Details

Autor(en) / Beteiligte

• Farrugia, Marija
• Vassallo, Neville
• Cauchi, Ruben J.

Titel

Disruption of Survival Motor Neuron in Glia Impacts Survival but has no Effect on Neuromuscular Function in Drosophila

Ist Teil von

• Neuroscience, 2022-05, Vol.491, p.32-42

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2022

Quelle

ScienceDirect

Beschreibungen/Notizen

• •Loss of Smn function in glia during development reduces survival to adulthood.•Motoric ability or neuronal morphology is not affected by reduced Smn levels in glia.•Gain of ALS-linked gene function in glia induces motor behavior and survival defects.•Glia-specific gain of TDP-43 function causes NMJ defects and muscle atrophy.•Perturbation of snRNP assembly factors affect viability rather than motor function. Increasing evidence points to the involvement of cell types other than motor neurons in both amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), the predominant motor neuron disease in adults and infants, respectively. The contribution of glia to ALS pathophysiology is well documented. Studies have since focused on evaluating the contribution of glia in SMA. Here, we made use of the Drosophila model to ask whether the survival motor neuron (Smn) protein, the causative factor for SMA, is required selectively in glia. We show that the specific loss of Smn function in glia during development reduced survival to adulthood but did not affect motoric performance or neuromuscular junction (NMJ) morphology in flies. In contrast, gain rather than loss of ALS-linked TDP-43, FUS or C9orf72 function in glia induced significant defects in motor behaviour in addition to reduced survival. Furthermore, glia-specific gain of TDP-43 function caused both NMJ defects and muscle atrophy. Smn together with Gemins 2–8 and Unrip, form the Smn complex which is indispensable for the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). We show that glial-selective perturbation of Smn complex components or disruption of key snRNP biogenesis factors pICln and Tgs1, induce deleterious effects on adult fly viability but, similar to Smn reduction, had no negative effect on neuromuscular function. Our findings suggest that the role of Smn in snRNP biogenesis as part of the Smn complex is required in glia for the survival of the organism, underscoring the importance of glial cells in SMA disease formation.