PUBLICATION

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

Authors
Di Giaimo, R., Durovic, T., Barquin, P., Kociaj, A., Lepko, T., Aschenbroich, S., Breunig, C.T., Irmler, M., Cernilogar, F.M., Schotta, G., Barbosa, J.S., Trümbach, D., Baumgart, E.V., Neuner, A.M., Beckers, J., Wurst, W., Stricker, S.H., Ninkovic, J.
ID
ZDB-PUB-181220-12
Date
2018
Source
Cell Reports   25: 3241-3251.e5 (Journal)
Registered Authors
Beckers, Johannes, Ninkovic, Jovica
Keywords
aryl hydrocarbon receptor, direct conversion, live imaging, neurogenesis, regeneration, zebrafish
Datasets
GEO:GSE121404, GEO:GSE102400
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Ependymoglial Cells/cytology
  • Ependymoglial Cells/metabolism
  • Mitosis
  • Neurogenesis*
  • Neurons/cytology
  • Receptors, Aryl Hydrocarbon/metabolism*
  • Signal Transduction*
  • Time Factors
  • Zebrafish
PubMed
30566853 Full text @ Cell Rep.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping