Tau and tau reporters disrupt central projections of sensory neurons in Drosophila.
In this paper, the authors report that the expression of tau-based reporter genes causes severe defects in the morphology of sensory neurons in adult Drosophila. Targeted expression of tau-green fluorescent protein (tau-GFP) in sensory neurons, using the galactosidase-4 (GAL4) system, produced a range of characteristic defects in expressing neurons. The defects observed included loss of axons, abnormal axon bundling, reduced sensory arborisations, and axonal swellings (beads). Blind comparisons of adult sensory neurons labelled with tau-GFP or CD8-GFP showed that tau-GFP neurons exhibited many more defects than CD8-GFP-expressing neurons. CD8-GFP was found to induce no significant defects on sensory neuron morphology. Expression of tau-lacZ and human tau in sensory neurons produced defects comparable to those seen with tau-GFP. A developmental study showed that tau-expressing axons grow normally and innervate the correct regions of the neuropil. The absence of these axons later in development suggests that tau-expressing axons are lost after initial ingrowth. Examination of silver-stained sections suggests that the absence of axons is due to axon loss rather than failure of the expression system to label the neurons. The results suggest that the expression of tau-based reporter constructs causes severe defects in sensory neurons, resulting in degeneration. The results also indicate that Drosophila may provide a useful model system for examining the role of tau in neurodegenerative disorders.
Williams
D W
DW
School of Biological Sciences, University of Southampton, Southampton SO16 7PX, United Kingdom.
Tyrer
M
M
Shepherd
D
D
D000344:Afferent Pathways / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D004330:Drosophila / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017930:Genes, Reporter / Q000502:physiology*; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000494:pharmacology; D007866:Leg / Q000294:innervation / Q000473:pathology / Q000502:physiology; D008164:Luminescent Proteins / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D016875:tau Proteins; D049452:Green Fluorescent Proteins