We are interested in the molecular and developmental processes that lead to the establishment and structural remodeling of synapses. How do axons find and recognize their targets? And how do neuronal growth cones induce the formation of complex synaptic terminals? The Drosophila neuromuscular junction (NMJ) is an ideal system for discovering genes with conserved synaptic functions, as it shares important chemical and structural features with excitatory synapses in the vertebrate brain. To search for regulators of synapse formation and structural reorganization, we conducted a large-scale mutagenesis screen of neuromuscular synapses. We find genes that regulate axonal growth, synaptic activity and precise apposition of synaptic membranes. We also identified genes that are essential for reorganization, maturation and maintenance of synapses. Currently, we are characterizing the roles of the axon guidance molecule Sidestep, a member of the immunoglobulin superfamily, which is expressed along the paths of motor axons. Side strongly attracts motor axons, as ectopic expression, e.g. on trachea, distracts them away from their destined pathways. Lack of Side similarly leads to permanent innervation errors that are maintained throughout larval stages. Miswiring is irreparable and cause substantial locomotion defects. Precise expression of axon guidance molecules is thus essential for the development of wild-type locomotion patterns. Mutations in similar guidance molecules could therefore be involved in heritable locomotion and posture defects in vertebrates.
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