During the innervation of mammalian muscles, neuromuscular (NM) synapses form at specific sites on muscle fibres. For years, it has been thought that ingrowing nerves determine these synaptic sites. However, on , Liu and colleagues challenge this `neurocentric' view by reporting that theγ-subunit of the acetylcholine receptor (AChR), which is expressed in embryonic muscle but is replaced after birth by the ϵ-subunit, plays an essential role in NM synaptic patterning. In wild-type mice, pre-patterned AChR clusters form on muscle cells early in NM synaptogenesis but their subsequent role in synapse development is unclear. The researchers show that deletion of the AChR γ-subunit gene delays the formation of these clusters, which are also more broadly distributed than normal. Furthermore,the presynaptic nerves in the γ-null mice contact a broader region of the muscle than those in wild-type mice. These results indicate that the AChRγ-subunit is required for the formation of pre-patterned AChR clusters,which, in turn, determine the pattern of NM synaptogenesis.
