Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury
Edited by Joshua R. Sanes, Harvard University, Cambridge, MA, and approved February 16, 2012 (received for review August 25, 2011)
Abstract
Recovery of neurological function after traumatic injury of the adult mammalian central nervous system is limited by lack of axonal growth. Myelin-derived inhibitors contribute to axonal growth restriction, with ephrinB3 being a developmentally important axonal guidance cue whose expression in mature oligodendrocytes suggests a role in regeneration. Here we explored the in vivo regeneration role of ephrinB3 using mice lacking a functional ephrinB3 gene. We confirm that ephrinB3 accounts for a substantial portion of detergent-resistant myelin-derived inhibition in vitro. To assess in vivo regeneration, we crushed the optic nerve and examined retinal ganglion fibers extending past the crush site. Significantly increased axonal regeneration is detected in ephrinB3−/− mice. Studies of spinal cord injury in ephrinB3−/− mice must take into account altered spinal cord development and an abnormal hopping gait before injury. In a near-total thoracic transection model, ephrinB3−/− mice show greater spasticity than wild-type mice for 2 mo, with slightly greater hindlimb function at later time points, but no evidence for axonal regeneration. After a dorsal hemisection injury, increased corticospinal and raphespinal growth in the caudal spinal cord are detected by 6 wk. This increased axonal growth is accompanied by improved locomotor performance measured in the open field and by kinematic analysis. Thus, ephrinB3 contributes to myelin-derived axonal growth inhibition and limits recovery from adult CNS trauma.
Acknowledgments
We thank Noam Harel for advice regarding Simi video gait kinematics. This work was supported by grants from The Christopher and Dana Reeve Foundation, the Wings for Life Foundation, The Dr. Ralph and Marion Falk Medical Research Trust, and the National Institutes of Health (to M.H., W.B.J.C., and S.M.S.).
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Cover image: Pictured is a spotted hyena, a carnivorous mammal that roams the deserts and grasslands of Africa. Peihua Jiang et al. identified sequence-disrupting mutations in a hyena gene that encodes a receptor protein responsible for the perception of sweet taste among mammals. The authors report that mutations in the gene might explain why hyenas are the most carnivorous members of their family of mammals; the mutations turn the genes into dysfunctional versions called pseudogenes. The authors detected similar mutations in the taste receptors of seven other exclusively meat-eating species of mammals, hinting at the extent of the loss of taste perception among carnivores. See the article by Jiang et al. on pages 4956–4961. Image courtesy of Richard G. Fisher, Wilmette, IL.
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Published online: March 12, 2012
Published in issue: March 27, 2012
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Acknowledgments
We thank Noam Harel for advice regarding Simi video gait kinematics. This work was supported by grants from The Christopher and Dana Reeve Foundation, the Wings for Life Foundation, The Dr. Ralph and Marion Falk Medical Research Trust, and the National Institutes of Health (to M.H., W.B.J.C., and S.M.S.).
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This article is a PNAS Direct Submission.
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The authors declare no conflict of interest.
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