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A Schwann cell mitogen accompanying regeneration of motor neurons

Nature volume 390, pages 614–618 (1997)Cite this article

Abstract

Motor neurons are the only adult mammalian neurons of the central nervous system to regenerate following injury1. This ability is dependent on the environment of the peripheral nerve and an intrinsic capacity of motor neurons for regrowth2. We report here the identification, using a technique known as messenger RNA differential display3, of an extracellular signalling molecule, previously described as the pancreatic secreted protein Reg-2 (ref. 4), that is expressed solely in regenerating and developing rat motor and sensory neurons. Axon-stimulated Schwann cell proliferation is necessary for successful regeneration5,6, and we show that Reg-2 is a potent Schwann cell mitogen in vitro. In vivo, Reg-2 protein is transported along regrowing axons and inhibition of Reg-2 signalling significantly retards the regeneration of Reg-2-containing axons. During development, Reg-2 production by motor and sensory neurons is regulated by contact with peripheral targets. Strong candidates for peripheral factors regulating Reg-2 production are cytokines of the LIF/CNTF family, because Reg-2 is not expressed in developing motor or sensory neurons of mice carrying a targeted disruption of the LIF receptor gene, a common component of the receptor complexes for all of the LIF/CNTF family7.

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Figure 1: Identification of Reg-2 as a gene expressed in regenerating motor and sensory neurons.
Figure 2: Reg-2 protein localization in regenerating motor neurons.
Figure 3: In vivo inhibition of Reg-2 retards regeneration.
Figure 4: Reg-2 is a Schwann-cell mitogen in vitro.
Figure 5: Reg-2 expression in developing neurons is regulated by peripherally derived neurotrophic factors.

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Acknowledgements

We thank N. Unwin and M. Goedert for critical comments on the manuscript, and H. McMahon and A. Randall for technical advice.

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Author notes

  1. Frederick J. Livesey

    Present address: Department of Zoology, Trinity College, Dublin, 2, Ireland

  2. Frederick J. Livesey: Correspondence and requests for materials should be addressed to F.J.L.

Authors and Affiliations

  1. MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK

    Frederick J. Livesey, John A. O'Brien & Stephen P. Hunt

  2. Centre for Genome Research, University of Edinburgh, EH9 3JQ, Edinburgh, UK

    Meng Li & Austin G. Smith

  3. Departments of Internal Medicine and Physiology, University of Manitoba, R3E 3J7, Winnipeg, Canada

    Liam J. Murphy

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Correspondence to Frederick J. Livesey.

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Livesey, F., O'Brien, J., Li, M. et al. A Schwann cell mitogen accompanying regeneration of motor neurons. Nature 390, 614–618 (1997). https://doi.org/10.1038/37615

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