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First published online 11 November 2008
doi: 10.1242/jcs.031047

Journal of Cell Science 121, 3901-3911 (2008)
Published by The Company of Biologists 2008
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Research Article

Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Felipe A. Court1,2,*, Thomas H. Gillingwater1,2, Shona Melrose2, Diane L. Sherman2, Kay N. Greenshields3, A. Jennifer Morton4, John B. Harris5, Hugh J. Willison3 and Richard R. Ribchester1,2,{ddagger}

1 Euan MacDonald Centre for Motor Neurone Disease Research, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK
2 Centre for Neuroscience Research, The University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK
3 Division of Clinical Neuroscience, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK
4 Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK
5 Institute of Neuroscience Faculty of Medical Sciences, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK

{ddagger} Author for correspondence (e-mail: richard.ribchester{at}ed.ac.uk)

Accepted 27 August 2008

Neuromuscular junctions (NMJs) are normally thought to comprise three major cell types: skeletal muscle fibres, motor neuron terminals and perisynaptic terminal Schwann cells. Here we studied a fourth population of junctional cells in mice and rats, revealed using a novel cytoskeletal antibody (2166). These cells lie outside the synaptic basal lamina but form caps over NMJs during postnatal development. NMJ-capping cells also bound rPH, HM-24, CD34 antibodies and cholera toxin B subunit. Bromodeoxyuridine incorporation indicated activation, proliferation and spread of NMJ-capping cells following denervation in adults, in advance of terminal Schwann cell sprouting. The NMJ-capping cell reaction coincided with expression of tenascin-C but was independent of this molecule because capping cells also dispersed after denervation in tenascin-C-null mutant mice. NMJ-capping cells also dispersed after local paralysis with botulinum toxin and in atrophic muscles of transgenic R6/2 mice. We conclude that NMJ-capping cells (proposed name `kranocytes') represent a neglected, canonical cellular constituent of neuromuscular junctions where they could play a permissive role in synaptic regeneration.

Key words: Neuromuscular junction, Motor endplate, Motor nerve terminal, Schwann cell, Kranocyte, CD34, Neuregulin, Tenascin






© The Company of Biologists Ltd 2008