Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration
Authors
Farley, Jonathan E.Burdett, Thomas C.
Barria, Romina
Neukomm, Lukas J.
Kenna, Kevin P.
Landers, John E.
Freeman, Marc R.
Student Authors
Jonathan E. FarleyThomas C. Burdett
Academic Program
NeuroscienceDocument Type
Journal ArticlePublication Date
2018-01-02
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1073/pnas.1715837115Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33529PubMed ID
29295933Related Resources
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Copyright the authors. Published under the PNAS license.ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1715837115