Fig. 1

Dsor1 (dMEK) modifies TDP-43-induced cytotoxicity in the in vivo Drosophila models. a-c’ TDP-43-induced eye degeneration (by GMR-Gal4) is suppressed by transgenic RNAi (#28,685) KD of Dsor1. UAS-lacZ (lacZ) and RNAi-Luciferase (RNAi-Luc) flies are used as the control for UAS-hTDP-43 and RNAi-Dsor1, respectively. d The degeneration scores in (a-c’) are quantified and shown as the violin plots with mean. e qPCR analysis confirming the KD of Dsor1 by RNAi-Dsor1. The relative mRNA levels of Dsor1 are normalized to actin and shown as percentage relative to that of the control flies (GMR > RNAi-Luc), which is set to 100%. Note that the Dsor1 mRNA levels are not fully decreased because the RNAi-Dsor1 transgene is expressed in the fly eye only (with GMR-Gal4), while the mRNA levels are examined in the homogenates of the entire fly head that includes many other cells expressing Dsor1 but not RNAi-Dsor1. f Adult-onset neuronal downregulation of Dsor1 (by elavGS) suppresses TDP-43-induced, age-dependent climbing decline. g The log-rank analysis of the survival curves shows that KD of Dsor1 in adult fly neurons extends the shortened lifespan of the elavGS > hTDP-43 flies. The number (n) of flies tested in each group is as indicated; the median lifespan is shown as mean ± SEM and the statistical significance is determined by one-way ANOVA. h Summary of the effect of downregulating the fly genes encoding the kinases in the three MAPK families on TDP-43-induced eye degeneration. Mean ± SEM; n = 10 eyes/group in (d), n = 3 in (e), n =  ~ 10 vials/group with ~ 20 flies each vial in (f). One-way ANOVA in (d, f) and Student’s t-test in (e). *p < 0.05, **p < 0.01, ***p < 0.001; ns, no significance. Scale bar: 100 μm. See Table S1 for the exact genotypes in each of the fly assays