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

By Rossella Di Giaimo, Tamara Durovic, Pablo Barquin, Anita Kociaj, Tjasa Lepko, Sven Aschenbroich, Christopher T. Breunig, Martin Irmler, Filippo M. Cernilogar, Gunnar Schotta, Joana S. Barbosa, Dietrich Trümbach, Emily Violette Baumgart, Andrea M. Neuner, Johannes Beckers, Wolfgang Wurst, Stefan H. Stricker and Jovica Ninkovic

Abstract

Summary: 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 conversion of 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. : Zebrafish have a high capacity to replace lost neurons after brain injury. Di Giaimo et al. identify the aryl hydrocarbon receptor (AhR) as a crucial regulator of restorative neurogenesis timing in the zebrafish brain. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Keywords: neurogenesis, regeneration, aryl hydrocarbon receptor, direct conversion, zebrafish, live imagin

Topics: Biology (General), QH301-705.5
Publisher: Elsevier
Year: 2018
DOI identifier: 10.1016/j.celrep.2018.11.055
OAI identifier: oai:doaj.org/article:df6711126cc642e2a628a30c50cc9aaa
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