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The role of fu2 gene in cell competition in Drosophila melanogaster
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Cell competition is a process by which less adapted cells (loser cells) are eliminated by surrounding, more competitive cells (winner cells). This homeostatic mechanism potentiates the correct animal development and ensures overall fitness of animal tissues.
In Drosophila melanogaster, cells display information about their fitness state via different spliced isoforms of the transmembrane protein Flower (Fwe). Suboptimal epithelial cells are detected and eliminated by apoptosis because they express FweLose isoforms, whereas more vigorous cells express Fweubi isoform, the winner isoform. Fwe code is, thus, a fitness indicator that allows direct cell competition and the discrimination between winner and loser cells. In addition to the Fwe code, Moreno’s team also identified early upregulated genes in loser cells that are outcompeted by dMyc-overexpressing winner cells, which behave as supercompetitors. One of these genes is fu2 which encodes a nuclear factor with Zinc-finger domains.
The goal of the project is to determine if fu2 is required for cell elimination in different cell competition contexts. To do so, molecular tools and transgenic flies were generated to assess the requirement of fu2 for loser cell elimination in contexts such as in Alzheimer’s disease and during the neuronal culling process.
Regarding the Alzheimer’s disease context, the results were inconclusive, as different lines of RNAi used to downregulate the expression of fu2 gave different results. Additionally, in the neuronal culling context, it was not possible to analyze the function of fu2, since the loss of the fitness marker azot (azot KO) did not show an expected reduction in cell death when compared with a wild-type retina (w1118). Finally, it was shown that fu2 knockout flies are homozygous viable.
The generation of new tools during this work will allow to clarify the results obtained and to evaluate the role of fu2 in Alzheimer’s disease, during normal retina development (neuronal culling) and in other cell competition (fwe-dependent events) contexts.
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Cell competition fu2 molecular tools Alzheimer’s disease neuronal culling