GSBS Dissertations and Theses

ORCID ID

0000-0003-3163-5570

Approval Date

12-11-2017

Document Type

Doctoral Dissertation

Academic Program

Neuroscience

Department

Neurobiology; Freeman Lab

First Thesis Advisor

Marc Freeman, PhD

Keywords

axons, axon death, axon degeneration, Wallerian degeneration

Abstract

Neurons establish complex networks within the nervous system allowing for rapid cell-cell communication via their long, thin axonal processes. These wire-thin projections are susceptible to a number of insults or injuries, and axonal damage can lead to disruption in signal propagation and an overall dysfunction of the neural network. Recent research focused on investigating the underlying mechanisms of injury-induced axon degeneration led to the discovery of a number of endogenous, pro-degenerative molecules such as dSarm/Sarm1, Highwire/Phr1, and Axundead. These signaling molecules are thought to execute axon degeneration in response to injury locally within the distal severed axon, but the exact mechanism of action is unclear.

To further identify novel participants of the axon death signaling cascade, we performed an unbiased forward genetic mutagenesis screen using the sensory neurons within the adult wing of Drosophila melanogaster. We identified a novel role for the C2H2 zinc finger transcription factor, Pebbled (Peb)/Ras-responsive element binding protein 1 (RREB1) in partially suppressing injury-induced axon degeneration. Loss of function peb mutant glutamatergic neurons present two distinct axon degeneration defects: either complete protection from axotomy, or they exhibit a novel phenotype in which axons fragment into long, continuous pieces instead of undergoing complete degeneration. Additionally, we show an enhancement of the peb protective phenotype when dSarm levels are decreased, but not with reduced levels of axundead. These data provide the first evidence of a transcription factor involved in regulating injury-induced axon degeneration signaling in vivo.

DOI

10.13028/M2SH5B

Rights and Permissions

Licensed under a Creative Commons license

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.