Figure 6.

Overexpression of hTDP-43 or hFUS/caz^P398L in Gem3 mutant flies causes early mobility defects, reduced muscle size and aberrant puparial structures. (A) Third instar larvae with muscle-specific Gem3^BART expression have a significant reduction in velocity compared to wild-type controls. This deficit was profoundly enhanced on overexpression of hTDP-43^WT, hFUS^WT or caz^P398L. A similar result was obtained on knockdown of Gaulos (Glos RNAi), which served as a positive control. In the absence of Gem3^BART, only overexpression of hTDP-43^WT or hFUS^WT was found to induce a decrease in larval mobility compared to wild-type animals. (B) Compared to the wild-type control, Gem3^BART larvae also show a significant reduction in muscle size that dramatically worsens on Glos knockdown or upon overexpression of hTDP-43^WT, hFUS^WT, or caz^P398L, all directed to muscle. In a wild-type background, muscle size was also found reduced in larvae with Glos knockdown or those overexpressing FUS/caz^P398L. (C) Sluggish larval behaviour leads to the formation of puparia that have a significantly higher axial ratio (defined as length/width) compared to the baseline offered by Gem3^BART larvae. In (A–C) data presented are the mean ± S.E.M. of at least 3 independent experiments, and n ≥ 15 per genotype. Equal number of male and female larvae were used in each assay. Significance as tested by the unpaired t-test is indicated by the exact p-value, shown either in blue (comparison to wild-type larvae) or black (comparison to Gem3^BART larvae).