Abstract
Beginning with the unexpected finding by cDNA array analysis that neuropilin-2 is induced in sciatic nerve distal to a transection, we document, for the first time, up-regulation in the axotomized adult peripheral nervous system of class 3 semaphorins and their receptors, which are known to play prominent roles in axonal guidance during neural development. Previously, we described the use of cDNA arrays to screen for novel peripheral nervous system axotomy-induced candidate neurotrophic proteins. A novel finding of that prior study was substantial induction of neuropilin 2 (NP2) mRNA in the axotomized nerve segments. Following up on that initial observation, we have now used real-time quantitative reverse transcription-polymerase chain reaction to demonstrate induction of genes encoding neuropilin 1 (NP1), which, like NP2, serves as a coreceptor for members of the class 3 semaphorin family of axonal guidance molecules and of five of the six known class 3 semaphorins (Sema3A, Sema3B, Sema3C, Sema3E, and Sema3F, but not Sema3D) in crushed or transected sciatic nerves.
Similar content being viewed by others
References
Aguayo, A., David, S., and Bray, G. 1981. Influences of the glial environment on the elongation of axons after injury: transplantation studies in adult rodents. J. Exp. Biol. 95:231–240.
David, S. and Aguayo, A. 1985. Axonal regeneration after crush injury of rat central nervous system fibres innervating peripheral nerve grafts. J. Neurocytol. 14:1–12.
Guest, J. D., Rao, A., Olsen, L., Bunge, M., and Bunge, R. 1997. The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord. Exp. Neurol. 148:502–522.
Freidman, B., Scherer, S., Rudge, J. S., Helgren, M., Morrisey, D., McClain, J., Wang, D. Y., Wiegand, S. J., Furth, M. E., Lindsay, R. M., et al. 1992. Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo. Neuron 9:295–305.
Sendtner, M., Gotz, R., Hotmann, B., and Thoenen, H. 1997. Endogenous ciliary neurotrophic factor is a lesion factor for axotomized motoneurons in adult mice. J. Neurosci. 17:6999–7006.
Curtis, R., Scherer, S., Somogyi, R., Adryan, K., Ip, N., Zhu, Y., Lindsay, R., and DiStefano, P. 1994. Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve. Neuron 12:191–204.
Meyer, M., Matsuoka, I., Wetmore, C., Olson, L., and Thoenen, H. 1992. Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J. Cell Biol. 119:45–54.
Funakoshi, H., Frisen, J., Barbany, G., Timmusk, T., Zachrisson, O., Verge, M. M., and Perssori, H. 1993. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J. Cell Biol. 123:455–465.
Hoke, A., Gordon, T., Zochodne, D., and Sulaiman, O. 2002. A decline in glial cell-line-derived neurotrophic factor expression is associated with impaired regeneration after long-term Schwann cell denervation. Exp. Neurol. 173:77–85.
Pu, S., Zhuang, H., and Ishii, D. 1995. Differential spatiotemporal expression of the insulin-like growth factor genes in regenerating sciatic nerve. Brain Res. Mol. Brain Res. 34:18–28.
Cheng, H., Randolph, A., Yee, D., Delafontaine, P., Tennekoon, G., and Feldman, E. 1996. Characterization of insulin-like growth factor-I and its receptor and binding proteins in transected nerves and cultured Schwann cells. J. Neurochem. 66:525–536.
Hammarberg, H., Risling, M., Hokfelt, T., Cullheim, S., and Piehl, F. 1998. Expression of insulin-like growth factors and corresponding binding proteins (IGFBP 1-;6) in rat spinal cord and peripheral nerve after axonal injuries. J. Comp. Neurol. 400:57–72.
Scarlato, M., Xu, T., Bannerman, P., Beesley, J., Reddy, U. R., Rostami, A., Scherer, S. S., and Pleasure, D. 2001. Axon-Schwann cell interactions regulate the expression of fibroblast growth factor-5 (FGF-5). J. Neurosci. Res. 66:16–22.
McGeachie, A., Koishi, K., Imamura, T., and McLennan, I. 2001. Fibroblast growth factor-5 is expressed in Schwann cells and is not essential for motoneurone survival. Neuroscience 104:891–899.
Lindholm, D., Heumann, R., Meyer, M., and Thoenen, H. 1987. Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve. Nature 330:658–659.
Saada, A., Dunaevsky-Hutt, A., Aamur, A., Reichert, F., and Rotshenker, S. 1995. Fibroblasts that reside in mouse and frog injured peripheral nerves produce apolipoproteins. J. Neurochem. 64:1996–2003.
