Affinage

DLX1

Homeobox protein DLX-1 · UniProt P56177

Length
255 aa
Mass
27.3 kDa
Annotated
2026-06-09
64 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLX1 is a nuclear homeodomain transcription factor that governs cell-fate decisions in the developing forebrain, where it specifies the differentiation and survival of GABAergic interneurons and striatal neurons while restraining alternative fates (PMID:9247261, PMID:16007083, PMID:17678855). Acting together with its paralog DLX2, it directs late-born striatal matrix and subventricular-zone neurons through differentiation (PMID:9247261), specifies cortical and hippocampal interneuron subtypes, and is required cell-autonomously for postnatal survival of calretinin+ and somatostatin+ (but not parvalbumin+) interneurons, whose loss reduces inhibitory transmission and produces delayed-onset epilepsy (PMID:16007083). Mechanistically, DLX1 functions as both an activator and a repressor: it directly activates GABAergic identity genes (Gad1, Gad2, Vgat) and lineage determinants including Brn3b, Meis2, and Zfhx1b (PMID:29028947, PMID:28356311, PMID:35156680, PMID:23312518), while repressing oligodendroglial and alternative neuronal programs—repressing OPC formation (PMID:17678855), directly binding and repressing Otp to suppress AgRP fate (PMID:29795232), and decommissioning enhancers near repressed genes such as Olig2 through a motif that recruits the NuRD chromatin remodeling complex via RBBP4 (PMID:35695185). It also assembles into an Evf2 lncRNA-containing ribonucleoprotein complex with the remodeler BRG1 at enhancers, where the RNA inhibits BRG1 ATPase activity to convert active enhancers to a repressed state (PMID:26138476). DLX1 expression is itself directly activated by MASH1 and DLX autoregulation through the I12b intergenic enhancer (PMID:17409112), and repressed by Olig1 and by Rb/E2F factors acting at the same locus (PMID:24507192, PMID:22699903). Beyond neural development, DLX1 patterns the branchial arches and confers odontogenic competence on cranial-neural-crest ectomesenchyme (PMID:9187081, PMID:9428417), and is required for enteric nervous system motility via VIP-lineage neurons (PMID:32017713). In cancer, DLX1 physically interacts with SMAD4 to modulate TGF-β superfamily signaling (PMID:14671321, PMID:27593933) and drives a DLX1–NCS1–MYC transcriptional axis (PMID:40614386).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1997 High

    Established that Dlx1/2 are required for neuronal differentiation in the developing basal ganglia, defining the genes' core role in forebrain neurogenesis.

    Evidence Dlx1/Dlx2 double-null mice with histological and marker analysis of striatum and SVZ

    PMID:9247261

    Open questions at the time
    • Does not identify direct transcriptional targets
    • Single vs double knockout contributions to differentiation not fully separated
  2. 1997 High

    Showed Dlx1/2 control proximodistal patterning of the branchial arches and confer odontogenic competence on cranial neural crest, extending function beyond the CNS to craniofacial development.

    Evidence Single and double knockout mice plus heterologous epithelial-mesenchymal tissue recombination with Barx1/Sox9 markers

    PMID:9187081 PMID:9428417

    Open questions at the time
    • Direct DLX1 target genes in ectomesenchyme not identified
    • Molecular basis of the chondrogenic transfate unresolved
  3. 1999 Medium

    Determined that DLX1/2 are nuclear proteins partitioned symmetrically at mitosis with a defined temporal expression order, anchoring their site of action and developmental sequence.

    Evidence Immunofluorescence and confocal microscopy in basal forebrain neurons

    PMID:10516593

    Open questions at the time
    • Does not address transcriptional mechanism
    • Functional consequence of symmetric inheritance unknown
  4. 2003 Medium

    Identified the first DLX1 protein partner, showing DLX1 binds SMAD4 through its homeodomain to block TGF-β superfamily signaling, linking a homeodomain factor to growth-factor signal inhibition.

    Evidence Co-IP, domain mapping, reporter and differentiation assays in hematopoietic cell lines

    PMID:14671321

    Open questions at the time
    • Co-IP not reciprocally validated in vivo
    • Physiological context of the interaction in development not tested
  5. 2005 High

    Demonstrated cell-autonomous requirement of Dlx1 for postnatal survival of specific interneuron subtypes, connecting the transcription factor to inhibitory circuit integrity and epilepsy.

    Evidence Dlx1 null mice, cell transplantation, IPSC recordings, and in vivo EEG

    PMID:16007083

    Open questions at the time
    • Survival target genes downstream of Dlx1 not defined
    • Why parvalbumin+ cells are spared unexplained
  6. 2007 High

    Defined the I12b enhancer as the regulatory hub for Dlx1/2, directly bound by MASH1 and by DLX proteins themselves, establishing both upstream proneural activation and autoregulation.

    Evidence DNase I footprinting, transgenic reporter and co-transfection assays with binding-site mutagenesis

    PMID:17409112

    Open questions at the time
    • Does not establish in vivo necessity of each binding site
    • Cofactors at I12b not identified
  7. 2007 High

    Showed Dlx1/2 actively repress oligodendrocyte fate, establishing a neuronal-versus-glial fate switch operating in a common progenitor.

    Evidence Dlx1/2 double knockout progenitor transplantation into wild-type mice with oligodendrocyte marker immunofluorescence

    PMID:17678855

    Open questions at the time
    • Direct repressed targets driving the switch not identified at this stage
    • Mechanism of repression unknown
  8. 2012 High

    Placed Dlx1/2 within the Rb/E2F regulatory network, with repressor E2Fs directly suppressing Dlx transcription at the I12b enhancer and promoter.

    Evidence ChIP (in vitro and in vivo), Rb knockout mice, luciferase reporter with E2F site mutations

    PMID:22699903

    Open questions at the time
    • Cell-cycle context coupling Rb/E2F to Dlx not fully defined
    • Does not address whether this operates in all interneuron lineages
  9. 2013 Medium

    Resolved the genetic order downstream of Dlx1/2, showing they activate Zfhx1b to repress Nkx2-1 and direct cortical over striatal interneuron identity.

    Evidence Conditional knockout mice with in situ hybridization, IHC and epistasis

    PMID:23312518

    Open questions at the time
    • Direct DLX1 binding to Zfhx1b not shown
    • Single lab
  10. 2013 Medium

    Connected Dlx1 to interneuron morphogenesis, showing DNA-binding-dependent suppression of dendritic complexity via neuropilin-2 and PAK3.

    Evidence Ectopic expression/knockdown in hippocampal cultures with morphometric and downstream-effector manipulation

    PMID:24236816

    Open questions at the time
    • Direct vs indirect regulation of neuropilin-2/PAK3 unresolved
    • In vivo relevance not tested
  11. 2014 High

    Identified Olig1 as a direct repressor of Dlx1/2 at the I12b enhancer, defining an Olig1-Dlx1/2 axis tuning cortical interneuron number.

    Evidence Olig1 knockout mice, ChIP for direct I12b binding, immunofluorescence and cell counting

    PMID:24507192

    Open questions at the time
    • Does not address combinatorial control with E2F at the same enhancer
    • Direct downstream consequences of de-repression not mapped
  12. 2015 High

    Revealed a chromatin-level mechanism in which DLX1 assembles with the Evf2 lncRNA and BRG1 at enhancers, where the RNA inhibits BRG1 remodeling to convert active enhancers to repressed states.

    Evidence Mass spectrometry, Co-IP, ChIP, and in vitro BRG1 ATPase and remodeling assays

    PMID:26138476

    Open questions at the time
    • Genome-wide DLX1-Evf2-BRG1 target set not fully defined
    • How DLX1 selects enhancers for this complex unknown
  13. 2017 High

    Established DLX1/2 as direct transcriptional activators of Brn3b in retinal ganglion cell progenitors, with synergistic genetic interaction underlying RGC formation.

    Evidence Triple-knockout mice, retinal knockdown, in utero gain-of-function, luciferase assays

    PMID:28356311

    Open questions at the time
    • Cofactors required for Brn3b activation not identified
    • Mechanism of greater-than-additive interaction unresolved
  14. 2018 High

    Demonstrated DLX2 directly drives GABAergic identity genes (Gad1, Gad2, Vgat) and that loss impairs inhibitory synapse formation, mechanistically linking DLX activity to GABAergic neurotransmission.

    Evidence Conditional knockouts, mIPSC recordings, ChIP/reporter assays, immunofluorescence

    PMID:29028947

    Open questions at the time
    • Relative contributions of Gad/Vgat vs GRIN2B to phenotype not separated
    • DLX1 vs DLX2 individual roles partly conflated
  15. 2018 High

    Extended Dlx1/2 fate control to the hypothalamus, where they specify GHRH identity and directly repress Otp to suppress AgRP fate, defining a Dlx1/2-Otp axis with metabolic consequences.

    Evidence Dlx1/2-deficient mice, ChIP for direct Otp binding, immunofluorescence, metabolic phenotyping

    PMID:29795232

    Open questions at the time
    • Repressive cofactors at Otp not identified
    • Generality of the axis across hypothalamic nuclei untested
  16. 2018 Medium

    Implicated DLX1 in cancer signaling, showing FOXM1-driven DLX1 promotes ovarian cancer aggressiveness through nuclear SMAD4 interaction, and FLT3/MAPK-driven DLX1 blunts TGF-β/Smad signaling in AML.

