The objective of this Master thesis is to identify RNA interference (RNAi) and/or CRISPR/Cas9-
mediated sgRNAs that can phenocopy the loss of the presynaptic neurotransmitter-release
genes rop, syx1a, and snap25, resulting in the degeneration of wing sensory neurons in
Drosophila. In mice, deficiencies in mStxbp1, Stx1A, and Snap25 result in rapid
neurodegeneration, while deficiencies in Munc13 and Vamp2 do not affect neuronal viability.
Similarly, in Drosophila, neurons lacking either mStxbp1/rop or Stx1A/syx1a degenerate within
approximately 2-3 days, while neurons lacking Vamp2/nsyb remain morphologically intact
(Christel Schäfer, unpublished). Seven different RNAi or sgRNA lines targeting these five
presynaptic genes were assessed for their respective capacities to induce neurodegeneration
in GFP-labeled wing sensory neuron clones. Certain RNAi and sgRNAs lines targeting
mStxbp1/rop, Stx1A/syx1a, and Snap25/snap25 genes were able to partially phenocopy, to a
greater or lesser extent, the effect of these genes on neuronal viability. These results
demonstrate the potential of the tools for future investigations. These findings allow using some
of these tools in future studies to better dissect the impact of these gene mutations, particularly
on their function.