Affinage

OTX2

Homeobox protein OTX2 · UniProt P32243

Length
289 aa
Mass
31.6 kDa
Annotated
2026-04-29
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTX2 is a paired-type homeodomain transcription factor that functions as a master regulator of anterior body plan specification, neural regionalization, retinal identity, and postnatal brain plasticity. It autonomously specifies anterior neuroectoderm fate, directs anterior visceral endoderm migration by activating Wnt and Nodal antagonists (Dkk1, Lefty1), and positions the midbrain–hindbrain boundary through mutual repression with Gbx2 and FGF8, recruiting Groucho/TLE corepressors via eh1-like motifs to context-dependent cis-regulatory modules (PMID:7590242, PMID:10704829, PMID:17060451, PMID:25005894, PMID:11171400, PMID:25231759). In the retina, OTX2 specifies photoreceptor and bipolar cell fates while repressing alternative retinal neuron identities, and in the adult RPE it maintains photoreceptor survival non-cell-autonomously through a direct transcriptional program defined by ChIP-seq (PMID:32347797, PMID:20657788, PMID:23761884, PMID:17908793). Beyond the eye, OTX2 cooperates with Sox2 to activate eye-field genes such as Rax, drives exit from naive pluripotency by pioneering enhancer activation with Oct4 in ESCs, specifies VTA dopaminergic and glutamatergic thalamic neuron subtypes, regulates GnRH neuron function and fertility, controls choroid plexus development and CSF composition, and transfers non-cell-autonomously into cortical parvalbumin interneurons where it regulates critical-period plasticity via Gadd45b/g transcription (PMID:18385377, PMID:24931607, PMID:21057506, PMID:16738237, PMID:21436260, PMID:23364326, PMID:29771284). OTX2 is amplified in medulloblastoma, where it directly activates cell-cycle genes, maintains bivalent chromatin through PRC2, and represses differentiation programs including the MyoD1 enhancer (PMID:21964830, PMID:23179372, PMID:22986744, PMID:32686664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1994 High

    Establishing that Otx2 expression in anterior ectoderm requires positive signals from anterior mesendoderm and is repressed by posterior signals and retinoic acid resolved how the anterior Otx2 domain is initially delimited.

    Evidence Explant-recombination assays with retinoic acid treatment in mouse embryos

    PMID:7607086

    Open questions at the time
    • Upstream signaling molecules from anterior mesendoderm not identified
    • Whether RA acts directly on Otx2 regulatory elements was unknown
  2. 1995 High

    The Otx2 knockout demonstrated it is absolutely required for formation of all structures anterior to rhombomere 3, establishing its role as a gap-like master gene for rostral head specification.

    Evidence Targeted gene knockout in mouse with homozygous and heterozygous phenotypic analysis

    PMID:7590242

    Open questions at the time
    • Direct transcriptional targets unknown
    • Cell-autonomous versus non-autonomous contributions not separated
  3. 1997 High

    Demonstrating that Otx2 directly activates the cement gland marker XCG without de novo protein synthesis, and autoregulates its own expression, established Otx2 as a direct transcriptional activator with positive autoregulation.

    Evidence Dexamethasone-inducible Otx2-GR fusion with cycloheximide block in Xenopus

    PMID:9053323

    Open questions at the time
    • Genomic binding sites not mapped
    • Whether autoregulation operates through specific enhancers was unresolved
  4. 1999 High

    Ectopic Otx2 expression in anterior hindbrain shifted the isthmic organizer caudally, and reciprocal Otx2–Gbx2 gain-of-function showed mutual repression, establishing that the Otx2 expression boundary is sufficient to position the midbrain–hindbrain organizer.

    Evidence Knock-in of Otx2 into En1 locus in mouse; in ovo electroporation in chick with Otx2 and Gbx2

    PMID:10021338 PMID:10490025 PMID:10704829

    Open questions at the time
    • Mechanism of mutual repression (direct versus indirect) not determined
    • Whether Otx2-Gbx2 repression requires cofactors was unknown
  5. 1999 High

    Replacement of Otx1 coding sequence with human OTX2 rescued Otx1−/− phenotypes, establishing that Otx1 and Otx2 proteins are functionally equivalent and phenotypic differences arise from expression pattern divergence.

    Evidence Knock-in of human OTX2 cDNA into mouse Otx1 locus with phenotypic rescue analysis

    PMID:10068635

    Open questions at the time
    • Whether any subtle functional differences exist was not exhaustively tested
  6. 1999 Medium

    Biochemical characterization showed OTX2 binds DNA cooperatively as a dimer, requiring both the homeodomain and C-terminal region, defining the molecular basis of OTX2 DNA recognition.

    Evidence EMSA with recombinant full-length OTX2 and systematic deletion mutants

    PMID:10069392

    Open questions at the time
    • No structural data for the dimer
    • In vivo relevance of dimerization not tested
  7. 2001 High

    Lineage tracing in Otx2 mutants revealed that Otx2 is required in the anterior visceral endoderm for its directional morphogenetic movement and for expression of secreted Nodal/Wnt antagonists, separating its endoderm-autonomous role from neuroectoderm specification.

    Evidence Lineage tracing combined with molecular marker analysis in Otx2 mutant mouse embryos

    PMID:11171400

    Open questions at the time
    • Whether Otx2 directly activates Lefty1 and Dkk1 was not yet tested
  8. 2004 High

    Conditional Otx2 deletion in ventral midbrain progenitors showed Otx2 is required for dopaminergic neuron specification by repressing Nkx2.2 and maintaining Nkx6.1, establishing its role as a neuronal subtype determinant beyond regional patterning.

    Evidence Conditional Cre-mediated Otx2 inactivation under En1 control in mouse; Nestin-Cre conditional KO

    PMID:15105370 PMID:15888661

    Open questions at the time
    • Whether Otx2 directly binds Nkx2.2 regulatory regions not tested
    • Mechanism of Otx2 interaction with Shh pathway unclear
  9. 2006 High

    Identification of eh1-like motifs mediating Otx2–Groucho/TLE interaction, and systematic domain mapping of transactivation, DNA-binding, nuclear retention, and dominant-negative regions, defined the modular architecture underlying Otx2's context-dependent activator/repressor functions.

    Evidence Co-immunoprecipitation and in vivo heat-shock expression in medaka; systematic deletion/point mutagenesis with functional assays

    PMID:16607563 PMID:17060451

    Open questions at the time
    • Structural basis of Groucho interaction not resolved
    • How disease mutations differentially affect different protein domains in vivo not tested
  10. 2006 High

    Conditional Otx2 ablation in thalamic progenitors revealed it represses GABAergic fate by suppressing Mash1 in glutamatergic progenitors, extending Otx2's subtype-specification role to the diencephalon.

    Evidence Conditional thalamus-specific Otx2 ablation with molecular marker analysis in mouse

    PMID:16738237

    Open questions at the time
    • Whether Otx2 directly binds Mash1 regulatory elements not determined
  11. 2007 High

    Discovery that acetylated YY1 binds both the distant AN enhancer and the Otx2 promoter to drive anterior neuroectoderm expression revealed an evolutionarily conserved long-range regulatory mechanism for Otx2 transcription.

    Evidence ChIP; transgenic reporter and enhancer-mutant mice

    PMID:17332747

    Open questions at the time
    • Whether additional transcription factors bridge enhancer-promoter contact unknown
    • Chromatin looping mechanism not demonstrated
  12. 2007 High

    Otx2 was shown to function in the postnatal retina by contributing to photoreceptor terminal differentiation (synergizing with Crx) and maintaining mature bipolar cell identity and function.

    Evidence Double Otx2/Crx conditional KO; bipolar-specific Otx2 conditional KO with ERG in mouse

    PMID:17908793

    Open questions at the time
    • Direct transcriptional targets in bipolar cells not identified
  13. 2008 High

    Physical interaction between Otx2 and Sox2 on the Rax enhancer, with synergistic transcriptional activation disrupted by disease-associated Sox2 mutations, established a cooperative Otx2–Sox2 axis in eye field specification.

    Evidence ChIP, co-immunoprecipitation, luciferase reporter, and mutagenesis in Xenopus

    PMID:18385377

    Open questions at the time
    • Whether other eye-field TFs participate in the same complex unknown
  14. 2010 High

    RPE-specific conditional KO and rescue demonstrated that Otx2 maintains photoreceptor survival non-cell-autonomously through RPE transcriptional programs, resolving the longstanding question of why Otx2 loss causes photoreceptor degeneration.

    Evidence Conditional self-knockout; RPE-specific rescue; ERG and gene expression analysis

    PMID:20657788

    Open questions at the time
    • Identity of RPE-secreted survival factors downstream of Otx2 not defined
  15. 2010 High

    Otx2 was shown to define VTA dopaminergic neuron identity by antagonizing SNc-specific Girk2 and Dat expression, with ectopic Otx2 conferring MPTP resistance, establishing Otx2 as a subtype selector within the dopaminergic system.

    Evidence Bidirectional genetic manipulation in mouse with molecular markers and MPTP challenge

    PMID:21057506

    Open questions at the time
    • Direct Otx2 binding sites at Girk2 and Dat not mapped
    • Whether Otx2 expression can be therapeutically maintained for neuroprotection untested
  16. 2011 High

    ChIP-on-chip revealed OTX2 directly binds cell-cycle gene promoters in medulloblastoma, and its silencing inhibits proliferation while inducing neuronal differentiation, establishing OTX2 as an oncogenic transcription factor in this cancer.

    Evidence Inducible shRNA knockdown; ChIP-on-chip; expression profiling in D425 medulloblastoma cells

    PMID:15705891 PMID:21964830

    Open questions at the time
    • Whether OTX2 amplification is sufficient for tumor initiation not established
  17. 2012 High

    OTX2 was found to maintain bivalent chromatin at its target promoters by sustaining PRC2 expression and H3K27me3 levels, and to repress differentiation by directly binding the MyoD1 enhancer, defining its epigenetic mechanism in medulloblastoma.

    Evidence Inducible OTX2 shRNA with ChIP for histone marks; ChIP at MyoD1 enhancer; in vivo orthotopic models

    PMID:22986744 PMID:23179372

    Open questions at the time
    • Whether PRC2 is a direct or indirect OTX2 target not fully resolved
    • Contribution of individual bivalent targets to tumorigenesis unclear
  18. 2013 High

    ChIP-seq in adult RPE defined the genome-wide Otx2 target network underlying RPE maintenance, while conditional deletion showed Otx2 controls choroid plexus development and CSF composition influencing distant cortical proliferation, broadening Otx2's adult roles beyond the retina.

    Evidence RPE-specific conditional KO with ChIP-seq; temporal Otx2 deletion in choroid plexus with CSF analysis

    PMID:23364326 PMID:23761884

    Open questions at the time
    • Whether ChP-derived Otx2 targets fully account for CSF signaling changes not determined
  19. 2014 High

    Genome-wide ChIP-seq in Xenopus gastrulae revealed Otx2 occupies tissue-specific CRMs together with TLE/Groucho, with activator or repressor output determined by partner TFs (Lhx1 vs Goosecoid), providing a unified model for context-dependent Otx2 transcriptional activity.

    Evidence ChIP-seq for Otx2 and TLE; RNA-seq; CRM classification in Xenopus tropicalis

    PMID:25005894

    Open questions at the time
    • How cofactor exchange is regulated at specific loci unknown
    • Whether similar CRM logic operates in mammalian tissues not tested
  20. 2014 High

    Otx2 was established as a pioneer-like factor driving enhancer activation during ESC exit from naive pluripotency, forming a reciprocal regulatory axis with Oct4 and antagonizing Nanog to promote primed identity.

    Evidence ChIP-seq for Otx2, Oct4, histone marks in ESCs; Otx2 KO/overexpression; 2i/FGF assays

    PMID:24931607 PMID:29056334

    Open questions at the time
    • Whether Otx2 directly remodels chromatin or recruits remodelers is unresolved
    • In vivo relevance for epiblast differentiation not formally tested
  21. 2014 High

    Direct ChIP evidence showed OTX2 activates Dkk1 and Lhx1 in anterior mesendoderm, and compound mutant analysis confirmed genetic synergy, closing the gap on how Otx2 controls head induction at the target-gene level.

    Evidence ChIP-qPCR; luciferase assay; compound Otx2;Lhx1 and Otx2;Dkk1 mutant analysis

    PMID:25231759

    Open questions at the time
    • Full complement of direct AME targets not catalogued
  22. 2019 High

    Identification of Gadd45b/g as direct OTX2 transcriptional targets in cortical parvalbumin interneurons, with Gadd45b sufficient to reopen ocular dominance plasticity in adults, established the downstream effector mechanism of non-cell-autonomous OTX2 transfer in critical-period regulation.

    Evidence OTX2 cortical infusion; Otx2+/GFP mice; viral Gadd45b overexpression; OD plasticity and methylation assays

    PMID:29771284

    Open questions at the time
    • How OTX2 protein transfers into PV interneurons mechanistically unresolved
    • Whether other homeoprotein transfers use the same Gadd45-mediated pathway unknown
  23. 2020 High

    Single-cell transcriptomics after CRISPR OTX2 deletion in chick retina revealed OTX2 not only promotes photoreceptor fate but actively represses specific ganglion and horizontal cell subtypes, redefining it as a dual fate-selector in retinogenesis; in medulloblastoma, multi-omic analysis identified a PAX3–mTORC1 axis downstream of OTX2 silencing.

    Evidence CRISPR/Cas9 somatic KO with scRNA-seq in chick retina; OTX2 silencing with multi-omics and in vivo survival in medulloblastoma

    PMID:32347797 PMID:32686664

    Open questions at the time
    • Mechanism by which OTX2 represses RGC/HC identity at specific loci not mapped
    • Whether mTORC1 inhibition can substitute for OTX2 targeting in therapy not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of OTX2 cooperative DNA binding and dimerization, the precise mechanism by which OTX2 homeoprotein transfers intercellularly into parvalbumin neurons, how cofactor switching at shared CRMs is regulated in different tissues, and whether therapeutic modulation of OTX2 can be achieved in medulloblastoma or retinal degeneration.
  • No crystal/cryo-EM structure of OTX2 bound to DNA
  • Intercellular transfer mechanism not molecularly defined
  • Therapeutic targeting strategies not developed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 14 GO:0003677 DNA binding 11
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 13 R-HSA-74160 Gene expression (Transcription) 8 R-HSA-112316 Neuronal System 5 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 3
Partners
FOXA2GBX2LHX1MITFPOU5F1SOX2SOX9TLE1
Complex memberships
Otx2–Lhx1–Foxa2–Ldb1 (anterior mesendoderm)Otx2–TLE/Groucho (corepressor)

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Otx2 is essential for formation of all structures anterior to rhombomere 3; homozygous knockout mice fail to develop the rostral head, demonstrating Otx2 functions as a gap-like gene in the Hox-free rostral head region. Heterozygous loss causes craniofacial malformations (otocephaly) in regions where Otx1 is not co-expressed. Targeted gene knockout in mouse (homozygous and heterozygous mutant phenotypic analysis) Genes & development High 7590242
1994 Anterior mesendoderm provides a positive signal required to stabilize Otx2 expression in ectoderm, while posterior mesendoderm provides a negative (repressive) signal; exogenous retinoic acid can mimic the posterior repressive signal and reduce the anterior Otx2 domain. Explant-recombination assays in mouse embryos; retinoic acid treatment Development (Cambridge, England) High 7607086
1999 The caudal limit of Otx2 expression is sufficient to position the isthmic organizer and specify midbrain versus hindbrain fate; ectopic Otx2 expression in the presumptive anterior hindbrain (via En1 locus knock-in) shifts the isthmic organizer markers (Pax2, Fgf8, Wnt1, Gbx2) caudally and causes loss of anterior cerebellar vermis with complementary enlargement of inferior colliculus. Knock-in strategy into En1 locus to ectopically express Otx2; histological and molecular marker analysis Nature High 10490025
1999 FGF8 represses Otx2 expression in the chick neuroepithelium, and a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain; FGF8-bead implantation induces an ectopic isthmic organizer by repressing Otx2 and inducing En1, Fgf8, and Wnt1. FGF8-bead implantation in chick embryos; in situ hybridization for molecular markers Development (Cambridge, England) High 10021338
2000 Otx2 and Gbx2 mutually repress each other's expression at the midbrain-hindbrain boundary; ectopic Otx2 in chick metencephalon transforms it into optic tectum, ectopic Gbx2 in mesencephalon shifts the tectum's caudal limit rostrally, and both repress endogenous Fgf8 while inducing Fgf8 at their new expression interface. In ovo electroporation gain-of-function in chick embryos; expression analysis of isthmic/tectum markers Mechanisms of development High 10704829
2001 Otx2 is required in the anterior visceral endoderm for anteriorly directed morphogenetic movement and for expression of secreted antagonists of Nodal (Lefty1) and Wnt (Dkk1) signals; Otx2 mutants show failure of anterior visceral endoderm migration and ectopic primitive streak marker expression in the epiblast. Lineage tracing combined with molecular marker analysis in Otx2 mutant mouse embryos Development (Cambridge, England) High 11171400
1997 Otx2 directly activates the cement gland differentiation marker XCG (in the absence of protein synthesis, indicating direct target activation) and also autoregulates its own expression; retinoic acid blocks Otx2 autoactivation, explaining how RA reduces the anterior Otx2 domain. Dexamethasone-inducible Otx2-GR fusion protein; cycloheximide block experiments; reporter assays in Xenopus Development (Cambridge, England) High 9053323
2000 OTX2 directly binds LIM1 (via its C-terminal region to the LIM1 homeodomain) and HNF-3β (via both homeodomain and C-terminal regions); LIM1 enhances OTX2-directed transcription while HNF-3β represses it at a P3C binding sequence. Co-immunoprecipitation; deletion mutagenesis; luciferase transactivation assay Biochemical and biophysical research communications Medium 10623575
1999 The divergent phenotypes of Otx1-/- and Otx2-/- mice largely reflect differences in expression patterns rather than coding sequence; human OTX2 cDNA knocked into the Otx1 locus rescues epilepsy, corticogenesis, and most other Otx1-/- defects, demonstrating extended functional homology between OTX1 and OTX2 proteins. Knock-in replacement of Otx1 coding sequence with human OTX2 cDNA; phenotypic rescue analysis Development (Cambridge, England) High 10068635
2000 OTX2 binds a bicoid-related Otx target sequence in the GnRH proximal promoter using baculovirus-expressed OTX2 and nuclear extracts from GT1-7 cells; Otx2 overexpression induces GnRH promoter activity in GT1-7 neurons in an Otx binding site-dependent manner, and OTX2 protein is present in adult GnRH neurons. Electrophoretic mobility shift assay (EMSA); transient transfection/luciferase reporter assay; immunohistochemistry Molecular endocrinology (Baltimore, Md.) Medium 10935548
1997 Human OTX2 homeodomain protein binds with high affinity to a target sequence (OTS) in the human tenascin-C promoter and trans-represses its transcriptional activity in transiently transfected cells. EMSA with recombinant protein; transient transfection reporter assay DNA and cell biology Medium 9174161
1999 OTX2 binding to its DNA target (OTS) recruits a second OTX2 molecule to the complex cooperatively; the C-terminal region carboxyl to the homeodomain is required in addition to the homeodomain for DNA binding; OTX2 dimerization requires the same protein domains as DNA binding. EMSA with full-length recombinant OTX2 and deletion mutants FEBS letters Medium 10069392
2004 Otx2 regulates identity and fate of ventral midbrain neuronal progenitors by repressing Nkx2.2 and maintaining the Nkx6.1-expressing domain through dorsal antagonism on Shh; loss of Otx2 causes dopaminergic neurons to be greatly reduced, red nucleus precursors to disappear, and serotonergic neurons to be generated in the ventral midbrain. Conditional Cre-mediated Otx2 inactivation under En1 transcriptional control; molecular marker analysis in mouse Development (Cambridge, England) High 15105370
2005 Otx2 controls neuronal subtype identity and neurogenesis in the midbrain independently of its role in positioning the mid-hindbrain organizer; loss of Otx2 in neuronal progenitors from E10.5 leads to ectopic Math1 expression and cerebellar-like structure in dorsal midbrain, ectopic Nkx2.2 and serotonergic neurons ventrally, and hypoplasia of the red nucleus and dopaminergic neurons. Conditional Nestin-Cre/Otx2(flox/flox) knockout mice; molecular marker and histological analysis The Journal of neuroscience High 15888661
2006 Otx2 is cell-autonomously required in glutamatergic dorsal thalamus progenitors to repress GABAergic differentiation by repressing Mash1 in Ngn2-expressing progenitors; Otx2 ablation also activates Pax3, Pax7, and Lim1, markers of pretectal GABAergic identity, and causes hyperproliferation. Conditional Otx2 ablation in thalamus; in situ hybridization and molecular marker analysis in mouse The Journal of neuroscience High 16738237
2006 Gbx2 and Otx2 both interact physically with the WD40 domain of Groucho/Tle corepressor proteins via engrailed homology region 1 (eh1)-like motifs; Groucho is required for Gbx2-mediated repression of Otx2 and for Otx2-mediated repression of Fgf8 at the MHB in medaka embryos. Cell culture colocalization; co-immunoprecipitation; heat shock-induced expression of wild-type and mutant proteins in medaka embryos Molecular and cellular biology High 17060451
