The Journal of Cell Biology, Vol 129, 443-458, Copyright © 1995 by The Rockefeller University Press

ARTICLES

Transforming growth factor-beta 1 regulates axon/Schwann cell interactions

S Einheber, MJ Hannocks, CN Metz, DB Rifkin and JL Salzer
Department of Cell Biology, New York University Medical School, New York 10016, USA.

We have investigated the potential regulatory role of TGF-beta in the interactions of neurons and Schwann cells using an in vitro myelinating system. Purified populations of neurons and Schwann cells, grown alone or in coculture, secrete readily detectable levels of the three mammalian isoforms of TGF-beta; in each case, virtually all of the TGF- beta activity detected is latent. Expression of TGF-beta 1, a major isoform produced by Schwann cells, is specifically and significantly downregulated as a result of axon/Schwann cell interactions. Treatment of Schwann cells or Schwann cell/neuron cocultures with TGF-beta 1, in turn, has dramatic effects on proliferation and differentiation. In the case of purified Schwann cells, treatment with TGF-beta 1 increases their proliferation, and it promotes a pre- or nonmyelinating Schwann cell phenotype characterized by increased NCAM expression, decreased NGF receptor expression, inhibition of the forskolin-mediated induction of the myelin protein P0, and induction of the Schwann cell transcription factor suppressed cAMP-inducible POU protein. Addition of TGF-beta 1 to the cocultures inhibits many of the effects of the axon on Schwann cells, antagonizing the proliferation induced by contact with neurons, and, strikingly, blocking myelination. Ultrastructural analysis of the treated cultures confirmed the complete inhibition of myelination and revealed only rudimentary ensheathment of axons. Associated defects of the Schwann cell basal lamina and reduced expression of laminin were also detected. These effects of TGF-beta 1 on Schwann cell differentiation are likely to be direct effects on the Schwann cells themselves which express high levels of TGF-beta 1 receptors when cocultured with neurons. The regulated expression of TGF- beta 1 and its effects on Schwann cells suggest that it may be an important autocrine and paracrine mediator of neuron/Schwann cell interactions. During development, TGF-beta 1 could serve as an inhibitor of Schwann cell proliferation and myelination, whereas after peripheral nerve injury, it may promote the transition of Schwann cells to a proliferating, nonmyelinating phenotype, and thereby enhance the regenerative response.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Wang, H., Tewari, A., Einheber, S., Salzer, J. L., Melendez-Vasquez, C. V. (2008). Myosin II has distinct functions in PNS and CNS myelin sheath formation. JCB 182: 1171-1184 [Abstract] [Full Text]  
• Zhang, Y., Taveggia, C., Melendez-Vasquez, C., Einheber, S., Raine, C. S., Salzer, J. L., Brosnan, C. F., John, G. R. (2006). Interleukin-11 Potentiates Oligodendrocyte Survival and Maturation, and Myelin Formation.. J. Neurosci. 26: 12174-12185 [Abstract] [Full Text]  
• D'Antonio, M., Droggiti, A., Feltri, M. L., Roes, J., Wrabetz, L., Mirsky, R., Jessen, K. R. (2006). TGFbeta Type II Receptor Signaling Controls Schwann Cell Death and Proliferation in Developing Nerves.. J. Neurosci. 26: 8417-8427 [Abstract] [Full Text]  
• Atanasoski, S., Scherer, S. S., Sirkowski, E., Leone, D., Garratt, A. N., Birchmeier, C., Suter, U. (2006). ErbB2 Signaling in Schwann Cells Is Mostly Dispensable for Maintenance of Myelinated Peripheral Nerves and Proliferation of Adult Schwann Cells after Injury. J. Neurosci. 26: 2124-2131 [Abstract] [Full Text]  
• Hall, S. (2005). The response to injury in the peripheral nervous system. J Bone Joint Surg Br 87-B: 1309-1319 [Full Text]  
• Ogata, T., Iijima, S., Hoshikawa, S., Miura, T., Yamamoto, S.-i., Oda, H., Nakamura, K., Tanaka, S. (2004). Opposing Extracellular Signal-Regulated Kinase and Akt Pathways Control Schwann Cell Myelination. J. Neurosci. 24: 6724-6732 [Abstract] [Full Text]  
• Melendez-Vasquez, C. V., Einheber, S., Salzer, J. L. (2004). Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains. J. Neurosci. 24: 3953-3963 [Abstract] [Full Text]  
• Parkinson, D. B., Dong, Z., Bunting, H., Whitfield, J., Meier, C., Marie, H., Mirsky, R., Jessen, K. R. (2001). Transforming Growth Factor beta (TGFbeta ) Mediates Schwann Cell Death In Vitro and In Vivo: Examination of c-Jun Activation, Interactions with Survival Signals, and the Relationship of TGFbeta -Mediated Death to Schwann Cell Differentiation. J. Neurosci. 21: 8572-8585 [Abstract] [Full Text]  
• Sloan, A.J., Couble, M.-L., Bleicher, F., Magloire, H., Smith, A.J., Farges, J.-C. (2001). Expression of TGF-{beta} Receptors I and II in the Human Dental Pulp by in situ Hybridization. ADR 15: 63-67 [Abstract]  
• Zanazzi, G., Einheber, S., Westreich, R., Hannocks, M.-J., Bedell-Hogan, D., Marchionni, M. A., Salzer, J. L. (2001). Glial Growth Factor/Neuregulin Inhibits Schwann Cell Myelination and Induces Demyelination. JCB 152: 1289-1300 [Abstract] [Full Text]  
• Tikoo, R., Zanazzi, G., Shiffman, D., Salzer, J., Chao, M. V. (2000). Cell Cycle Control of Schwann Cell Proliferation: Role of Cyclin-Dependent Kinase-2. J. Neurosci. 20: 4627-4634 [Abstract] [Full Text]  
• Yang, L., Qiu, C. X., Ludlow, A., Ferguson, M. W. J., Brunner, G. (1999). Active Transforming Growth Factor-ß in Wound Repair : Determination Using a New Assay. Am. J. Pathol. 154: 105-111 [Abstract] [Full Text]  
• Creange, A., Belec, L., Clair, B., Degos, J.-D., Raphael, J.-C., Gherardi, R. K (1998). Circulating transforming growth factor beta 1 (TGF-beta 1) in Guillain-Barre syndrome: decreased concentrations in the early course and increase with motor function. J. Neurol. Neurosurg. Psychiatry 64: 162-165 [Abstract] [Full Text]  
• Gillen, C., Korfhage, C., Muller, H. W. (1997). {blacksquare} REVIEW : Gene Expression in Nerve Regeneration. Neuroscientist 3: 112-122 [Abstract]  
• Lisak, R. P (1996). In vitro studies of glial cells: what can we learn about demyelinating diseases?. Mult Scler 2: 173-178 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents