Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions.
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.
Court
Felipe A
FA
Euan MacDonald Centre for Motor Neurone Disease Research, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
Gillingwater
Thomas H
TH
Melrose
Shona
S
Sherman
Diane L
DL
Greenshields
Kay N
KN
Morton
A Jennifer
AJ
Harris
John B
JB
Willison
Hugh J
HJ
Ribchester
Richard R
RR
D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000648:ultrastructure; D049109:Cell Proliferation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000378:metabolism; D009469:Neuromuscular Junction / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure