ArticleDevelopment (Cambridge, England)2021
Initiation of Otx2 expression in the developing mouse retina requires a unique enhancer and either Ascl1 or Neurog2 activity.
Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Ascl1 promotes OPC specification across species and central nervous system regions and its gliogenic function is regulated by phosphorylation.Developmental biology · 2026Article
- Echo characterizes the desynchronization of gene expression and chromatin accessibility during cell-state transitions.bioRxiv : the preprint server for biology · 2026Article
- A robust cis-regulatory network ensures Otx2 expression during retinal development.Development (Cambridge, England) · 2026Article
- Dicer is essential for proper maturation, composition, and function in the postnatal retina.iScience · 2025Article
- SOX2-VSX2 Co-Occupancy Shapes Retinal Neurogenesis Through Dynamic Chromatin Regulation.bioRxiv : the preprint server for biology · 2025Article
- Enhanced Transcriptional Activation in Developing Mouse Photoreceptors.Investigative ophthalmology & visual science · 2025Article
- SOX2-driven enhancer landscape defines the transcriptional architecture of retinogenesis.Development (Cambridge, England) · 2024Article
- The glucocorticoid receptor as a master regulator of the Müller cell response to diabetic conditions in mice.Journal of neuroinflammation · 2024Article
- Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury.Neural regeneration research · 2023Article
- Notch Signaling Plays a Dual Role in Regulating the Neuron-to-Oligodendrocyte Switch in the Developing Dorsal Forebrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Notch pathway mutants do not equivalently perturb mouse embryonic retinal development.PLoS genetics · 2023Article
- Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation.Nucleic acids research · 2023Article
- Regulation of the E/I-balance by the neural matrisome.Frontiers in molecular neuroscience · 2023Review
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- An enhancer located in a Pde6c intron drives transient expression in the cone photoreceptors of developing mouse and human retinas.Developmental biology · 2022Article
- Primary Cell Cultures to Study the Regeneration Potential of Murine Müller Glia after MicroRNA Treatment.Journal of visualized experiments : JoVE · 2022Article
- Review
- Building a Mammalian Retina: An Eye on Chromatin Structure.Frontiers in genetics · 2021Review
- Genetic and epigenetic regulators of retinal Müller glial cell reprogramming.Advances in ophthalmology practice and researchReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
During retinal development, a large subset of progenitors upregulates the transcription factor Otx2, which is required for photoreceptor and bipolar cell formation. How these retinal progenitor cells initially activate Otx2 expression is unclear. To address this, we investigated the cis-regulatory network that controls Otx2 expression in mice. We identified a minimal enhancer element, DHS-4D, that drove expression in newly formed OTX2+ cells. CRISPR/Cas9-mediated deletion of DHS-4D reduced OTX2 expression, but this effect was diminished in postnatal development. Systematic mutagenesis of the enhancer revealed that three basic helix-loop-helix (bHLH) transcription factor-binding sites were required for its activity. Single cell RNA-sequencing of nascent Otx2+ cells identified the bHLH factors Ascl1 and Neurog2 as candidate regulators. CRISPR/Cas9 targeting of these factors showed that only the simultaneous loss of Ascl1 and Neurog2 prevented OTX2 expression. Our findings suggest that Ascl1 and Neurog2 act either redundantly or in a compensatory fashion to activate the DHS-4D enhancer and Otx2 expression. We observed redundancy or compensation at both the transcriptional and enhancer utilization levels, suggesting that the mechanisms governing Otx2 regulation in the retina are flexible and robust.
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Registered trials
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.