Sreedharan J, Neukomm LJ, Brown RH Jr, Freeman MR. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Curr Biol. 2015 Jul 28. pii: S0960-9822(15)00739-3. PMID: 26234214.
From the abstract: "The RNA-processing protein TDP-43 is central to the pathogenesis of amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron (MN) disease [1-4]. TDP-43 is conserved in Drosophila ... We used a mosaic approach to study age-dependent MN loss in the adult fly leg where it is possible to resolve single motor axons, NMJs and active zones, and perform rapid forward genetic screens. We show that expression of TDP-43Q331K caused dying-back of NMJs and axons ... We report the identification of three genes that suppress TDP-43 toxicity ... In addition to delineating genetic factors that modify TDP-43 toxicity, these results establish the Drosophila adult leg as a valuable new tool for the in vivo study of adult MN phenotypes."