Affinage

TLX3

T-cell leukemia homeobox protein 3 · UniProt O43711

Length
291 aa
Mass
31.9 kDa
Annotated
2026-06-10
48 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLX3 (RNX/HOX11L2) is a homeodomain transcription factor that acts as a post-mitotic selector gene specifying excitatory over inhibitory neuronal fate: it directly activates glutamatergic (dILB) differentiation genes and directly represses GABAergic (dILA) fate genes in the dorsal spinal cord, as established by reciprocal loss/gain-of-function and genome-wide ChIP-seq with in vivo null validation (PMID:15064766, PMID:33996801). Genetically it opposes the pro-GABAergic factor Lbx1, since Tlx3/Lbx1 double mutants restore glutamatergic differentiation lost in Tlx3 nulls (PMID:16234809). This selector function depends on direct DNA binding through a defined motif and on the homeodomain, which mediates interaction with the co-activator CBP in a manner enhanced by the TALE-class protein Pbx3 only after neural commitment (PMID:25428367, PMID:26258652); distinct N- and C-terminal domains partition transcriptional activation across target promoters (PMID:25138281). Beyond fate choice, TLX3 is required across the developing nervous system for the ventral medullary respiratory center (PMID:10700185), brainstem relay visceral and somatic sensory neurons and (nor)adrenergic centers derived from Mash1+/Phox2+ precursors (PMID:11581159, PMID:12023301), dorsal-horn peptidergic pain-modulatory neurons (PMID:18400903), DRG nociceptor/thermoceptor/pruriceptor specification in combination with Runx1 (PMID:22787056), sympathetic cholinergic phenotype acquisition (PMID:23804090), and cerebellar granule neuron progenitor proliferation (PMID:39628587). Its own transcription is gated by multiple inputs: basal expression by NFY binding tandem CCAAT boxes (PMID:16966433), induction by canonical Wnt/TCF and by Pax6 in cerebellum (PMID:21374761, PMID:27452274), a BMP/Cash1 cascade in brainstem (PMID:15922575), activity-dependent calcium/cJun signaling through a promoter CRE (PMID:20581840), and Notch-effector Hes-1 repression (PMID:21744064). In T-cell acute lymphoblastic leukemia, the t(5;14) translocation drives ectopic TLX3 expression via long-range BCL11B 3' enhancers regulated by PU.1 and HMGA1 (PMID:17308084, PMID:16926283), whereupon TLX3 transactivates LINC00478 to produce oncogenic miR-125b and arrest T-cell differentiation (PMID:29296717), represses the tumor-suppressive corepressor TLE4 (PMID:39838044), and cooperates with PHF6 loss and FLT3-ITD to drive leukemogenesis (PMID:30755422, PMID:39838044).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established the first physiological requirement for Tlx3, showing it is essential for a specific neural circuit rather than broadly dispensable.

    Evidence Rnx/Tlx3 knockout mouse with electrophysiology of medulla-spinal cord preparation

    PMID:10700185

    Open questions at the time
    • Did not define the transcriptional targets underlying respiratory neuron defect
    • No DNA-binding or partner mechanism identified
  2. 2002 High

    Resolved which neuronal classes depend on Tlx3 by defining its requirement in relay somatic and visceral sensory neurons and (nor)adrenergic centers from Mash1+ precursors.

    Evidence Single and double Rnx/Tlx-1 knockout mice with marker analysis, axonal tracing, and Phox2b epistasis

    PMID:11581159 PMID:12023301

    Open questions at the time
    • Direct target genes not identified
    • Whether Tlx3 acts as activator or repressor unresolved at this stage
  3. 2004 High

    Defined the core mechanistic identity of Tlx3 as a post-mitotic selector controlling the glutamatergic-versus-GABAergic fate switch, the central organizing principle of its neural function.

    Evidence Reciprocal knockout and ectopic overexpression in mouse/chick spinal cord with neurotransmitter marker readouts

    PMID:15064766

    Open questions at the time
    • Direct vs. indirect target regulation not distinguished
    • DNA motif and cofactors unknown
  4. 2005 High

    Placed Tlx3 in a genetic hierarchy by showing it acts in opposition to Lbx1, clarifying how excitatory fate overrides the default inhibitory program.

    Evidence Tlx3/Lbx1 double-knockout epistasis with marker analysis

    PMID:16234809

    Open questions at the time
    • Molecular nature of Tlx3-Lbx1 antagonism (competition vs. independent targets) unresolved
  5. 2006 High

    Identified the first transcriptional driver of TLX3 itself, establishing NFY as the basal promoter activator.

    Evidence Reporter assays, CCAAT-box mutagenesis, ChIP, EMSA, dominant-negative and siRNA NFY in cell lines

    PMID:16966433

    Open questions at the time
    • Tissue-specific activators beyond basal NFY not addressed
    • Does not explain spatial restriction in vivo
  6. 2008 Medium

    Showed Tlx3 function is context-dependent, acting as a selector only after neural induction, explaining why ectopic expression has cell-state-specific effects.

    Evidence Stable Tlx3 expression in ES cells with neural induction and temporal gene expression profiling

    PMID:18391221

    Open questions at the time
    • Cofactor responsible for context dependence not identified here
    • Direct targets not mapped
  7. 2011 Medium

    Expanded the upstream regulatory network by identifying Wnt/TCF activation, BMP/Cash1 induction, and Notch/Hes-1 repression as inputs gating Tlx3 expression.

    Evidence ChIP for TCF3/4, chick BMP/Noggin gain/loss-of-function, and Hes-1 promoter-reporter/knockdown assays

    PMID:15922575 PMID:21374761 PMID:21744064

    Open questions at the time
    • Integration of these signals on the endogenous locus in vivo not shown
    • Quantitative contribution of each pathway unknown
  8. 2012 High

    Defined combinatorial logic in sensory neurons, showing Tlx3 cooperates with Runx1 to specify DRG nociceptor/pruriceptor identity and sensory channel repertoire.

    Evidence Conditional Tlx3 and Runx1 knockouts plus co-overexpression with sensory marker analysis

    PMID:22787056

    Open questions at the time
    • Whether Tlx3 and Runx1 co-bind shared enhancers not directly tested
  9. 2014 Medium

    Established the biochemical basis of Tlx3 action by defining its DNA-binding motif and the modular domains that drive activation of direct targets such as Prrxl1.

    Evidence Structure-based homology modeling with EMSA, plus promoter-reporter domain mutagenesis and in vivo epistasis

    PMID:25138281 PMID:25428367

    Open questions at the time
    • Genome-wide direct targets not yet defined
    • Structural model not experimentally solved
  10. 2015 Medium

    Identified the homeodomain-dependent recruitment of co-activator CBP, enhanced by Pbx3, as the cofactor mechanism enabling Tlx3 activation of glutamatergic genes.

    Evidence Reciprocal Co-IP, homeodomain mutagenesis, and ES cell neural differentiation with functional readout

    PMID:26258652

    Open questions at the time
    • Direct repression cofactor for GABAergic targets not identified
    • Single-lab interaction data
  11. 2021 High

    Provided genome-wide proof that Tlx3 acts directly as both activator of excitatory genes and repressor of inhibitory genes, consolidating its dual selector mechanism.

    Evidence ChIP-seq plus transcriptome profiling in Tlx3-null mouse dorsal spinal cord

    PMID:33996801

    Open questions at the time
    • Repression cofactors at directly repressed loci not defined
    • Chromatin context of bound sites not characterized
  12. 2025 Medium

    Defined the oncogenic mechanism of ectopic TLX3 in T-ALL, from enhancer-driven activation to its downstream transcriptional program and cooperating lesions.

