Title: Cell-selective Modulation of the Drosophila Neuromuscular System by a Neuropeptide Corresponding Author: Running Title: Cell-specific Modulation in Drosophila Larvae

27 Neuropeptides can modulate physiological properties of neurons in a cell-specific 28 manner. The present work examines whether a neuropeptide can also modulate muscle tissue in a 29 cell-specific manner, using identified muscle cells in third instar larvae of fruit flies. 30 DPKQDFMRFa, a modulatory peptide in the fruit fly Drosophila melanogaster, has been shown 31 to enhance transmitter release from motor neurons and to elicit contractions by a direct effect on 32 muscle cells. We report that DPKQDFMRFa causes a nifedipine-sensitive drop in input 33 resistance in some muscle cells (6 and 7) but not others (12 and 13). The peptide also increased 34 the amplitude of nerve-evoked contractions and compound excitatory junctional potentials 35 (EJPs) to a greater degree in muscle cells 6 and 7 than 12 and 13. Knocking down FMRFa 36 receptor (FR) expression separately in nerve and muscle indicate that both presynaptic and 37 postsynaptic FR expression contributed to the enhanced contractions, but EJP enhancement was 38 due mainly to presynaptic expression. Muscle-ablation showed that DPKQDFMRFa induced 39 contractions and enhanced nerve-evoked contractions more strongly in muscle cells 6 and 7 than 40 cells 12 and 13. In situ hybridization indicated that FR expression was significantly greater in 41 muscle cells 6 and 7 than 12 and 13. Taken together, these results indicate that DPKQDFMRFa 42 can elicit cell-selective effects on muscle fibres. The ability of neuropeptides to work in a cell43 selective manner on neurons and muscle cells may help explain why so many peptides are 44 encoded in invertebrate and vertebrate genomes. 45