The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis

Di Giaimo, Rossella; Durovic, Tamara; Barquin, Pablo; Kociaj, Anita; Lepko, Tjasa; Aschenbroich, Sven; Breunig, Christopher T.; Irmler, Martin; Cernilogar, Filippo M.; Schotta, Gunnar; Barbosa, Joana S.; Trümbach, Dietrich; Baumgart, Emily Violette; Neuner, Andrea M.; Beckers, Johannes; Wurst, Wolfgang; Stricker, Stefan H. und Ninkovic, Jovica (2018): The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis. In: Cell Reports, Bd. 25, Nr. 12: S. 3241-3251

Abstract

Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis. We identify the aryl hydrocarbon receptor (AhR) as a regulator of ependymoglia differentiation toward post-mitotic neurons. In vivo imaging shows that high AhR signaling promotes the direct conversionof a specific subset of ependymoglia into post-mitotic neurons, while low AhR signaling promotes ependymoglial proliferation. Interestingly, we observe the inactivation of AhR signaling shortly after injury followed by a return to the basal levels 7 days post injury. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Taken together, we identify AhR signaling as a crucial regulator of restorative neurogenesis timing in the zebrafish brain.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Fakultätsübergreifende Einrichtungen: Center for Integrated Protein Science Munich (CIPSM)
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2211-1247
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198