2006 Molecular characterization of OTX2 identifies: transactivation domains in both N- and C-termini; DNA binding residing in the minimal homeodomain with critical residues identified; a nuclear localization sequence within the homeodomain; a novel nuclear retention domain in the central protein region; and a dominant negative activity in the central region. Human disease mutations show decreased transactivation activity rather than dominant negative effect. Deletion and point mutant analysis; transactivation assay; DNA binding assay; subcellular localization analysis in transfected cells Journal of molecular medicine (Berlin, Germany) High 16607563
2008 Otx2 and Sox2 proteins physically interact with each other and both bind to the conserved noncoding sequence CNS1 ~2 kb upstream of the Rax promoter; Otx2 and Sox2 synergistically activate Rax transcription via CNS1; ocular malformation-associated Sox2 missense mutations disrupt the Sox2-Otx2 interaction. ChIP with endogenous proteins; reporter/luciferase assay; co-immunoprecipitation; mutagenesis in Xenopus Proceedings of the National Academy of Sciences of the United States of America High 18385377
2007 Otx2 acts as a competence factor for lens specification by binding to the major FoxE3 enhancer (Lens1) together with Su(H) (the Notch signaling nuclear transducer); both inputs are obligately required for FoxE3 activation in the presumptive lens ectoderm. In vivo and in vitro binding assays; deletion/mutation analysis of enhancer; inhibition of Notch ligand Delta2; ectopic Notch activation in Xenopus Development (Cambridge, England) High 18057103
2009 Wnt/β-catenin signaling directly regulates Otx2 expression in the developing RPE; β-catenin binds near TCF/LEF sites in the Otx2 enhancer as shown by ChIP and luciferase assays; RPE-specific β-catenin deletion causes downregulation of Otx2 and Mitf and transdifferentiation of RPE into retina. Cre-mediated conditional RPE-specific β-catenin knockout; ChIP; luciferase enhancer assay; immunohistochemistry Development (Cambridge, England) High 19553286
2010 Otx2 controls neuron subtype identity in the VTA by antagonizing Girk2 and Dat expression; Otx2 is restricted to VTA neurons complementary to those with high Dat and Girk2; Otx2 loss expands the dorsal-lateral VTA identity, while ectopic Otx2 in substantia nigra suppresses Dat expression and confers MPTP resistance. Loss-of-function and gain-of-function mouse models; molecular marker analysis; MPTP neurotoxin challenge Nature neuroscience High 21057506
2010 Conditional adult Otx2 ablation causes slow photoreceptor degeneration and rapid RPE dysfunction; RPE-specific Otx2 deletion alone recapitulates photoreceptor degeneration, while constitutive Otx2 expression restricted to RPE prevents degeneration, establishing that Otx2 maintains photoreceptors non-cell-autonomously through RPE function. Conditional self-knockout (CreERT2/flox strategy); electroretinography; gene expression analysis; RPE-specific rescue experiment PloS one High 20657788
2011 OTX2 directly binds to cell cycle gene promoters (identified by ChIP-on-chip) and activates their expression in medulloblastoma cells; silencing OTX2 inhibits proliferation and induces neuronal differentiation, with downregulation of cell cycle and visual perception genes and upregulation of differentiation genes. Inducible shRNA knockdown; expression profiling; ChIP-on-chip in D425 medulloblastoma cells International journal of cancer High 21964830
2005 OTX2 is amplified and overexpressed in medulloblastoma; siRNA-mediated OTX2 knockdown inhibits medulloblastoma cell growth in vitro; pharmacological all-trans retinoic acid represses OTX2 expression and induces apoptosis specifically in OTX2-expressing medulloblastoma cell lines. siRNA knockdown; digital karyotyping; gene expression analysis; pharmacological treatment (ATRA) Cancer research Medium 15705891
2009 OTX2 ectopic expression enhances proliferation and tumorigenicity of immortalized primary cells; OTX2 knockdown in medulloblastoma cells prolongs survival in xenograft tumor models; MYC upregulation is identified as a potential mechanism by which OTX2 promotes tumor progression. Ectopic OTX2 expression; shRNA knockdown; orthotopic xenograft mouse model; expression analysis Cancer research Medium 20028867
2012 OTX2 binds to the MyoD1 core enhancer through its homeobox domain and represses myogenic and neuronal differentiation in medulloblastoma cells; the homeobox domain exhibits strong repressor activity; OTX2 attenuation triggers myogenic and neuronal differentiation in vitro and prolongs survival in an orthotopic mouse model. ChIP; DNA binding assay; RNAi knockdown; in vitro differentiation assay; orthotopic mouse model Cancer research High 22986744
2012 OTX2 silencing in medulloblastoma causes downregulation of polycomb genes (EZH2, EED, SUZ12, RBBP4) and upregulation of H3K27 demethylases, resulting in decreased H3K27me3 particularly at OTX2-bound promoters; OTX2-bound promoters exhibit a bivalent-like state with high H3K4me3/H3K9ac and intermediate H3K27me3 that is maintained by OTX2. Inducible OTX2 shRNA; ChIP for histone marks; gene expression analysis in D425 cells Acta neuropathologica Medium 23179372
2013 Loss of Otx2 in the adult mouse RPE (by RPE-specific conditional ablation) disrupts four RPE-specific functions identified by ChIP-seq, leading to photoreceptor degeneration; ChIP-seq identifies the in vivo Otx2 target gene network in RPE cells; many direct Otx2 RPE targets are associated with human retinopathies. RPE-specific conditional Otx2 KO; electroretinography; ChIP-seq; gene expression analysis The Journal of neuroscience High 23761884
2013 Otx2 is essential for choroid plexus (ChP) development and maintenance; Otx2 deletion at E9 eliminates all ChPs; Otx2 deletion at E15 in hindbrain ChP causes apoptosis and reduced size; Otx2 controls CSF composition including Wnt4 and Tgm2 levels, thereby influencing Wnt signaling and proliferation in the distant cerebral cortex. Conditional Otx2 deletion using Otx2-CreERT2 and Gdf7-Cre driver lines; histological, apoptosis, and gene expression analysis Development (Cambridge, England) High 23364326
2014 Otx2 drives enhancer activation during exit from ground state pluripotency by affecting chromatin marks; Oct4 is required for Otx2 expression, and reciprocally Otx2 is required for efficient Oct4 recruitment to many enhancer regions, establishing an Oct4-Otx2 regulatory axis. ChIP-seq for Otx2, Oct4, and histone marks in mouse ESCs; genetic knockdown/KO; gene expression analysis Cell reports High 24931607
2014 Sox6 and Otx2 define complementary dopamine neuron subpopulations: Sox6 is selective for SNc neurons while Otx2 and Nolz1 mark VTA neurons; Sox6 ablation decreases SNc markers and increases VTA markers while Otx2 ablation has the opposite effect, demonstrating mutual antagonism in subtype specification. Conditional knockout of Sox6 and Otx2; molecular marker and electrophysiological analysis; dopamine measurement Cell reports High 25127144
2014 OTX2 directly activates Dkk1 expression in the anterior mesendoderm by interacting with the Dkk1 H1 regulatory region; OTX2 binds two conserved regions in the Lhx1 locus to activate Lhx1 expression; compound Otx2;Lhx1 and Otx2;Dkk1 mutants show severely abnormal head development. Tissue-specific conditional Otx2 ablation in AME; ChIP-qPCR; luciferase assay; RT-qPCR; compound mutant analysis Development (Cambridge, England) High 25231759
