Selective vulnerability of Dopaminergic neurons revealed by Genome-wide analysis

In Figure 1, this is a graph depicting the average number of DA neurons in the PPL1 cluster for each wild-caught DGRP fly stocks. There is natural variability in the amount of neurons at day 21. Table 1 contains top-ranked associated genes harboring SNPS found from this variation of DA neurons in the DGRP stocks. We functionally validated these genes through RNAi-mediated knockdown and mutagenesis at day 3 and day 21 to investigate degeneration of DA neurons. Figures 2,3, and 4 show the PPL1, PPM1/2 and PPM3 DA neuron clusters. We see a significant loss of DA neurons specific to certain genes in the PPL1 (Tow, Plexus, Trf2, Kirre, Tweek and Sestrin) and PPM1/2 (Tow, CG42339, Megalin, Trf2, Kirre, Tweek, and Lim3) clusters. While there is no loss in the PPM3 cluster for any of the genes. In Figure 5, we also found that CG42339 and Sesn double mutants progressively lost PPL1 neurons at day 21. While CG42339 loses neurons in the PPM1/2 cluster as well. Figure 6 represents climbing assays that were performed for both the RNAi-mediated knockdown and the mutagenesis at day 3 and day 21. There are select locomotive declines in CG42339, Kirre, and Sesn double mutants. When Megalin, Plexus, Tweek, Sestrin and Lim3 were knocked down in DA neurons we found a significant progressive locomotor dysfunction. We plan on moving forward with certain genes to further investigate their involvement in DA neuron maintenance.