Gillen, C., Gleichmann, M., Spreyer, P., and Muller, H. W. 1995. Differentially expressed genes after peripheral nerve injury. J. Neurosci. Res. 42:159–171.
Spreyer, P., Schaal, H., Kuhn, G., Rothe, T., Unterbeck, A., Olek, K., and Muller, H. 1990. Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve. EMBO J. 9:2479–2484.
Scarlato, M., Ara, J., Bannerman, P., Scherer, S. S., and Pleasure, D. 2003. Induction of neuropilins-1 and-2 and their ligands, Sema3A, Sema3F, and VEGF, during Wallerian degeneration in the peripheral nervous system. Exp. Neurol. 183:489–497.
Lemke, G. and Chao, M. 1988. Axons regulate Schwann cell expression of the major myelin and NGF receptor genes. Development 102:499–504.
Mezei, C. 1993. Myelination in the peripheral nerve during development. Pages 267–281, in Dyck, P. J., Thomas, P. K., Low, P. A., and Poduslo, J. F. (eds), Peripheral neuropathology. W. B. Saunders, Philadelphia.
Boyles, J. K., Notterpek, L. M., and Anderson, L. J. 1990. Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve. Identification of apolipoprotein D, apolipoprotein A-IV, apolipoprotein E, and apolipoprotein A-I. J. Biol. Chem. 265:17805–17815.
Chen, H., He, Z., Bagri, A., and Tessier-Lavigne, M. 1998. Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron 21:1283–1290.
Mark, M. D., Lohrum, M., and Puschel, A. W. 1997. Pattering neuronal connections by chemorepulsion: the semaphorins. Cell. Tissue Res. 290:299–306.
Chen, H., Chedotal, A., He, Z., Goodman, C., and Tessier-Lavigne, M. 1997. Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 19:547–559.
He, Z. and Tessier-Lavigne, M. 1997. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90:739–751.
Kolodkin, A. L., Levengood, D. V., Rowe, E. G., Tai, Y. T., Giger, R. J., and Ginty, D. 1997. Neuropilin is a semaphorin III receptor. Cell 90:753–762.
Takahashi, T., Fournier, A., Nakamura, F., Wang, L-H., Murakami, Y., Kalb, R. G., Fujisawa, H., and Strittmatter, S. M. 1999. Plexin-neuropilin-1 complexes from functional semaphorin-3A receptors. Cell 99:59–69.
Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G-L., Song, H-J., Chedotal, A., Winber, M. L., Goodman, C. S., Poo, M-M., Tessier-Lavigne, M., and Comoglio, P. M. 1999. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99:71–80.
Rostami, A., Gregorian, S., Brown, M., and Pleasure, D. 1990. Induction of severe experimental autoimmune neuritis with a synthetic peptide corresponding to the 53-;78 amino acid sequence of the myelin P2 protein. J. Neuroimmunol. 30:145–151.
Kitsukawa, T., Shimizu M., Sanbo, M., Hirata, T., Taniguchi, M., Bekku, Y., Takeshi, Y., and Fujisawa, H. 1997. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 19:995–1005.
Taniguchi, M., Yuasa, S., Fujisawa, H., Naruse, I., Saga, S., Mishina, M., and Yagi, T. 1997. Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 19:519–530.
Giger, R. J., Cloutier, J-F., Sahay, A., Prinjha, S. E., Pickering, S., Simmons, D., Rastan, S., Walsh, F. S., Kolodkin, A. L., Ginty, D. D., and Geppert, M. 2000. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron 25:29–41.
Takahashi, T. and Strittmatter, S. M. 2001. PlexinA1 autoinhibition by the plexin sema domain. Neuron 29:429–439.
Chen, H., Bagri, A., and Tessier-Lavigne, M. 1998. Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron 21:1283–1290.
Raper, J. A. 2000. Semaphorins and their receptors in vertebrates and invertebrates. Curr. Opin. Neurobiol. 10:88–90.
Zou, Y., Stoeckli, E., Chen, H., and Tessier-Lavigne, M. 2000. Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord. Cell 102:363–375.
Loes, S., Kettunen, P., Kvinnsland, I. H., Taniguchi, M., Fujisawa, H., and Luukko, K. 2001. Expression of class 3 semaphorins and neuropilins receptors in the developing mouse tooth. Mech. Dev. 101:191–194.