2014 ChIP-seq in Xenopus tropicalis gastrulae reveals Otx2 occupies tissue-specific cis-regulatory modules (CRMs) together with TLE/Groucho corepressor; two distinct CRM types mediate activation or repression of target genes depending on whether partner TFs (e.g., Lim1/Lhx1 activator or Goosecoid repressor) are present. ChIP-seq for Otx2 and TLE in Xenopus gastrulae; RNA-seq; CRM profiling Nature communications High 25005894
2014 Otx2 ChIP-seq in the mature mouse retina shows Otx2 occupies different genomic functional domains in RPE versus neural retina cells, regulating mostly different gene sets; in neural retina, Otx2 genome occupancy largely overlaps with the related transcription factor Crx, consistent with functional redundancy in that compartment. ChIP-seq for Otx2 in RPE and neural retina; comparison with Crx ChIP-seq data PloS one High 24558479
2007 Acetylated YY1 binds to both the Otx2 anterior neuroectoderm (AN) enhancer (92 kb upstream) and the promoter region; only acetylated YY1 binds the enhancer sequence; YY1 binding to both sites is required for Otx2 expression in anterior neuroectoderm, and this regulatory mechanism is evolutionarily conserved. Chromatin immunoprecipitation; transgenic reporter assay; enhancer mutant mice (Otx2ΔAN/-); conservation analysis The EMBO journal High 17332747
2010 SOX9 physically interacts with MITF and OTX2 and, together with them, synergistically activates the BEST1 promoter through a paired SOX site; ChIP on fresh RPE cells confirms SOX9 binding to the BEST1 region. Co-immunoprecipitation; ChIP; siRNA knockdown; luciferase reporter assay; yeast one-hybrid screen The Journal of biological chemistry Medium 20530484
2000 Otx2 protein shows cell-type-specific subcellular localization in the postnatal retina: nuclear in RPE and bipolar cells, but cytoplasmic in rod photoreceptors; cytoplasmic retention in immature rods is developmentally regulated, as shown in retinal explants and transfected cell lines. Immunohistochemistry; retinal explant culture; cell line transfection; subcellular fractionation Brain research. Molecular brain research Medium 10891582
2011 Deletion of Otx2 specifically in GnRH neurons causes a significant decrease in hypothalamic GnRH neurons, delayed pubertal onset, abnormal estrous cyclicity, and infertility, providing in vivo evidence that Otx2 is required for GnRH expression and reproductive competence. GnRH neuron-specific Otx2 conditional knockout; neuron counting; reproductive phenotype analysis Molecular endocrinology (Baltimore, Md.) High 21436260
2015 In iPSC-derived 3D organoids modeling congenital pituitary hypoplasia, OTX2 in the hypothalamus (not in oral ectoderm) is required for pituitary progenitor cell maintenance by regulating LHX3 expression in oral ectoderm via FGF10 in the hypothalamus; haploinsufficiency of OTX2 impairs pituitary hormone-producing cell differentiation. Patient-derived iPSCs; 3D organoid differentiation; mutation correction; gene expression analysis The Journal of clinical investigation High 31845906
2014 Otx2 deletion in pituitary neural ectoderm abolishes FGF signaling and causes severe hypoplasia of the posterior pituitary lobe and stalk; lack of FGF signaling from the neural ectoderm also impairs anterior lobe growth (but not cell differentiation), demonstrating both cell-intrinsic and extrinsic roles of Otx2 in pituitary development. Multiple Cre driver lines for tissue-specific Otx2 deletion; histological and gene expression analysis Human molecular genetics Medium 25315894
2019 Non-cell autonomous OTX2 homeoprotein transferred into the visual cortex directly regulates Gadd45b/g transcription, inducing their expression in juvenile mice; in adults, reducing cortical OTX2 increases Gadd45b/g expression. Viral Gadd45b expression in adult visual cortex directly induces ocular dominance plasticity with epigenetic changes (MeCP2 foci, methylation of plasticity gene promoters) in parvalbumin interneurons. OTX2 cortical infusion; Otx2+/GFP mice; gene expression analysis; viral Gadd45b overexpression; ocular dominance plasticity assay; MeCP2 and methylation analysis Cerebral cortex (New York, N.Y. : 1991) High 29771284
2016 Hmga2 is required for Otx2-dependent exit of ESCs from pluripotent ground state; Hmga2 associates with Otx2-bound enhancer loci in EpiLCs and is required for Otx2 binding to and activation of new enhancers during differentiation; a positive feedback loop exists as Hmga2 is itself an Otx2 target gene. ChIP in ESCs/EpiLCs; Hmga2 KO iPSCs; gene expression analysis; comparison of Otx2 ChIP in WT vs KO BMC biology Medium 27036552
2017 OTX2 and NANOG are functionally antagonistic in specifying ESC identity: ESCs lacking Nanog or overexpressing Otx2 adopt an early primed identity and fail to revert to naive state; Otx2-null ESCs exhibit naive identity features and convert poorly into primed state; loss of both drives primed identity with weakened naive conversion. Genetic KO and overexpression in mouse ESCs; 2i and FGF-treatment assays; gene expression analysis Stem cell reports Medium 29056334
2020 OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification; CRISPR/Cas9 somatic OTX2 mutations in chick retina combined with single-cell RNA-seq show OTX2 is required not only for photoreceptor generation but also for repression of specific retinal ganglion cell and horizontal cell subtypes. CRISPR/Cas9 somatic gene editing in chick retina; single-cell RNA sequencing eLife High 32347797
2020 OTX2 silencing in Group 3 medulloblastoma modulates the repressive chromatin landscape, decreases PRC2 complex genes, and increases PAX3 and PAX6; PAX3 (but not PAX6) inhibits self-renewal and increases survival in vivo; mTORC1 signaling is identified as a downstream effector of the OTX2-PAX3 axis. OTX2 silencing; multi-omic analysis (chromatin, expression); single-cell RNA-seq; PAX3/PAX6 functional assays; in vivo survival assay Nature communications High 32686664
2015 Lhx1 forms a protein complex with Otx2, Foxa2, and the chromatin-looping protein Ldb1 in the anterior mesendoderm, as demonstrated by proteomic co-immunoprecipitation; Lhx1-binding sites are enriched at enhancers controlling Otx2 and Foxa2 expression (identified by ChIP-seq). Proteomic co-immunoprecipitation; ChIP-seq for Lhx1; conditional KO Genes & development Medium 26494787
2007 Functional roles of Otx2 in postnatal retina: Otx2 contributes to terminal differentiation of photoreceptors (demonstrated by Otx2+/-;Crx-/- double KO showing enhanced degeneration); conditional bipolar-cell-specific Otx2 KO causes downregulation of protein kinase C (mature bipolar cell marker) and impaired bipolar cell electroretinographic function. Double conditional knockout (Otx2/Crx); bipolar cell-specific conditional Otx2 KO; immunohistochemistry; electroretinography Molecular and cellular biology High 17908793
2016 TNF-α secreted from activated monocytes mediates downregulation of OTX2 and essential RPE genes (including visual cycle genes) in RPE cells, demonstrating that OTX2 expression is regulated by inflammatory signals in the adult retina. Coculture of monocytes with porcine RPE and human iPSC-derived RPE; TNF-α neutralization/antibody blockade; gene expression analysis Aging cell Medium 27660103

