PUBLICATION

dnmt1 function is required to maintain retinal stem cells within the ciliary marginal zone of the zebrafish eye

Authors
Angileri, K.M., Gross, J.M.
ID
ZDB-PUB-200711-6
Date
2020
Source
Scientific Reports   10: 11293 (Journal)
Registered Authors
Angileri, Krista, Gross, Jeffrey
Keywords
none
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • DNA (Cytosine-5-)-Methyltransferase 1/physiology*
  • Retinal Neurons/cytology
  • Retinal Neurons/physiology*
  • Stem Cells/cytology
  • Stem Cells/physiology*
  • Zebrafish/physiology*
  • Zebrafish Proteins/physiology*
PubMed
32647199 Full text @ Sci. Rep.
Abstract
The ciliary marginal zone (CMZ) of the zebrafish retina contains a population of actively proliferating resident stem cells, which generate retinal neurons throughout life. The maintenance methyltransferase, dnmt1, is expressed within the CMZ. Loss of dnmt1 function results in gene misregulation and cell death in a variety of developmental contexts, however, its role in retinal stem cell (RSC) maintenance is currently unknown. Here, we demonstrate that zebrafish dnmt1s872 mutants possess severe defects in RSC maintenance within the CMZ. Using a combination of immunohistochemistry, in situ hybridization, and a transgenic reporter assay, our results demonstrate a requirement for dnmt1 activity in the regulation of RSC proliferation, gene expression and in the repression of endogenous retroelements (REs). Ultimately, cell death is elevated in the dnmt1-/- CMZ, but in a p53-independent manner. Using a transgenic reporter for RE transposition activity, we demonstrate increased transposition in the dnmt1-/- CMZ. Taken together our data identify a critical role for dnmt1 function in RSC maintenance in the vertebrate eye.
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping