ArticlePLoS genetics2017
Tet-mediated DNA hydroxymethylation regulates retinal neurogenesis by modulating cell-extrinsic signaling pathways.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
- Ten-Eleven Translocation Enzymes Control the Rate and Mode of Retinal Progenitor Cell Division in the Developing Retina.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Global epigenetic immunohistochemical markers reveal developmental connections of distinct cell types during fetal development.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Emerging Trends and Hot Spots in Epigenetic Modifications in Neurology: A Bibliometric Analysis.Molecular neurobiology · 2025Review
- Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development.PLoS biology · 2025Article
- Investigation of mitochondrial DNA methylation-related prognostic biomarkers in hepatocellular carcinoma using The Cancer Genome Atlas (TCGA) database.Translational cancer research · 2025Article
- tet2 and tet3 regulate cell fate specification and differentiation events during retinal development.Scientific reports · 2025Article
- Tet3-mediated DNA demethylation is essential for maintaining the dedifferentiation capacity of mammalian Müller glia.Frontiers in molecular neuroscience · 2025Article
- Isolation and Preparation of Embryonic Zebrafish Retinal Cells for Single-Cell RNA Sequencing.Methods in molecular biology (Clifton, N.J.) · 2025Article
- tet2 and tet3 regulate cell fate specification and differentiation events during retinal development.bioRxiv : the preprint server for biology · 2024Article
- Epigenome-metabolism nexus in the retina: implications for aging and disease.Trends in genetics : TIG · 2024Review
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- Electrical stimulation alters DNA methylation and promotes neurite outgrowth.Journal of cellular biochemistry · 2023Article
- TET2 inhibits the proliferation and metastasis of lung adenocarcinoma cells via activation of the cGAS-STING signalling pathway.BMC cancer · 2023Article
- TET2 and TET3 loss disrupts small intestine differentiation and homeostasis.Nature communications · 2023Article
- Epigenetic Regulation of Corneal Epithelial Differentiation by TET2.International journal of molecular sciences · 2023Article
- Aging Effects on Optic Nerve Neurodegeneration.International journal of molecular sciences · 2023Review
- TET2 Promotes Keloid Hyperplasia by Regulating 5hmC Modification in the TGFβ Promoter Region.Clinical, cosmetic and investigational dermatology · 2023Article
- Epigenetic mechanisms of Müller glial reprogramming mediating retinal regeneration.Frontiers in cell and developmental biology · 2023Review
- The role of epigenetic methylation/demethylation in the regulation of retinal photoreceptors.Frontiers in cell and developmental biology · 2023Review
- Cephalopod retinal development shows vertebrate-like mechanisms of neurogenesis.Current biology : CB · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis. In tet2-/-;tet3-/- mutants, retinal neurons are specified but most fail to terminally differentiate. While differentiation of the first born retinal neurons, the retinal ganglion cells (RGCs), is less affected in tet2-/-;tet3-/- mutants than other retinal cell types, the majority of RGCs do not undergo terminal morphogenesis and form axons. Moreover, the few photoreceptors that differentiate in tet2-/-;tet3-/- mutants fail to form outer segments, suggesting that Tet function is also required for terminal morphogenesis of differentiated retinal neurons. Mosaic analyses revealed a surprising cell non-autonomous requirement for tet2 and tet3 activity in facilitating retinal neurogenesis. Through a combination of candidate gene analysis, transcriptomics and pharmacological manipulations, we identified the Notch and Wnt pathways as cell-extrinsic pathways regulated by tet2 and tet3 activity during RGC differentiation and morphogenesis. Transcriptome analyses also revealed the ectopic expression of non-retinal genes in tet2-/-;tet3-/- mutant retinae, and this correlated with locus-specific reduction in 5hmC. These data provide the first evidence that Tet-dependent regulation of 5hmC formation is critical for retinal neurogenesis, and highlight an additional layer of complexity in the progression from retinal progenitor cell to differentiated retinal neuron during development of the vertebrate retina.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.