Sidestep-induced neuromuscular miswiring causes severe locomotion defects in larvae.

Mutations in motor axon guidance molecules cause aberrant projection patterns of motor nerves. As most studies in have analysed these molecules in fixed embryos, the consequences for larval locomotion are entirely unexplored Here, we took advantage of ()-mutant larvae that display severe locomotion defects because of irreparable innervation errors. Mutations in affected all motor nerve branches and all body wall regions. Innervation defects were non-stereotypical, showing unique innervation patterns in each hemisegment. Premature activation of Side in muscle precursors abrogated dorsal migration of motor nerves, resulting in larvae with a complete loss of neuromuscular junctions on dorsal-most muscles. High-speed videography showed that these larvae failed to maintain substrate contact and inappropriately raised both head and tail segments above the substrate, resulting in unique 'arching' and 'lifting' phenotypes. These results show that guidance errors in mutants are maintained throughout larval life and are asymmetrical with respect to the bilateral body axis. Together with similar findings in mice, this study also suggests that miswiring could be an underlying cause of inherited movement disorders.