An Oligodendrocyte Lineage-Specific Semaphorin, Sema5A, Inhibits Axon Growth by Retinal Ganglion Cells

In the mammalian CNS, glial cells repel axons during development and inhibit axon regeneration after injury. It is unknown whether the same repulsive axon guidance molecules expressed by glia and their precursors during development also play a role in inhibiting regeneration in the injured CNS. Here...

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Bibliographic Details
Published in:The Journal of neuroscience 2004-05, Vol.24 (21), p.4989-4999
Main Authors: Goldberg, Jeffrey L, Vargas, Mauricio E, Wang, Jack T, Mandemakers, Wim, Oster, Stephen F, Sretavan, David W, Barres, Ben A
Format: Article
Language:English
Subjects:
Animals
Axons - physiology
Cells, Cultured
Development/Plasticity/Repair
Growth Cones - physiology
Growth Inhibitors - metabolism
Membrane Proteins - isolation & purification
Membrane Proteins - pharmacology
Membrane Proteins - physiology
Nerve Regeneration - physiology
Nerve Tissue Proteins - isolation & purification
Nerve Tissue Proteins - pharmacology
Nerve Tissue Proteins - physiology
Neuroglia - metabolism
Oligodendroglia - cytology
Oligodendroglia - physiology
Optic Nerve - metabolism
Rats
Rats, Sprague-Dawley
Receptors, Growth Factor - metabolism
Retinal Ganglion Cells - metabolism
Semaphorins - isolation & purification
Semaphorins - metabolism
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Summary:In the mammalian CNS, glial cells repel axons during development and inhibit axon regeneration after injury. It is unknown whether the same repulsive axon guidance molecules expressed by glia and their precursors during development also play a role in inhibiting regeneration in the injured CNS. Here we investigate whether optic nerve glial cells express semaphorin family members and, if so, whether these semaphorins inhibit axon growth by retinal ganglion cells (RGCs). We show that each optic nerve glial cell type, astrocytes, oligodendrocytes, and their precursor cells, expressed a distinct complement of semaphorins. One of these, sema5A, was expressed only by purified oligodendrocytes and their precursors, but not by astrocytes, and was present in both normal and axotomized optic nerve but not in peripheral nerves. Sema5A induced collapse of RGC growth cones and inhibited RGC axon growth when presented as a substrate in vitro. To determine whether sema5A might contribute to inhibition of axon growth after injury, we studied the ability of RGCs to extend axons when cultured on postnatal day (P) 4, P8, and adult optic nerve explants and found that axon growth was strongly inhibited. Blocking sema5A using a neutralizing antibody significantly increased RGC axon growth on these optic nerve explants. These data support the hypothesis that sema5A expression by oligodendrocyte lineage cells contributes to the glial cues that inhibit CNS regeneration.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4390-03.2004