Neurobiology; Freeman Lab
First Thesis Advisor
Marc Freeman, PhD
axons, axon death, axon degeneration, Wallerian degeneration
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.
Farley, JE. The Transcription Factor Pebbled/RREB1 Regulates Injury-Induced Axon Degeneration. (2017). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 932. DOI: 10.13028/M2SH5B. https://escholarship.umassmed.edu/gsbs_diss/932
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