A study of the molecular mechanism of selective synapse formation using Drosophila as a model system

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The aim of this research was to elucidate the molecular mechanism of selective synapse formation by using the Drosophila neuromuscular connectivity as a model system. For this end, we adopted misexpression screening to search for genes whose ectopic expression in all muscles alters neuromuscular specificity.Approximately 500 independent UAS-insertion lines (GS lines, Toba et al., Genetics, 1999) were crossed to 24B-GAL4 line and F1 third instar larvae were screened for non-autonomous phenotypes in motor nerve projection. While some of the lines showed cell autonomous phenotypes in which muscle differentiation is apparently impaired, several displayed specific defects in the guidance and/or synaptogenesis of motor nerves. Responsible transcripts for the latter phenotypes were then cloned by RT-PCR and were sequenced. Two of the lines were found to be in the netrin B and capricious genes, which had been previously shown to function as axon guidance cues in this system, thus indicating the effectiveness of our screening.By characterizing the remaining lines, we succeeded in identifying a novel expression was induced in all muscles, motoneurons that normally innervate muscle 12 formed ectopic synapses on a neighboring muscle 13. The target specificity of these motoneurons was also altered in the loss-of-function mutant of fend. During embryonic development, fend mRNA was detected in a subset of cells in the central nervoussystem and in the periphery. These results suggest that FEND is a novel axon guidance molecule involved in neuromuscular specificity.