Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences
Molecular and Cellular Neuroscience
Genetic studies of Wallerian degeneration have led to the identification of signaling molecules (e.g., dSarm/Sarm1, Axundead, and Highwire) that function locally in axons to drive degeneration. Here we identify a role for the Drosophila C2H2 zinc finger transcription factor Pebbled [Peb, Ras-responsive element binding protein 1 (RREB1) in mammals] in axon death. Loss of Peb in Drosophila glutamatergic sensory neurons results in either complete preservation of severed axons, or an axon death phenotype where axons fragment into large, continuous segments, rather than completely disintegrate. Peb is expressed in developing and mature sensory neurons, suggesting it is required to establish or maintain their competence to undergo axon death. peb mutant phenotypes can be rescued by human RREB1, and they exhibit dominant genetic interactions with dsarm mutants, linking peb/RREB1 to the axon death signaling cascade. Surprisingly, Peb is only able to fully block axon death signaling in glutamatergic, but not cholinergic sensory neurons, arguing for genetic diversity in axon death signaling programs in different neuronal subtypes. Our findings identify a transcription factor that regulates axon death signaling, and peb mutant phenotypes of partial fragmentation reveal a genetically accessible step in axon death signaling.
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Copyright the authors. Published under the PNAS license.
DOI of Published Version
Proc Natl Acad Sci U S A. 2018 Jan 2. pii: 201715837. doi: 10.1073/pnas.1715837115. [Epub ahead of print] Link to article on publisher's website
Wallerian degeneration, axons, axon death
Proceedings of the National Academy of Sciences of the United States of America
Farley, Jonathan E.; Burdett, Thomas C.; Barria, Romina; Neukomm, Lukas J.; Kenna, Kevin P.; Landers, John E.; and Freeman, Marc R., "Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration" (2018). GSBS Student Publications. 2053.