    Evidence Enhancer mapping/DNase mapping, ChIP, miRNA profiling, ex vivo pro-T cell models with FLT3-ITD/TLE4, and Phf6-loss cooperation in mice

    PMID:16926283 PMID:17308084 PMID:29296717 PMID:30755422 PMID:39838044

    Open questions at the time
    • Direct TLX3 oncogenic target gene set incompletely defined
    • Most rescue/cooperation experiments from single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how TLX3 mechanistically switches between activation and repression at individual loci and how its dual neural-selector activity relates to its leukemogenic transcriptional program.
  • No experimentally solved TLX3-DNA structure
  • Repression-specific cofactors not identified
  • Reported TLX3-STAT3 interaction in HCC rests on a single non-reciprocal Co-IP

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 3
Partners
BRN3ACBPPBX3RUNX1STAT3TLE4

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Tlx3 (and Tlx1) are post-mitotic selector genes that determine glutamatergic over GABAergic cell fates in the mouse dorsal spinal cord. Loss of Tlx3 results in absence of glutamatergic markers (VGLUT2, Gria2) and derepression of GABAergic markers (Pax2, Gad1/2, Viaat, Grik2/3); ectopic Tlx3 expression is sufficient to suppress GABAergic differentiation and induce glutamatergic neurons. Knockout mouse (loss-of-function), ectopic overexpression in chick spinal cord, in situ hybridization for neurotransmitter markers Nature neuroscience High 15064766
2005 Tlx3 acts to antagonize Lbx1 to promote glutamatergic differentiation: in Tlx3−/−Lbx1−/− double mutants, the impaired glutamatergic differentiation observed in Tlx3−/− mice is restored, placing Tlx3 genetically downstream of or in opposition to Lbx1. Genetic epistasis analysis using Tlx3−/−, Lbx1−/−, and Tlx3−/−Lbx1−/− double-knockout mice; marker analysis by in situ hybridization Nature neuroscience High 16234809
2000 Rnx/Tlx3 is required for development of the ventral medullary respiratory centre; Rnx-deficient mice die within 24 hours of birth from central respiratory failure, with abnormal inspiratory neuron activity in the ventrolateral medulla. Gene knockout in mouse ES cells; electromyographic and electrophysiological analysis of medulla-spinal cord preparation Nature genetics High 10700185
2001 Rnx/Tlx3 is required for formation of first-order relay visceral sensory neurons in the brainstem and for development of most (nor)adrenergic centers; these neurons derive from Mash1-positive precursors co-expressing Rnx and Phox2 proteins. Genetic evidence indicates Rnx and Phox2 function independently to specify the (nor)adrenergic phenotype. Rnx-knockout mouse analysis; marker expression studies; genetic epistasis with Phox2b mutants Genes & development High 11581159
2002 Rnx/Tlx3 (together with Tlx-1) is required for proper formation of relay somatic sensory neurons (trigeminal nuclei and dorsal spinal cord D2/D4 interneurons) derived from Mash1-positive neural precursors; Rnx and Tlx-1 maintain expression of Drg11 and are essential for ingrowth of trkA+ nociceptive/thermoceptive sensory afferents to their central targets. Rnx and Tlx-1 single and double knockout mouse analysis; marker expression and axonal tracing Genes & development High 12023301
2008 Tlx3 and Tlx1 coordinate specification of dorsal horn pain-modulatory peptidergic neurons: Tlx3+ neurons represent a heterogeneous population expressing cholecystokinin, Substance P, Neurokinin B, and somatostatin. Mutations of Tlx3 and Tlx1 result in loss of these peptide genes. Brn3a, partly dependent on Tlx3, is required specifically for early Substance P expression. Genetic fate mapping of Tlx3+ neurons; Tlx3 and Tlx1 knockout mouse analysis; in situ hybridization and immunostaining for neuropeptide markers The Journal of neuroscience High 18400903
2010 In Xenopus tropicalis dorsal spinal cord neurons, calcium spike activity modulates tlx3 transcription through a variant cAMP response element (CRE) in its promoter. The transcription factor cJun binds this CRE site and regulates neurotransmitter phenotype via its transactivation domain; calcium signals through cJun N-terminal phosphorylation to integrate activity-dependent and intrinsic neurotransmitter specification via tlx3. Promoter reporter assays; ChIP for cJun binding to the tlx3 CRE; dominant-negative and phosphorylation-site mutant cJun constructs; calcium imaging and manipulation in Xenopus embryos Nature neuroscience High 20581840
2011 Wnt1/β-catenin signaling upregulates Tlx3 expression in mesenchymal stem cells (MSCs) undergoing neural induction. TCF3/4 (Wnt-activated DNA-binding proteins) bind a regulatory region of the Tlx3 gene as shown by chromatin immunoprecipitation. Forced expression of Tlx3 in MSCs induces sensory and glutamatergic neuron markers, placing Tlx3 as a direct transcriptional target of canonical Wnt signaling. ChIP assay for TCF3/4 binding to Tlx3 regulatory region; canonical Wnt inhibitor suppression of Tlx3 expression; forced Tlx3 expression in MSCs with neural induction Stem cells (Dayton, Ohio) Medium 21374761
2005 A BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing brainstem. BMP receptor Bmpr-1b expression correlates with Tlx-3; BMP gain-of-function combined with Mash1 overexpression induces Tlx-3 expression in vivo; Noggin misexpression increases Tlx-3+ neurons. In vivo rhombomere inversion; electroporation of BMP/Noggin/Mash1 expression vectors in chick embryo; in situ hybridization Mechanisms of development Medium 15922575
2011 The Notch target gene Hes-1 negatively regulates Tlx3 expression: Hes-1 represses the Tlx3 promoter via WRPW domain-mediated co-repressor recruitment, and downregulation of Hes-1 relieves this inhibition to promote glutamatergic differentiation. Promoter-reporter transfection assays with truncated/mutated Hes-1 constructs; Hes-1 knockdown; Tlx3 mRNA quantification Cellular and molecular life sciences Medium 21744064
2006 Nuclear factor Y (NFY) drives basal transcription of TLX3 by binding two tandem CCAAT boxes in the 5'-UTR/proximal promoter region. Dominant-negative NFY, NFY knockdown, ChIP, and EMSA all confirm this interaction; NFY binding is required for basal TLX3 promoter activity and endogenous TLX3 mRNA levels. In vitro transfection reporter assays; site-directed mutagenesis of CCAAT boxes; ChIP; EMSA; dominant-negative NFY; NFY siRNA knockdown Molecular cancer research High 16966433
2014 TLX3 DNA-binding specificity was determined by structure-based homology modeling and confirmed by gel-shift (EMSA) assay; TLX3 binds specific DNA motifs enriched in promoters of genes related to hematopoiesis and tissue morphology. Computational homology modeling (TF2DNA); gel-shift (EMSA) assay validation of predicted binding motif Nucleic acids research Medium 25428367
2015 Tlx3 directly interacts with the epigenetic co-activator CBP (CREB-binding protein); the Tlx3 homeodomain is essential for this interaction. The interaction is enhanced by the TALE-class homeodomain protein Pbx3 and becomes detectable only after ES cells are committed to a neural lineage coinciding with increased Pbx3 expression. Mutant Tlx3 lacking the homeodomain shows significantly reduced glutamatergic neuronal subtype marker expression. Co-immunoprecipitation; domain-deletion/mutagenesis of Tlx3 homeodomain; ES cell neural differentiation model; gene expression analysis PloS one Medium 26258652
