Is Reelin the Answer to Synapse Elimination at the Neuromuscular Junction?

The formation of mature neuronal circuits during development involves elimination of a large number of synapses by activity-dependent processes. A recent study suggests that synapse elimination at the neuromuscular junction is impaired in reeler mutant mice, which are lacking the extracellular matrix protein Reelin. In this process, Reelin acts through an unexpected, proteolytic mechanism that is independent of Disabled 1, a cytoplasmic factor that mediates Reelin signaling in the central nervous system. This Perspective discusses possible models for Reelin function in the framework of activity-dependent synapse elimination at the neuromuscular junction.