Schwann cells participate in synapse elimination at the developing neuromuscular junction

During the initial stages of innervation of developing skeletal muscles, the terminal branches of axons from multiple motor neurons form neuromuscular junctions (NMJs) on a small region of each muscle fiber, the motor endplate. Subsequently, the number of axonal inputs at the endplate region is reduced so that, at maturity, each muscle fiber is innervated by the terminals of a single motor neuron. The Schwann cells associated with the axon terminals are involved in the removal of these synapses but do not select the axon that is ultimately retained on each fiber. Schwann cells perform this function by disconnecting terminal branches from the myofiber surface and by attacking them phagocytically. Here we discuss how this behavior is regulated and argue that such regulation is not unique to development of neuromuscular innervation but is also expressed in the response of the mature NMJ to various manipulations and pathologies.