FIGURE 2.

Loss of seven unreported fly orthologs, corresponding to eight genes, strongly rescued (G₄C₂)₃₀-mediated neurodegeneration in a c9ALS Drosophila model. (A) A scale of magnitude of degeneration in fly eyes expressing (G₄C₂)₃₀ scored from –4 to 2. The control flies (score 0), whose eyes expressing (G₄C₂)₃₀, exhibited eye degeneration, as indicated by necrotic patches, loss of ommatidia, depigmentation, and retinal collapse. The degree of eye degeneration rescue by RNAi of the gene of interest (goi) ranged from –4 to 2, where score –4 represented the strongest degree of rescue and score 2 stood for the highest degree of enhancement. (B) Number of genes whose loss gave rise to different degrees of modifications. Strong rescue stood for a score ≤ –3, moderate (mod.) rescue or enhance for a score ≤ –2 or ≥ 2, mild rescue or enhance for a score ≤ –1 or ≥ 1, and no effect for a score > –1 and < 1. For a gene with multiple fly orthologs, the score corresponding to the strongest modification of eye degeneration was used to represent the effect of suppressing the gene. (C) Fly eyes expressing (G₄C₂)₃₀ with RNAi against (from left to right) Shab (fly ortholog of KCNB2 and KCNS3), Octα2R (fly ortholog of ADRA2B), ERR (fly ortholog of NR3C1), AstC-R1 (fly ortholog of P2RY14), Pp2B-14D (fly ortholog of PPP3CB), Ptp69D (fly ortholog of PTPRC), and Eip78C (fly ortholog of RARA).