950A Poster - 15. Models of human disease
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Han-Hsuan Liu ¹; Chien-Hsiang Hsu ²; Lily Jan ¹; Yuh-Nung Jan ¹

Affiliations:
1) Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, United States.; 2) Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, United States.

Keywords:
a. neural degeneration; o. regeneration

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 in the Drosophila peripheral nervous system, we used photo-switchable caspase-3 (caspase-LOV) to induce neurodegeneration with tunable severity by adjusting illumination duration in class 4 dendrite arborization (c4da) neurons during development and adulthood. We found that c4da neurons were able to sustain mild caspase-3 induced neurodegeneration and continue to grow. 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 (Wld^S) protein in larval and adult c4da neurons. Here we report Wld^S expression protect c4da neurons from caspase-3 induced dendrite degeneration in larval and adult c4da neurons through reducing the dendrite elimination without affecting dendrite addition. At the functional lever, Wld^S 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 Wld^S in caspase-3 induced dendrite degeneration.