Genetic upregulation of an endogenous <i>Drosophila</i> chaperone reduces toxicity of TDP-43 and its disease associated fragment.

<p>A) Light and scanning electron microscope images demonstrating the effects of the TDP-43 and TDP-25 constructs when expression is driven by <i>gmr-GAL4</i>, in the presence and absence of co-expression of the chaperone CG14207. Light micrographs taken at 7.5× magnification, of fly eyes and inset are flies of the same genotype imaged using a scanning electron microscope at 200× magnification. Adjacent are low and high magnification confocal microscopy images of imaginal eye discs of third instar larvae. TDP-43 and TDP-25 distribution is shown by anti-HA (red) staining. TOTO-3 (blue) detects nuclei. White arrowheads indicate aggregates. White arrows indicate the location of the morphogenetic furrows and white boxes represent the areas shown at higher magnification. Low magnification scale bars = 100 µm and high magnification scale bars = 10 µm. B) Western blot detecting soluble (RIPA soluble) and insoluble (9 M urea soluble) fractions of TDP-43 and TDP-25 from fly brain homogenates in the presence or absence of the co-expression of CG14207, under reducing conditions. β-actin was used as a loading control. C) Western blot detecting soluble (RIPA soluble) fractions under non-reducing conditions, using an anti-HA antibody. β-actin was used as a loading control. D) Light microscope images demonstrating the effects of the TDP-25 construct when expression is driven by a different <i>gmr-GAL4</i> driver, which generates expression to a greater extent than that used previously, in the presence and absence of the co-expression of CG14207. Light micrographs of <i>Drosophila</i> eyes taken at 7× magnification.