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Mouse Otx2 functions in the formation and patterning of rostral head. Genes & development 591 7590242
1999 FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Development (Cambridge, England) 325 10021338
1994 Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants. Development (Cambridge, England) 295 7607086
1999 The caudal limit of Otx2 expression positions the isthmic organizer. Nature 255 10490025
2005 Heterozygous mutations of OTX2 cause severe ocular malformations. American journal of human genetics 250 15846561
2004 Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain. Development (Cambridge, England) 174 15105370
1999 Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. Development (Cambridge, England) 172 10225993
1995 c-otx2 is expressed in two different phases of gastrulation and is sensitive to retinoic acid treatment in chick embryo. Mechanisms of development 171 7748789
2007 Functional roles of Otx2 transcription factor in postnatal mouse retinal development. Molecular and cellular biology 159 17908793
2006 Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2. Clinical genetics 149 16712695
2009 Beta-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development (Cambridge, England) 146 19553286
1997 Identification of otx2 target genes and restrictions in ectodermal competence during Xenopus cement gland formation. Development (Cambridge, England) 133 9053323
1997 Implication of OTX2 in pigment epithelium determination and neural retina differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 128 9151741
2014 Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons. Cell reports 123 25127144
2005 Otx2 regulates subtype specification and neurogenesis in the midbrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 121 15888661
2001 Otx2 is required for visceral endoderm movement and for the restriction of posterior signals in the epiblast of the mouse embryo. Development (Cambridge, England) 121 11171400
2000 Interaction between Otx2 and Gbx2 defines the organizing center for the optic tectum. Mechanisms of development 121 10704829
2005 Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid. Cancer research 114 15705891
2013 The homeobox gene Otx2 in development and disease. Experimental eye research 112 23523800
1998 Otx1 and Otx2 in the development and evolution of the mammalian brain. The EMBO journal 112 9843484
2014 Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency. Cell reports 108 24931607
2010 Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP. Nature neuroscience 104 21057506
2009 OTX2 is critical for the maintenance and progression of Shh-independent medulloblastomas. Cancer research 96 20028867
2013 The transcription factor Otx2 regulates choroid plexus development and function. Development (Cambridge, England) 95 23364326
2000 The subcellular localization of Otx2 is cell-type specific and developmentally regulated in the mouse retina. Brain research. Molecular brain research 90 10891582
2008 Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression. Proceedings of the National Academy of Sciences of the United States of America 85 18385377
1997 Cooperation between Otx1 and Otx2 genes in developmental patterning of rostral brain. Mechanisms of development 85 9486536
2015 Lhx1 functions together with Otx2, Foxa2, and Ldb1 to govern anterior mesendoderm, node, and midline development. Genes & development 84 26494787
2011 OTX2 microphthalmia syndrome: four novel mutations and delineation of a phenotype. Clinical genetics 81 20486942
2005 Emx2 and Pax6 function in cooperation with Otx2 and Otx1 to develop caudal forebrain primordium that includes future archipallium. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 15917450
2011 OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells. International journal of cancer 78 21964830
1999 Functional equivalency between Otx2 and Otx1 in development of the rostral head. Development (Cambridge, England) 78 9895322
1999 The TINS Lecture. Understanding the roles of Otx1 and Otx2 in the control of brain morphogenesis. Trends in neurosciences 76 10199636
1999 Fgf8 and Gbx2 induction concomitant with Otx2 repression is correlated with midbrain-hindbrain fate of caudal prosencephalon. Development (Cambridge, England) 76 10375509
1997 Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells. Development (Cambridge, England) 75 9374391
2007 Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification. Development (Cambridge, England) 74 18057103
2000 The Otx2 homeoprotein regulates expression from the gonadotropin-releasing hormone proximal promoter. Molecular endocrinology (Baltimore, Md.) 71 10935548
1999 Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes. Development (Cambridge, England) 69 10068635
2006 OTX1 and OTX2 expression correlates with the clinicopathologic classification of medulloblastomas. Journal of neuropathology and experimental neurology 66 16462208
2003 Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for vertebrate head specification. Development (Cambridge, England) 66 14645121
2001 Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast. Developmental biology 66 11412024
2000 Pax2, Otx2, Gbx2 and Fgf8 expression in early otic vesicle development. Mechanisms of development 63 10906468
2013 Loss of Otx2 in the adult retina disrupts retinal pigment epithelium function, causing photoreceptor degeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 61 23761884
2010 Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 59 20354145
2002 Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice. Development (Cambridge, England) 58 12183386
2007 Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon. Development (Cambridge, England) 57 17670791
2007 A new GFP-tagged line reveals unexpected Otx2 protein localization in retinal photoreceptors. BMC developmental biology 57 17980036
2005 Specification of the meso-isthmo-cerebellar region: the Otx2/Gbx2 boundary. Brain research. Brain research reviews 57 16111544
2011 Identification of a retina-specific Otx2 enhancer element active in immature developing photoreceptors. Developmental biology 56 21963459
2000 OTX2 directly interacts with LIM1 and HNF-3beta. Biochemical and biophysical research communications 55 10623575
2006 Otx2 controls identity and fate of glutamatergic progenitors of the thalamus by repressing GABAergic differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 16738237
