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Ephrin contribution to myelin‐based inhibition of axonal regeneration
Author(s) -
Benson M. Douglas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.173.1
Subject(s) - ephrin , myelin , axon , neuroscience , biology , oligodendrocyte , neurite , microbiology and biotechnology , population , inhibitory postsynaptic potential , myelin associated glycoprotein , regeneration (biology) , corticospinal tract , central nervous system , signal transduction , biochemistry , in vitro , medicine , environmental health , radiology , diffusion mri , magnetic resonance imaging
The inability of central nervous system axons to regenerate after traumatic spinal cord injury (SCI) is due, in large 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, and all transduce their inhibitory signals through the same Nogo receptor/p75 neurotrophin receptor/LINGO‐1 (NgR1/p75/LINGO‐1) complex. In mice, ephrin‐B3 functions during development as a midline repellant for axons of the corticospinal tract (CST), which signal through the axonally expressed EphA4 receptor tyrosine kinase. We demonstrated that ephrin‐B3 is expressed in postnatal myelinating oligodendrocytes and accounts for an inhibitory activity toward EphA4‐bearing axons equivalent to that of the other three myelin‐based inhibitors, acting through p75, combined. Our data were the first description of a known vertebrate axon guidance molecule as a myelin‐based inhibitor of neurite outgrowth. They suggest that susceptibility of a given population of axons to myelin inhibition of regeneration may vary depending on the complement of receptors expressed by that population. Our ongoing studies are determining the extent to which blockage of ephrin‐B3 in vivo can be used to increase regrowth of the functionally critical CST.