Titre
Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration.
Type
article
Institution
Externe
Auteur(s)
Farley, J.E.
Auteure/Auteur
Burdett, T.C.
Auteure/Auteur
Barria, R.
Auteure/Auteur
Neukomm, L.J.
Auteure/Auteur
Kenna, K.P.
Auteure/Auteur
Landers, J.E.
Auteure/Auteur
Freeman, M.R.
Auteure/Auteur
Liens vers les personnes
ISSN
1091-6490
Statut éditorial
Publié
Date de publication
2018-02-06
Volume
115
Numéro
6
Première page
1358
Dernière page/numéro d’article
1363
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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 C <sub>2</sub> H <sub>2</sub> 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.
Sujets
PID Serval
serval:BIB_3D569E691EDA
PMID
Open Access
Oui
Date de création
2019-02-07T09:20:29.749Z
Date de création dans IRIS
2025-05-20T18:55:46Z