2004 Otx2 homeobox gene induces photoreceptor-specific phenotypes in cells derived from adult iris and ciliary tissue. Investigative ophthalmology & visual science 53 15557469
2009 From brain formation to plasticity: insights on Otx2 homeoprotein. Development, growth & differentiation 51 19298552
2006 Temporal and spatial delineation of mouse Otx2 functions by conditional self-knockout. EMBO reports 51 16845372
2014 Otx2 ChIP-seq reveals unique and redundant functions in the mature mouse retina. PloS one 49 24558479
2010 Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration. PloS one 49 20657788
2007 Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat. Experimental eye research 49 17467693
2006 Molecular dissection reveals decreased activity and not dominant negative effect in human OTX2 mutants. Journal of molecular medicine (Berlin, Germany) 49 16607563
2020 Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells. The Journal of clinical investigation 46 31845906
2018 Methylation in OTX2 and related genes, maltreatment, and depression in children. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 44 30089883
2010 SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. The Journal of biological chemistry 44 20530484
2014 Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification. Nature communications 43 25005894
2004 Involvement of Pax6 and Otx2 in the forebrain-specific regulation of the vertebrate homeobox gene ANF/Hesx1. Developmental biology 42 15110720
2000 Coincidence of otx2 and BMP4 signaling correlates with Xenopus cement gland formation. Mechanisms of development 42 10727860
2016 Activated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX2 expression via TNF-α. Aging cell 41 27660103
2012 MiR-206 regulates neural cells proliferation and apoptosis via Otx2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 41 22508046
2006 Gbx2 and Otx2 interact with the WD40 domain of Groucho/Tle corepressors. Molecular and cellular biology 41 17060451
2011 Deletion of Otx2 in GnRH neurons results in a mouse model of hypogonadotropic hypogonadism. Molecular endocrinology (Baltimore, Md.) 40 21436260
2014 Deletion of OTX2 in neural ectoderm delays anterior pituitary development. Human molecular genetics 39 25315894
2012 OTX2 sustains a bivalent-like state of OTX2-bound promoters in medulloblastoma by maintaining their H3K27me3 levels. Acta neuropathologica 39 23179372
1999 Binding properties of the human homeodomain protein OTX2 to a DNA target sequence. FEBS letters 39 10069392
2017 Nitric oxide regulates homeoprotein OTX1 and OTX2 expression in the rat myenteric plexus after intestinal ischemia-reperfusion injury. American journal of physiology. Gastrointestinal and liver physiology 36 28154013
2020 OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification. eLife 35 32347797
2019 Non-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b/g. Cerebral cortex (New York, N.Y. : 1991) 35 29771284
2009 Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 35 19414065
2013 Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes. Human molecular genetics 34 24234651
2012 A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve. European journal of endocrinology 34 22715480
2012 OTX2 represses myogenic and neuronal differentiation in medulloblastoma cells. Cancer research 34 22986744
2001 Downstream of Otx2, or how to get a head. Trends in genetics : TIG 34 11672863
2017 OTX2 expression contributes to proliferation and progression in Myc-amplified medulloblastoma. American journal of cancer research 33 28401018
1997 The human homeodomain protein OTX2 binds to the human tenascin-C promoter and trans-represses its activity in transfected cells. DNA and cell biology 33 9174161
2010 The role of otx2 in adult mesencephalic-diencephalic dopaminergic neurons. Molecular neurobiology 32 21086067
2007 Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia. European journal of human genetics : EJHG 30 17406642
2002 Gbx2 interacts with Otx2 and patterns the anterior-posterior axis during gastrulation in Xenopus. Mechanisms of development 30 11850185
2014 Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm. Development (Cambridge, England) 29 25231759
2001 otx2 expression in the ectoderm activates anterior neural determination and is required for Xenopus cement gland formation. Developmental biology 29 11784058
2018 Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition. Brain : a journal of neurology 28 29490009
2012 Otx2 is involved in the regional specification of the developing retinal pigment epithelium by preventing the expression of sox2 and fgf8, factors that induce neural retina differentiation. PloS one 28 23145006
2010 Ectopic Mitf in the embryonic chick retina by co-transfection of β-catenin and Otx2. Investigative ophthalmology & visual science 28 20463321
2007 Acetylated YY1 regulates Otx2 expression in anterior neuroectoderm at two cis-sites 90 kb apart. The EMBO journal 28 17332747
2017 Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of Heterogeneous Identities in Embryonic Stem Cells. Stem cell reports 27 29056334
2015 Thyroid Hormone-Otx2 Signaling Is Required for Embryonic Ventral Midbrain Neural Stem Cells Differentiated into Dopamine Neurons. Stem cells and development 27 25867707
2021 The phenotypic spectrum associated with OTX2 mutations in humans. European journal of endocrinology 26 33950863
2020 An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate. Nature communications 26 32686664
2022 Brevican, Neurocan, Tenascin-C, and Tenascin-R Act as Important Regulators of the Interplay Between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons, and Otx2. Frontiers in cell and developmental biology 25 35721494
2016 Hmga2 is necessary for Otx2-dependent exit of embryonic stem cells from the pluripotent ground state. BMC biology 25 27036552
2013 Gene dosage of Otx2 is important for fertility in male mice. Molecular and cellular endocrinology 25 23811236
2005 Downregulation of Otx2 in the dedifferentiated RPE cells of regenerating newt retina. Brain research. Developmental brain research 25 15763275
2012 Gbx2 directly restricts Otx2 expression to forebrain and midbrain, competing with class III POU factors. Molecular and cellular biology 24 22566684
2010 Otx2 and Otx1 protect diencephalon and mesencephalon from caudalization into metencephalon during early brain regionalization. Developmental biology 23 20816794