primary CNS neurons, show that ephrin-B3 accounts for an inhibitory activity equivalent to that of the other three myelin-based inhibitors, acting through p75, combined. Our data describe a known vertebrate axon guidance molecule as a myelin-based inhibitor of neurite outgrowth.

Original languageEnglish (US)
Pages (from-to)10694-10699
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number30
DOIs
StatePublished - Jul 26 2005

Keywords

  • Axon
  • Eph receptor
  • Regeneration
  • Spinal cord injury

ASJC Scopus subject areas

  • General

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