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Figure 1 | Molecular Neurodegeneration

Figure 1

From: Drosophila melanogaster as a model organism for Alzheimer’s disease

Figure 1

Genetic tools in Drosophila. In Drosophila the UAS/Gal4 expression system has been used extensively to express endogenous and exogenous sequences in the tissue of interest [39]. This is implemented using two different lines. The so-called driver line contains a Gal4 coding sequence inserted downstream of a promoter of an endogenous Drosophila gene. Gal4 is a transcription factor originating from Saccharomyces cerevisiae[40]. It specifically binds to promoter elements termed upstream activating sequence (UAS), thus activating expression of the downstream target sequence [40, 41]. A collection of Gal4 driver lines which display a great variety of Gal4 expression in numerous tissues and organs is available to the public [42]. Frequently used are the glass multimer reporter (GMR) driver inducing retinal expression [43] and the elav driver inducing pan-neuronal expression [44]. After crossbreeding both, the Gal4 driver and the UAS line, the UAS target sequences will be expressed in a spatiotemporal manner (depending on the Gal4 driver used). EP-elements are randomly inserted in the fly genome and contain UAS sites. Depending on the orientation EP-elements might facilitate activation (same orientation) or inactivation (reverse orientation) of neighboring genes in a Gal4-dependent manner. There are various collections of EP strains available allowing misexpression of a large number of fly genes [45, 46]. So-called RNAi lines express short inverted repeat sequences under UAS control. The sequence of the inverted repeat corresponds to an endogenous gene. Gal4-dependent expression of the inverted repeat results in the formation short hairpin RNAs (shRNAs). The presence of shRNAs initiates a series of cellular mechanisms eventually resulting in silencing of the corresponding endogenous gene by RNA interference (RNAi) [47].

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