The Power and Richness of Modelling Tauopathies in Drosophila

Abstract

Tauopathies are a group of neurodegenerative disorders characterised by altered levels of phosphorylation or mutations in the neuronal microtubule protein Tau. The heterogeneous pathology of tauopathies suggests differential susceptibility of different neuronal types to wild-type and mutant Tau. The genetic power and facility of the Drosophila model has been instrumental in exploring the molecular aetiologies of tauopathies, identifying additional proteins likely contributing to neuronal dysfunction and toxicity and novel Tau phosphorylations mediating them. Importantly, recent results indicate tissue- and temporal-specific effects on dysfunction and toxicity coupled with differential effects of distinct Tau isoforms within them. Therefore, they reveal an unexpected richness of the Drosophila model that, coupled with its molecular genetic power, will likely play a significant role in our understanding of multiple tauopathies potentially leading to their differential treatment.

Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau

“…Next, we asked whether miR-219 influences tau toxicity in vivo. Transgenic Drosophila that express human tau are useful for modeling fundamental mechanisms of tau biology and tauopathy (13). Furthermore, many cellular mechanisms are conserved between Drosophila and humans, including miRNA regulation (14).…”

Modelling Tauopathies in Drosophila: Insights from the Fruit Fly

“…Numerous models of tauopathy, in both vertebrates [8, 9] and invertebrates [10, 11], have been generated to address links between tau biology and pathology. Drosophila occupies a unique position amongst model organisms because of the rich history of its use as a genetic model and hence its powerful genetic tractability.…”

“…Kosmidis et al, (2010) have shown that whilst the expression of human wild-type 0N4R tau and 2N4R tau caused a severe ablation of mushroom bodies in adult fly brains, the expression of human wild type 0N3R tau, bovine tau, and Drosophila tau have no effect [59]. Interestingly however, despite this lack of effect on the integrity of mushroom bodies, the expression of bovine and Drosophila tau leads to learning and memory impairments [10, 51, 65]. This clearly shows a strong isoform specific effect—some isoforms are directly toxic; others cause profound dysfunction rather than overt neurotoxicity.…”

In vivo magnetic resonance microscopy of Drosophilae at 9.4 T

“…This result allows us to consider using MRI to detect degeneration in other pathologies. Drosophila is now a well-established model of human neurodegenerative diseases such as tauopathies, spinocerebellar ataxias (Machado-Joseph disease), Parkinson's or Alzheimer's diseases [49][50][51]. The advantages of drosophila as a model system are numerous; in particular, drosophila allows enhancer/suppressor screens and a great number of mutants are available [52,53].…”