Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions.

We have studied the spatial deployment of synapses arising from different axons that converge on the same developing neuromuscular junctions. Labeling the competing synaptic "cartels" with different dyes in mouse muscle showed that, perinatally, each axon adds similar terminal areas, whereas later, areas occupied by the competing cartels diverged by gradual elimination of one axon's synapses and ongoing addition of synaptic area by the other. Activity-dependent labeling of synapses capable of vesicle recycling in snake muscle also revealed a gradual change in territories occupied by competing inputs, implying that an axon maintained some functional synapses even as others in its cartel were being eliminated. Thus the process of synapse elimination is gradual, with loss of one viable synapse after another, until an axon is left with no synaptic territory and withdraws.