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

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posted on 2016-06-22, 00:00 authored by Stephanie A. Freed

In this thesis, I investigate the relationship between Wallenda (wnd) MAP Kinase Kinase Kinase signaling and the induction of autophagy within Drosophila photoreceptor cell bodies. Wallenda has been identified as a regulator of the wnd-JNK signaling pathway that regulates a neuron’s response to injury. Using the Gal4-UAS system, I expressed wnd 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. Overexpression of wnd in Drosophila photoreceptor cells induces degeneration of the rhabdomeres, the microvillar membrane of photoreceptor cells that houses the phototransduction machinery. Overexpression of wnd 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 wnd overexpression.

I also investigated the role of wnd under wildtype conditions in Drosophila photoreceptor cells using two loss of function mutants, wnd¹ and wndKD (Collins et al 2006). wnd function is not required under wildtype conditions in photoreceptor cells. Loss of wnd 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 wnd 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 wnd in regulating norpA induced photoreceptor cell degeneration has also been identified. The loss of function mutant wnd¹ suppresses norpA degeneration up to 9 days under constant light conditions.

In summary, overexpression of wnd induces rhabdomere degeneration and autophagy within Drosophila photoreceptor cells. The autophagic cell body response does not regulate the synaptic sprouting phenotype also observed due to wnd overexpression. wnd function is not required for photoreceptor cell maintenance under wildtype conditions. I have also identified a novel role of wnd in regulating the degeneration of the phototransduction mutant, norpA.

History

Date Modified

2017-06-05

Research Director(s)

Joseph O`Tousa

Degree

  • Master of Science

Degree Level

  • Master's Thesis

Program Name

  • Biological Sciences

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