Interactions between nerve and muscle: synapse elimination at the developing neuromuscular junction

Studies of synaptogenesis at the developing neuromuscular junction have provided a wealth of information regarding the various mechanisms that are involved in the formation of synaptic connections. In addition to synapse formation, however, the mature pattern of innervation at the neuromuscular junction (and elsewhere in the nervous system) depends on a significant loss of synaptic connections during development. The molecular mechanisms involved in the process of synapse elimination are not understood. Recent work at the neuromuscular junction suggests that changes in the postsynaptic cell may be necessary in order for nerve terminals to be eliminated. Thus, in contrast to synapse formation in which an axon terminal initiates a cascade of changes leading to the formation of pre- and postsynaptic specializations, synapse elimination may be initiated by local changes in the postsynaptic cell that disassemble the postsynaptic apparatus and ultimately remove the overlying terminal. In this review, we wish to examine the potential role that some of the factors involved in synapse formation might play in the less-well-understood phenomenon of synapse elimination.