Tse, C., Xiang, R. H., Bracht, T., and Naylor, S. L. 2002. Human semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res. 62:542–546.
Kuroki, T., Trapasso, F., Yendamuri, S., Matsuyama, A., Alder, H., Williams, N. N., Kaiser, L. R., Croce, C. M. 2003. Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer. Cancer Res. 63:3352–3355.
Koppel, A. M., Feiner, L., Kobayashi, H., and Raper, J. A. 1997. A 70 amino acid region within the semaphorin domain activates specific cellular response of semaphorin family members. Neuron 19:531–537.
Bagnard, D., Lohrum, M., Uziel, D., Puschel, A. W., Bolz, J., Chen, H., He, Z., Bagri, A., and Tessier Lavigne, M. 1998. Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections. Development 125:5043–5053.
Miyazaki, N., Furayama, T., Amasaki, M., Suigimoto, H., Sakai, T., Takeda, N., Kubo, T., and Inagaki, S. 1999. Mouse semaphorin H inhibits neurite outgrowth from sensory neurons. Neurosci. Res. 33:269–274.
Miyazaki, N., Furayama, T., Sakai, T., Fujioka, T., Mor, T., Ohaka, Y., Takeda, N., Kubo, T., and Inagaki, S. 1999. Developmental localization of semaphorin H messenger RNA acting as a collapsing factor on sensory axons in the mouse brain. Neuroscience 93:401–408.
Pozas, E., Pascual, M., Ba-Charvet, K. T., Guijarro, P., Sotelo, C., Chedotal, A., Del Rio, J. A., and Soriano, E. 2001. Age-dependent effects of secreted semaphorins 3A, 3F, and 3E on developing hippocampal axons: in vitro effects and phenotype of semaphorin 3A (-;/-;) mice. Mol. Cell. Neurosci. 18:26–43.
De Winter, F., Oudega, M., Lankhorst, A. J., Hamers, F. P., Blits, B., Ruitenberg, M. J., Pasterkamp, R. J., Gispen, W. H., and Verhaagen, J. 2002. Injury-induced class 3 semaphorin expression in the rat spinal cord. Exp. Neurol. 175:61–75.
Pasterkamp, R.J., De Winter, F., Holtmaat, A.J., and Verhaagen, J. 1998 Evidence for a role of the chemorepellent semaphorin III and its receptor neuropilin-1 in the regeneration of primary olfactory axons. J. Neurosci. 18:9962–9976.
De Castro, F, Hu, L., Drabkin, H., Sotelo, C., and Chédotal, A. 1999. Chemoattraction and chemorepulsion of olfactory bulb axons by different secreted semaphorins. J Neurosci. 19:4428–4436.
Renzi, M. J., Wexler, T. L., and Raper, J. A. 2000. Olfactory sensory axons expressing a dominant-negative semaphorin receptor enter the CNS early and overshoot their target. Neuron 28:437–447.
Cloutier, J. F., Giger, R. J., Koentges, G., Dulac, C., Kolodkin, A. L., and Ginty, D. D. 2002. Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons. Neuron 33:877–892.
Ide, C. 1983. Schwann cell basal lamina and nerve regeneration. Brain Res. 288:61–75.
Scherer, S. S. and Easter, S. S., Jr. 1984. Degenerative and regenerative changes in the trochlear nerve of goldfish. J. Neurocytol. 13:519–565.
Brown, M. C. and Hardman, V. 1987. A reassessment of the accuracy of reinnervation by motor neurons following crushing or freezing of the sciatic or lumbar spinal nerves of rats. Brain 110:695–705.
Spassky, N., de Castro, F., Le Bras, B., Heydon, K., QueraudLeSaux, F., Bich-Gallego, E., Chedotal, A., Zale, B., and Thomas, J. L. 2002. Directional guidance of oligodendroglial migration by class 3 semaphorins and netrin-1. J. Neurosci. 22:5992–6004.
Tetzlaff, W. 1982. Tight junction contact events and temporary gap junctions in the sciatic nerve fibers of the chicken during Wallerian degeneration and subsequent regeneration. J. Neurocytol. 11:839–858.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ara, J., Bannerman, P., Hahn, A. et al. Modulation of Sciatic Nerve Expression of Class 3 Semaphorins by Nerve Injury. Neurochem Res 29, 1153–1159 (2004). https://doi.org/10.1023/B:NERE.0000023602.72354.82
Issue Date:
DOI: https://doi.org/10.1023/B:NERE.0000023602.72354.82