Amyotrophic Lateral Sclerosis Genes in Drosophila melanogaster

Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disease characterized by the progressive degeneration of upper and lower motoneurons. Most ALS cases are sporadic but approximately 10% of ALS cases are due to inherited mutations in identified genes. ALS-causing mutations were identified in over 30 genes with superoxide dismutase-1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), fused in sarcoma (FUS), and TAR DNA-binding protein (TARDBP, encoding TDP-43) being the most frequent. In the last few decades, Drosophila melanogaster emerged as a versatile model for studying neurodegenerative diseases, including ALS. In this review, we describe the different Drosophila ALS models that have been successfully used to decipher the cellular and molecular pathways associated with SOD1, C9orf72, FUS, and TDP-43. The study of the known fruit fly orthologs of these ALS-related genes yielded significant insights into cellular mechanisms and physiological functions. Moreover, genetic screening in tissue-specific gain-of-function mutants that mimic ALS-associated phenotypes identified disease-modifying genes. Here, we propose a comprehensive review on the Drosophila research focused on four ALS-linked genes that has revealed novel pathogenic mechanisms and identified potential therapeutic targets for future therapy.

Tirant Stealthily Invaded Natural Drosophila melanogaster Populations during the Last Century

It was long thought that solely three different transposable elements (TEs)—the I-element, the P-element, and hobo—invaded natural Drosophila melanogaster populations within the last century. By sequencing the “living fossils” of Drosophila research, that is, D. melanogaster strains sampled from natural populations at different time points, we show that a fourth TE, Tirant, invaded D. melanogaster populations during the past century. Tirant likely spread in D. melanogaster populations around 1938, followed by the I-element, hobo, and, lastly, the P-element. In addition to the recent insertions of the canonical Tirant, D. melanogaster strains harbor degraded Tirant sequences in the heterochromatin which are likely due to an ancient invasion, likely predating the split of D. melanogaster and D. simulans. These degraded insertions produce distinct piRNAs that were unable to prevent the novel Tirant invasion. In contrast to the I-element, P-element, and hobo, we did not find that Tirant induces any hybrid dysgenesis symptoms. This absence of apparent phenotypic effects may explain the late discovery of the Tirant invasion. Recent Tirant insertions were found in all investigated natural populations. Populations from Tasmania carry distinct Tirant sequences, likely due to a founder effect. By investigating the TE composition of natural populations and strains sampled at different time points, insertion site polymorphisms, piRNAs, and phenotypic effects, we provide a comprehensive study of a natural TE invasion.

Drosophila melanogaster research: history, breakthrough and perspectives

The common fruit fly, or Drosophila Melanogaster, has been used as an object of biomedicals studies for over a century. It has been mostly employed in genetic research, as it exhibits several advantages which make its use relatively easy and cheap, with the results widely translatable into further vertebrate studies. This model been the basis of the work of Christiane Nusslein-Volhard, who together with Eric Wieschaus unravelled much of the mystery surrounding early drosophila development in the 1970s-1980s, laying foundations for broader understanding of multicellular organism embryogenesis, which brought them a Nobel prize in Physiology and Medicine in 1995. The knowledge gained from drosophila studies improves the basic understanding of developmental processes, while the model itself is relatively easy to maintain, analyse and translate the results onto other species. While models such as Zebrafish present better with other vertebrates, drosophila remains a very important element of genetic research, finding even more applications with the development of current science and medicine. Hence, in this short review, the outline of the history, breakthroughs and perspectives of the drosophila research has been presented.

Contradictory Results in Microbiome Science Exemplified by Recent Drosophila Research

ABSTRACT The bacterium Lactobacillus plantarum is prevalent in animal guts and is widely regarded as beneficial and probiotic. D. Fast et al. (mBio 9:e01114-18, 2018, https://doi.org/10.1128/mBio.01114-18) make the surprising discovery that L. plantarum reduces the life span of Drosophila melanogaster and link this effect with the loss and weakened proliferation of stem cells in the Drosophila gut. These results are apparently at odds with published evidence for beneficial effects of L. plantarum, especially promoting high developmental rates and stimulating stem cell proliferation in young Drosophila. The among-study discrepancies highlight the context dependence of many effects of gut microbes on host health, likely influenced by host age and genotype, variation among bacterial strains, and diet. The diversity of results offers an opportunity to elucidate a fundamental mechanism(s) and the circumstances that dictate whether gut bacteria have positive or negative effects on host health. These studies also reinforce the value of Drosophila as an emerging model system for probiotic science.