2012 Tlx3 acts in combination with Runx1 to control the development of DRG nociceptors, thermoceptors, and pruriceptors: Tlx3 is required to establish most Runx1-dependent phenotypes (TrkA vs. Ret neuron segregation; expression of ~12 sensory channels/receptors). Tlx3 and Runx1 expression is independent at prenatal stages, and co-overexpression of both induces ectopic sensory channels/receptors. Conditional Tlx3 knockout in DRG; Runx1 knockout comparison; co-overexpression of Runx1+Tlx3; in situ hybridization and immunostaining for sensory markers The Journal of neuroscience High 22787056
2013 Tlx3 is required for cholinergic phenotype acquisition in prenatal sympathetic neurons: deletion of Tlx3 results in loss of VAChT expression at E18.5, and loss of cholinergic peptides VIP and somatostatin at both E12.5 and E18.5. Tlx3 also maintains high-level Ret expression in these neurons. Tlx3 conditional knockout mouse; immunostaining and in situ hybridization for VAChT, VIP, somatostatin, Ret, TH The Journal of neuroscience High 23804090
2014 Tlx3 activates the Prrxl1 TATA-containing P3 promoter by directly binding a bipartite DNA motif; Tlx3 also indirectly activates Prrxl1 TATA-less P1/P2 promoters via Brn3a. The Tlx3 N-terminal domain (1–38) is critical for overall transcriptional activity; the C-terminus (256–291) mediates P1/P2 activation; domain 76–111 decreases P3 activity. Additionally, Tlx3 promotes Prrxl1 hyperphosphorylation via its 76–111 domain. Promoter-reporter transfection assays with Tlx3 domain deletion/truncation mutants; EMSA for direct DNA binding; epistatic analysis in Tlx3 mutant mice Biochimica et biophysica acta Medium 25138281
2016 Pax6 is a key transcriptional activator of Tlx3 specifically in the cerebellum; Pax6−/− mice show loss of Tlx3 expression in cerebellar granule neuron progenitors. Tlx3 in turn is required for restricted expression of the nicotinic cholinergic receptor α3 subunit (Chrnα3) in cerebellar granule neurons. Pax6−/− (Sey) mouse model; in situ hybridization and molecular interaction studies; in vivo Chrnα3 expression analysis in Tlx3 conditional context Scientific reports Medium 27452274
2017 TLX3 directly regulates miR-125b production in T-ALL through binding and transactivating LINC00478 (the host lncRNA of miR-99a/Let-7c/miR-125b); TLX3-driven miR-125b suppresses Ets1 and CBFβ to promote T-cell differentiation arrest. Loss- and gain-of-function experiments confirm TLX3 supports in vitro cell growth and in vivo invasiveness of T-ALL. Loss- and gain-of-function (shRNA knockdown, ectopic expression); ChIP for TLX3 binding to LINC00478 locus; miRNA expression profiling; xenograft in vivo model Blood advances Medium 29296717
2019 Loss of PHF6 and ectopic TLX3 expression cooperate to cause fully penetrant early-onset leukemia in mice; TLX3 expression alone causes only partially penetrant leukemia, demonstrating cooperative oncogenesis. Conditional Phf6 knockout mouse combined with retroviral TLX3 expression; serial transplantation; leukemia incidence assessment Blood Medium 30755422
2019 TLX3 attenuates EMT in hepatocellular carcinoma by binding directly to STAT3 and inhibiting STAT3 phosphorylation, thereby downregulating SNAI1 expression and reversing the IL-6/STAT3/SNAI1 signaling axis. Co-immunoprecipitation (TLX3-STAT3 interaction); overexpression and knockdown of TLX3; gene expression microarray; in vivo xenograft International journal of biological sciences Low 31360112
