In humans, there is a strong correlation between sensitivity to substances of abuse and addiction risk. This differential tolerance to drugs has a strong genetic component. The identification of human genetic factors that alter drug tolerance has been a difficult task. For this reason and taking advantage of the fact that Drosophila responds similarly to humans to many drugs, and that genetically it has a high degree of homology (sharing at least 70% of genes known to be involved in human genetic diseases), we looked for genes in Drosophila that altered their nicotine sensitivity. We developed an instantaneous nicotine vaporization technique that exposed flies in a reproducible way. The amount of nicotine sufficient to “knock out” half of control flies for 30 minutes was determined and this parameter was defined as Half Recovery Time (HRT). Two fly lines, L4 and L70, whose HRT was significantly longer than control´s were identified. The L4 insertion is a loss of function allele of the transcriptional factor escargot (esg), whereas L70 insertion causes miss-expression of the microRNA cluster miR-310-311-312-313 (miR-310c). In this work, we demonstrate that esg loss of function induces nicotine sensitivity possibly by altering development of sensory organs and neurons in the medial section of the thoracoabdominal ganglion. The ectopic expression of the miR-310c also induces nicotine sensitivity by lowering Esg levels thus disrupting sensory organs and possibly to the modulation of other miR-310c targets.

Highlights Rpt2-RNAi expression impairs the 26S proteasome. Reduction of Rpt2 in the Drosophila eye induces necrosis. Rpt2 reduction causes specific dopaminergic cluster neurodegeneration. Loss of Rpt2 induce hyperactive motor activity and sleep reduction.

Synphilin-1 is a protein encoded by the human SNCAIP gene whose function has yet to be fully understood. However, it has been linked to familial Parkinson’s disease (PD). Synphilin-1 is a major component of the Lewy bodies found in neurons in the substantia nigra pars compacta of PD patients. Synphilin-1 expression in serotonergic and/or dopaminergic neurons of Drosophila melanogaster induces neurodegeneration, as well as motor and non-motor PD like symptoms. In this work, we examined the contribution of the serotonergic and dopaminergic circuits in the development of PD-like phenotypes. We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.

statement: The gene escargot regulates proboscis, maxillary palps and antennae development in Drosophila melanogaster through two different developmental pathways: one involving cell adhesion protein DE-cadherin and another through the signaling molecule decapentaplegic. AbstractIn insects, imaginal discs form the adult structures. Imaginal discs are formed by two epithelial layers, the lower disc proper columnar epithelium and the upper peripodial squamous epithelium (also known as peripodial membrane). During morphogenesis and metamorphosis there is a complex crosstalk between these two epithelia that defines the final size and form of the adult organs. In this work we found that in the antennal disc, the dosage of the transcriptional factor Escargot (Esg) regulates the extension of the peripodial epithelium. A reduction in Esg expands the peripodial domain at the expense of the antennal disc proper causing a distortion of the anteroposterior compartments resulting in malformations or duplications of antennae and maxillary palps. In the labial disc, a different morphogenetic pathway controls its development, and loss of esg produces a complete loss of the proboscis through a pathway that involves dpp.