A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster

Abstract

Neurodegeneration arising from aging, injury or disease has devastating health consequences. Whereas neuronal survival and axon degeneration have been studied extensively, much less is known about how neurodegeneration impacts dendrites. To develop an assay for dendrite degeneration and repair in the Drosophila peripheral nervous system, we used photo-switchable caspase-3 (caspase-LOV) to induce neuronal damage with tunable severity by adjusting illumination duration, thereby revealing cell type-specific responses to caspase-3 induced dendrite degeneration in dendrite arborization (da) neurons. To ask whether mechanisms underlying axon degeneration also govern dendrite degeneration, we tested the involvement of the Wallerian degeneration pathway by examining the effects of expressing the mouse Wallerian degeneration slow (WldS) protein and knockdown of the Drosophila sterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein (dSarm1) and Axundead (Axed) in class 4 da neurons. Here we report WldS expression or knockdown of dSarm1 improved dendrite repair following caspase-3 induced dendrite degeneration. Whereas both dSarm1 and Axed were required for thermal nocifensive behavior in uninjured animals, WldS expression improved the recovery of thermal nocifensive behavior that was impaired by chronic low-level of caspase-LOV activity. By establishing ways to induce graded dendrite degeneration, we uncover a protective role of WldS in caspase-3 induced dendrite degeneration and repair.