2021 ChIP-seq combined with expression profiling in Tlx3-null mouse embryonic dorsal spinal cord reveals that Tlx3 directly activates most dILB (glutamatergic) neuron-specific genes and directly represses many genes associated with the alternative inhibitory dILA (GABAergic) neuronal fate, including transcription factors and terminal differentiation genes. ChIP-seq in mouse embryonic dorsal spinal cord; transcriptome profiling; validation in Tlx3 null embryos Frontiers in cell and developmental biology High 33996801
2021 HAp nanorod-induced elevation of intracellular calcium activates c-Jun, which suppresses TLX3 expression, thereby promoting GABAergic over glutamatergic neurogenesis from neural stem cells — mechanistically consistent with the known role of c-Jun/TLX3 signaling in neurotransmitter fate specification. Calcium imaging; c-Jun activation assays; TLX3 expression analysis; neural stem cell differentiation assay with HAp nanorods Nano letters Low 34423634
2007 TLX3 ectopic expression in t(5;14) T-ALL is driven by remote BCL11B 3' enhancers; PU.1 and HMGA1 co-regulate TLX3 expression via interactions at these enhancers/nuclear matrix. Knockdown of PU.1 or HMGA1 downregulates TLX3, and candidate enhancers are hyperacetylated; TLX3 promoter/exon 1 are hypoacetylated but expression is trichostatin A sensitive. DNA inhibitory oligonucleotide treatment targeting candidate enhancers; ChIP for histone acetylation; PU.1 and HMGA1 siRNA knockdown; genomic analysis of enhancer binding sites Cancer research Medium 17308084
2006 t(5;14)(q35;q32) juxtaposes TLX3 with long-range cis-activating regulatory regions downstream of BCL11B that are active during T-cell differentiation. DNase I hypersensitive site mapping identified two such regions that have cis-activation properties in T cells and can activate the TLX3 promoter in transient transfection experiments. DNase I hypersensitivity mapping; transient transfection reporter assays in T cells; breakpoint sequencing in 8 t(5;14) patients Blood Medium 16926283
2025 TLX3 directly represses TLE4 expression in T-ALL; TLE4 acts as a repressor of TLX3 oncogenic activity. Co-expression of TLX3 and FLT3-ITD in ex vivo pro-T cells confers IL7-independent growth, and TLE4 re-expression partially reverses the TLX3 transcriptional program in this model. Ex vivo pro-T cell model with retroviral TLX3 and FLT3-ITD co-expression; gene expression profiling; TLE4 forced expression; patient T-ALL gene expression data Leukemia Medium 39838044
2024 Tlx3 dysfunction in cerebellar granule neuron progenitors (GNPs) reduces their proliferation by regulating anti-proliferative genes, leading to cerebellar hypoplasia, patterning defects, granule neuron-Purkinje ratio imbalance, and autism-like behavior in mice. Conditional Tlx3 knockout specifically in GNPs; ChIP-seq/RNA-seq; behavioral testing; in situ hybridization for proliferation and patterning markers iScience Medium 39628587
2024 Tlx3 is expressed in neural crest-derived cells contributing to the chick trigeminal ganglion; loss of Tlx3 function diminishes ganglion size and neuron abundance, while ectopic Tlx3 expression in migrating cranial neural crest causes premature neuronal differentiation. Lineage labeling combined with in situ hybridization in chick; in vivo Tlx3 loss-of-function (morpholino/CRISPR); ectopic Tlx3 electroporation in migrating neural crest Developmental biology Medium 39019425
2008 Tlx3 exerts context-dependent transcriptional regulation: in undifferentiated ES cells, Tlx3 overexpression has no significant effect on gene expression; after neural induction, Tlx3 promotes sequential expression of proneural genes (Mash1, Ngn1, NeuroD) followed by glutamatergic markers (VGLUT2, GluR2, GluR4), functioning as a selector gene in a neural differentiation context. Stable transfection of Tlx3 in mouse ES cells; neural induction; gene expression analysis at multiple time points PNAS Medium 18391221

