Fig. 6: Fim alters neuronal phenotypes in the giant fibers in YARS1 and GARS1 neuropathy Drosophila models.

a Evaluation of the giant fiber-tergotrochanteral motoneuron connection (GF/TTMn; other connections omitted for simplicity) in the ventral nerve cord of adult flies. Sample traces of a train stimulation and GF/TTMn recordings in controls, severely impaired YARS1^CMT mutant (YARS1^{153-156delVKQV}-expressing) and animals with improved GF/TTMn function in Fim^Def background. b Quantification of the ability of the GF/TTMn synapse to follow repetitive stimuli in control, YARS1^WT and CMT mutant animals, in the background of endogenous-, increased- or decreased Fim expression; n = 24, 20, 12, 19, 18, 14, 30, 10, 15, 28, 19, and 20 (from left to right) giant fiber recordings from eight days-old female flies. **p < 0.01 and ***p < 0.001, one-way ANOVA with Bonferonni Multiple Comparison Test. c GF terminal morphology visualized by neurobiotin dye injection in YARS1^WT, YARS1^{153-156delVKQV}, and flies with improved GF/TTMn responses (Fim^Def; YARS1^{153-156delVKQV}). Yellow dashed line depicts constrictions at the axonal terminal in the mutant. Scale bar – 20 µm. d The same electrophysiological paradigm was used to evaluate the ability of the GF/TTMn synapse to follow repetitive stimuli in control, GARS^WT and GARS^CMT– expressing animals, by changing the expression levels of Fim; n = 24, 20, 12, 14, 10, 12, 18, 10, and 26 (from left to right) giant fiber recordings from 8-day-old female flies; *p = 0.0159 and ***p < 0.001, by a two-sided Mann-Whitney test. Controls are reused in graph b and d. Data in b and d presented as mean values ± SEM. e GF terminal morphology visualized with lucifer yellow GF dye-filing in CTRL, GARS1^CMT, and flies with improved GF/TTMn responses (Fim^Def; GARS1^CMT). Yellow dashed line depicts the thin, irregular axonal terminal that splits in two (yellow arrowheads) in the mutant. Scale bar – 50 µm. Source data are provided as a Source data file.