Activity provided by the innervating motor axon, Agrin, an extracellular heparan proteoglycan produced by motor neurons, the LDLR family member Lrp4 and MuSK, a muscle-specific kinase are the key players in neuromuscular synapse formation. The critical events during synapse formation include Agrin/Lrp4-mediated activation of MuSK, concentration of MuSK at the synapse and tyrosine phosphorylation. Signal transduction events downstream of MuSK lead to pre-and postsynaptic differentiation. Our research focuses on the role of MuSK during neuromuscular synapse development. Several projects are designed to examine the different aspects of MuSK function and downstream signaling events.