    Evidence Reporter assays, Co-IP, siRNA, xenografts (ovarian); pharmacological/siRNA FLT3 manipulation with RPPA (AML)

    PMID:21357706 PMID:27593933

    Open questions at the time
    • Direct DLX1 target genes mediating oncogenicity incompletely defined
    • SMAD4 interaction relies on Co-IP without structural validation
  17. 2018 Low

    Reported a DLX1-β-catenin interaction enhancing β-catenin/TCF4 signaling to promote prostate cancer growth, linking DLX1 to Wnt-pathway activation.

    Evidence Co-IP, reporter assays, ectopic expression, proliferation/migration assays

    PMID:29317218

    Open questions at the time
    • Single Co-IP without reciprocal or structural validation
    • In vivo relevance not tested
  18. 2019 Medium

    Showed Dlx1/2 are required for differentiation of GSX2+/ASCL1+ progenitors into olfactory bulb interneurons embryonically and postnatally, and are sufficient to induce ectopic OB-like interneurons partly via Sp8/9.

    Evidence Constitutive/conditional knockouts, in utero electroporation overexpression, compound mutant analysis

    PMID:30796806

    Open questions at the time
    • Direct DLX1 binding to Sp8/9 not shown
    • Single lab
  19. 2020 Medium

    Extended Dlx1/2 function to the enteric nervous system, where they are required for bowel motility and VIP-lineage neuron generation.

    Evidence Knockout mice, bowel motility assays, RNA-seq, reporter mice, IHC

    PMID:32017713

    Open questions at the time
    • Direct binding of Dlx1/2 to Vip not demonstrated
    • Single lab
  20. 2022 High

    Defined the molecular basis of DLX1-mediated repression, showing an RBBP4-binding motif recruits the NuRD complex to co-occupy and decommission enhancers near repressed genes including Olig2.

    Evidence Co-IP, ChIP-seq of DLX1 and six NuRD subunits, ATAC-seq, compound heterozygous mouse genetics

    PMID:35695185

    Open questions at the time
    • Whether NuRD recruitment occurs at all DLX1 repressed targets unknown
    • Interplay with the Evf2/BRG1 repressive mechanism not reconciled
  21. 2022 Medium

    Mapped a Dlx1/2 → Meis2 → Zfp503/Six3 pathway through the hs599 enhancer for striatal medium spiny neuron fate determination.

    Evidence Conditional knockouts, ChIP for Meis2 targets, hs599 enhancer reporter, immunofluorescence

    PMID:35156680

    Open questions at the time
    • Direct DLX1 binding to the Meis2/hs599 element not fully established
    • Single lab
  22. 2025 Medium

    Defined a DLX1-NCS1-MYC oncogenic axis in lung adenocarcinoma via direct DLX1 binding to the NCS1 promoter.

    Evidence ChIP, luciferase assays, RNA-seq, siRNA knockdown, in vivo xenograft

    PMID:40614386

    Open questions at the time
    • Single lab and single publication
    • Mechanism by which NCS1 regulates MYC not detailed
  23. 2025 Medium

    Linked DLX1 to neurodegeneration, showing its translation escapes PERK-B UPR suppression, its solubility shifts in PSP brain, and homolog silencing reduces tau toxicity.

    Evidence SUnSET proteomics, PERK haplotype comparison, detergent fractionation of human PSP tissue, Drosophila dll RNAi tau toxicity assay

    PMID:41708330

    Open questions at the time
    • Mechanism connecting DLX1 to tau pathology unresolved
    • Relies on fly homolog for in vivo rescue

