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Cell Rep. 2018 Dec 18;25(12):3241-3251.e5. doi: 10.1016/j.celrep.2018.11.055.

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

Author information

1
Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany; Department of Biology, University of Naples Federico II, 80134 Naples, Italy.
2
Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany; Graduate School of Systemic Neurosciences, Biomedical Center of LMU, 82152 Planegg, Germany.
3
Universidad Pablo de Olavide, Sevilla, 41013 Sevilla, Spain.
4
MCN Junior Research Group, Munich Center for Neurosciences, 82152 Munich, Germany; Epigenetic Engineering, Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany.
5
Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
6
Division of Molecular Biology, Biomedical Center, Faculty of Medicine, LMU Munich, 82152 Planegg, Germany.
7
Division of Molecular Biology, Biomedical Center, Faculty of Medicine, LMU Munich, 82152 Planegg, Germany; Munich Center for Integrated Protein Science (CiPSM), 82152 Planegg, Germany.
8
Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany.
9
Institute of Developmental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
10
Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany; Technische Universität München, Chair of Experimental Genetics, 85354 Freising-Weihenstephan, Germany.
11
Institute of Developmental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Munich Cluster for Systems Neurology SYNERGY, 82152 Planegg, Germany; German Center for Neurodegenerative Diseases (DZNE), 82152 Planegg, Germany; Chair of Developmental Genetics, Technische Universität München, 85354 Freising-Weihenstephan, Germany.
12
Institute of Stem Cell Research, Helmholtz Center Munich, 85764 Neuherberg, Germany; Department for Cell Biology and Anatomy, Biomedical Center of LMU, 82152 Planegg, Munich, Germany. Electronic address: ninkovic@helmholtz-muenchen.de.

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 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.

KEYWORDS:

aryl hydrocarbon receptor; direct conversion; live imaging; neurogenesis; regeneration; zebrafish

PMID:
30566853
DOI:
10.1016/j.celrep.2018.11.055
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