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nature neuroscience 291 15064766
2001 A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia 180 11587205
2005 Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes. Nature neuroscience 157 16234809
2000 Rnx deficiency results in congenital central hypoventilation. Nature genetics 127 10700185
2001 Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3. Genes & development 109 11581159
2003 Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951. Blood 98 14504110
2002 Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Genes & development 96 12023301
2011 Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx3. Stem cells (Dayton, Ohio) 76 21374761
2014 Prediction of DNA binding motifs from 3D models of transcription factors; identifying TLX3 regulated genes. Nucleic acids research 73 25428367
2010 cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification. Nature neuroscience 70 20581840
2007 Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1. Cancer research 67 17308084
2008 Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 65 18400903
2003 t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH). Leukemia 50 12970786
2003 Activation of HOX11L2 by juxtaposition with 3'-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2). Genes, chromosomes & cancer 46 12661009
2019 PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia. Blood 45 30755422
2006 HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32). Blood 41 16926283
2004 Various types of rearrangements target TLX3 locus in T-cell acute lymphoblastic leukemia. Genes, chromosomes & cancer 40 15334547
2002 Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11). Leukemia 37 12399963
2012 Tlx3 and Runx1 act in combination to coordinate the development of a cohort of nociceptors, thermoceptors, and pruriceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 34 22787056
2008 Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 33 18391221
2002 High incidence of Hox11L2 expression in children with T-ALL. Leukemia 31 12454747
2017 Homeobox protein TLX3 activates miR-125b expression to promote T-cell acute lymphoblastic leukemia. Blood advances 29 29296717
2008 Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group. Leukemia 29 18368072
2006 Transforming potential of the T-cell acute lymphoblastic leukemia-associated homeobox genes HOXA13, TLX1, and TLX3. Genes, chromosomes & cancer 29 16804919
2008 Cooperative genetic defects in TLX3 rearranged pediatric T-ALL. Leukemia 24 18185524
2016 Regulation of Tlx3 by Pax6 is required for the restricted expression of Chrnα3 in Cerebellar Granule Neuron progenitors during development. Scientific reports 16 27452274
2013 Tlx3 controls cholinergic transmitter and Peptide phenotypes in a subset of prenatal sympathetic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 23804090
2005 A BMP-mediated transcriptional cascade involving Cash1 and Tlx-3 specifies first-order relay sensory neurons in the developing hindbrain. Mechanisms of development 16 15922575
2021 Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods. Nano letters 15 34423634
2002 Mutational analysis of the RNX gene in congenital central hypoventilation syndrome. American journal of medical genetics 15 12407709
2015 Tlx3 promotes glutamatergic neuronal subtype specification through direct interactions with the chromatin modifier CBP. PloS one 13 26258652
2011 Hes-1 regulates the excitatory fate of neural progenitors through modulation of Tlx3 (HOX11L2) expression. Cellular and molecular life sciences : CMLS 13 21744064
2003 Exclusion of RNX as a major gene in congenital central hypoventilation syndrome (CCHS, Ondine's curse). American journal of medical genetics. Part A 13 12548735
2002 Onset of Tlx-3 expression in the chick cerebellar cortex correlates with the morphological development of fissures and delineates a posterior transverse boundary. The Journal of comparative neurology 13 12012426
2006 Nuclear factor Y drives basal transcription of the human TLX3, a gene overexpressed in T-cell acute lymphocytic leukemia. Molecular cancer research : MCR 12 16966433
2004 Two dual-color split signal fluorescence in situ hybridization assays to detect t(5;14) involving HOX11L2 or CSX in T-cell acute lymphoblastic leukemia. Haematologica 12 15194534
2017 Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations. Frontiers in molecular neuroscience 10 28701920
2019 TLX3 repressed SNAI1-induced epithelial-mesenchymal transition by directly constraining STAT3 phosphorylation and functionally sensitized 5-FU chemotherapy in hepatocellular carcinoma. International journal of biological sciences 9 31360112
2021 Tlx3 Exerts Direct Control in Specifying Excitatory Over Inhibitory Neurons in the Dorsal Spinal Cord. Frontiers in cell and developmental biology 8 33996801
2015 Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia. Blood cells, molecules & diseases 5 26852660
2013 NKX2-5, SIL/TAL and TLX3/HOX11L2 expression in Egyptian pediatric T-cell acute lymphoblastic leukemia. Asia-Pacific journal of clinical oncology 4 24571118
2024 T/myeloid mixed phenotype acute leukaemia harbouring TLX3::BCL11B with TLX3 activation. British journal of haematology 3 38385580
2014 Dual role of Tlx3 as modulator of Prrxl1 transcription and phosphorylation. Biochimica et biophysica acta 3 25138281
2024 Tlx3 mediates neuronal differentiation and proper condensation of the developing trigeminal ganglion. Developmental biology 2 39019425
2024 TLX3 regulates CGN progenitor proliferation during cerebellum development and its dysfunction can lead to autism. iScience 2 39628587
2025 TLE4 is a repressor of the oncogenic activity of TLX3 in T-cell acute lymphoblastic leukemia. Leukemia 1 39838044
2022 Tlx3 controls the development of C-low threshold mechanoreceptors. Neuroreport 1 36062515
2005 [HOX11L2 expression and its clinical significance in paraffin-embedded T-lymphoblastic lymphoma]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 0 16532965

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