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.