The Role of <em>Wallenda</em> in Inducing Autophagy to Regulate Neuronal Cell Body Responses in <em>Drosophila </em>Photoreceptor Cells

<p> In this thesis, I investigate the relationship between <i>Wallenda (wnd) MAP Kinase Kinase Kinase </i>signaling and the induction of autophagy within <i>Drosophila </i>photoreceptor cell bodies. <i>Wallenda </i>has been identified as a regulator of the <i>wnd-JNK </i>signaling pathway that regulates a neuron’s response to injury. Using the Gal4-UAS system, I expressed <i>wnd </i>and other genes of interest using the promoters for opsin proteins. The opsin promoters become active at ~75% pupal development which ensures expression within the adult, rather than during development<i>. </i>Overexpression of <i>wnd</i> in <i>Drosophila </i>photoreceptor cells<i> </i>induces degeneration of the rhabdomeres, the microvillar membrane of photoreceptor cells that houses the phototransduction machinery. Overexpression of <i>wnd </i>signaling also leads to an induction of autophagy, as evident through transmission electron microscopy and fluorescent microscopy analysis. The autophagy response within the cell body is not related to a previously observed phenotype of axonal sprouting at the photoreceptor cell synapses due to <i>wnd </i>overexpression.</p><p> I also investigated the role of <i>wnd </i>under wildtype conditions in <i>Drosophila </i>photoreceptor cells using two<i> </i>loss of function mutants, <i>wnd¹ </i>and <i>wndKD </i>(Collins et al 2006). <i>wnd </i>function is not required under wildtype conditions in photoreceptor cells. Loss of <i>wnd </i>function has some effect at eclosion on the maintenance of rhodopsin levels; however, the levels recover to nearly wildtype levels by three days of age. Loss of <i>wnd </i>function does not negatively impact the levels of three other key phototransduction proteins, Transient Receptor Potential (TRP), NinaC, or Retinophilin (RTP). Despite the effect on rhodopsin levels at eclosion, no histological defects are observed within the photoreceptor cell bodies or their synapses based on light level fluorescent microscopy analysis. A role of <i>wnd </i>in regulating <i>norpA </i>induced photoreceptor cell degeneration has also been identified. The loss of<i> </i>function mutant <i>wnd¹</i> suppresses norpA degeneration up to 9 days under constant light conditions. </p><p> In summary, overexpression of <i>wnd </i>induces rhabdomere degeneration and autophagy within <i>Drosophila </i>photoreceptor cells. The autophagic cell body response does not regulate the synaptic sprouting phenotype also observed due to <i>wnd </i>overexpression. <i>wnd </i>function is not required for photoreceptor cell maintenance under wildtype conditions. I have also identified a novel role of <i>wnd </i>in regulating the degeneration of the phototransduction mutant, norpA.</p>