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Semaphorin III can repulse and inhibit adult sensory afferents in vivo

Nature Medicine volume 3, pages 1398–1401 (1997)Cite this article

Abstract

During development, semaphorins (collapsin, fasciclin) mediate repulsive and inhibitory guidance of neurons1–4. Semaphorin III, a secretable member of this family, is expressed by the ventral spinal cord at the time corresponding to projection of sensory afferents from the dorsal root ganglion (DRG) into the spinal cord6. The inhibitory effect of E14 ventral cord is active only on nerve growth factor (NGF)-responsive sensory afferents (smalldiameter A-delta and C fibers subserving sensations of temperature and pain)5. Similarly, COS cells secreting recombinant semaphorin III are able to selectively repel DRG afferents whose growth is stimulated by NGF and not NT-3 (ref. 7). However, it is not known whether these molecules can exert a functional role in the fully developed adult peripheral nervous system. In this study, we demonstrated that gene gun transfection and production of semaphorin III in corneal epithelial cells in adult rabbits in vivo can cause repulsion of established A-delta and C fiber trigeminal sensory afferents. In addition, it is shown that, following epithelial wounding and denervation, semaphorin III is able to inhibit collateral nerve sprouts from innervating the reepithelialized tissue. These findings are significant in that they provide direct evidence that small-diameter adult sensory neurons retain the ability to respond to semaphorin III. In addition, the corneal gene gun technique may be generally used to study the in vivo effects of neural growth modulators by quantifying the amount of sensory nerve growth.

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Authors and Affiliations

  1. The Eugene McDermott Center for Pain Management, Department ofAnesthesiology and Pain Management and Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75235-9068, USA

    Darrell L. Tanelian, Thuy Le & George M. Smith

  2. Molecular Cardiology Laboratories, Department of Internal Medicine and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75235-9068, USA

    Michael A. Barry & Stephen Albert Johnston

  3. Center for Gene Therapy, Departments of Molecular and Human Genetics and Microbiology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Michael A. Barry

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  1. Darrell L. Tanelian
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  2. Michael A. Barry
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  4. Thuy Le
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  5. George M. Smith
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Tanelian, D., Barry, M., Johnston, S. et al. Semaphorin III can repulse and inhibit adult sensory afferents in vivo. Nat Med 3, 1398–1401 (1997). https://doi.org/10.1038/nm1297-1398

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