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DLX1 switches between activator and repressor modes at distinct targets, and how its multiple repressive machineries (NuRD/RBBP4 vs Evf2/BRG1) are deployed and coordinated, remains unresolved.
  • No unified model of activator-vs-repressor target selection
  • Relationship between NuRD and Evf2/BRG1 repression mechanisms unknown
  • Structural basis of partner interactions (SMAD4, β-catenin, RBBP4, BRG1) undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0140096 catalytic activity, acting on a protein 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-4839726 Chromatin organization 2
Partners
BRG1 (SMARCA4)CTNNB1 (BETA-CATENIN)DLX2POU4F2 (BRN-3B)RBBP4SMAD4TCF4
Complex memberships
Evf2-BRG1 ribonucleoprotein complexNuRD complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Loss-of-function of both Dlx-1 and Dlx-2 produces a time-dependent block in striatal differentiation: early-born neurons migrate into a striatum-like region enriched for striosome markers, but later-born neurons accumulate within the proliferative zone, establishing Dlx1/2 as required for differentiation of late-born striatal matrix neurons and subventricular zone development. Targeted null mutations in mice with histological and marker analysis Neuron High 9247261
1997 Dlx-1 and Dlx-2 regulate proximodistal patterning of the branchial arches; mice lacking both lack maxillary molars and show ectopic skull components. Single Dlx-1 mutants affect proximal skeletal/soft tissue structures of the first and second arches, revealing overlapping and distinct roles for the two paralogs. Targeted null mutations in mice with skeletal and soft tissue analysis Developmental biology High 9187081
1997 Dlx-1 and Dlx-2 specify odontogenic potential in maxillary molar ectomesenchyme derived from cranial neural crest; in their absence, this population loses odontogenic competence and transfates toward chondrogenic identity (marked by Sox9). Heterologous tissue recombination showed the defect is ectomesenchyme-autonomous. Targeted null mutations combined with heterologous epithelial-mesenchymal recombination and molecular markers (Barx1, Sox9) Development (Cambridge, England) High 9428417
2005 Dlx1 is required cell-autonomously for the postnatal survival of specific cortical and hippocampal interneuron subtypes (calretinin+ bipolar and somatostatin+ bitufted cells), but not parvalbumin+ cells. Loss of these interneurons reduces GABA-mediated IPSCs and causes delayed-onset epilepsy. Dlx1 null mice, cell transplantation (cell-autonomy test), electrophysiology (in vitro IPSC recordings), in vivo EEG Nature neuroscience High 16007083
2007 Dlx1&2 repress oligodendrocyte precursor cell (OPC) formation by acting on a common progenitor to determine neuronal versus oligodendroglial cell fate. Progenitors from Dlx1&2 mutant ventral telencephalon transplanted into wild-type mice failed to produce neurons but differentiated into myelinating oligodendrocytes. Dlx1/2 double knockout mice, progenitor transplantation into newborn wild-type mice, immunofluorescence for oligodendrocyte markers Neuron High 17678855
2002 Dlx1 and Dlx2 downregulate Notch signaling during specification and differentiation of late SVZ progenitors (P3) in the subcortical telencephalon, complementary to Mash1 which regulates Notch/Delta signaling in earlier VZ progenitors. Analysis of Mash1, Dlx1/2, and delta-like 1 mutant mice; combinatorial marker expression; comparison of molecular phenotypes Development (Cambridge, England) Medium 12397111
2003 DLX1 protein interacts with Smad4 through its homeodomain, blocking multiple TGF-β superfamily signals (activin A, TGF-β1, BMP-4) including activin A-induced differentiation of hematopoietic cells. Co-immunoprecipitation, reporter assays, differentiation assays in hematopoietic cell lines, domain mapping Proceedings of the National Academy of Sciences of the United States of America Medium 14671321
2007 The proneural factor MASH1 directly binds to the I12b intergenic enhancer of the Dlx1/2 locus (identified by DNase I footprinting) and activates Dlx1/2 transcription in forebrain progenitors. DLX proteins also autoregulate their own expression through the I12b enhancer. DNase I footprinting, transgenic reporter assays, co-transfection experiments, in vitro mutagenesis of binding sites Development (Cambridge, England) High 17409112
2009 DLX1/2 and GSX2/1 act in a transcriptional network controlling subpallial differentiation. Loss of Gsx2 rescues elevated Ascl1, Hes5, and Olig2 expression in Dlx1/2 mutants. Loss of Gsx1 from Dlx1/2 mutants partially rescues MGE interneuron migration to cortex, demonstrating region-specific genetic interactions. Compound loss-of-function mouse mutants (Dlx1/2;Gsx1 and Dlx1/2;Gsx2), marker expression analysis The Journal of comparative neurology Medium 23042297
2012 The Rb/E2F pathway directly regulates Dlx1 and Dlx2 gene expression: repressor E2Fs bind the I12b enhancer and Dlx1/Dlx2 proximal promoter regions to suppress Dlx transcription. Rb deficiency reduces Dlx1/2 expression, causing loss of interneuron subtypes and migration defects. ChIP assays (in vitro and in vivo), Rb knockout mice, luciferase reporter assays with E2F binding site mutations The Journal of neuroscience High 22699903
2013 Dlx1&2 directly regulate Zfhx1b (Sip1/Zeb2) expression in the MGE. Zfhx1b, downstream of Dlx1&2, is required to repress Nkx2-1, enabling progenitors to adopt cortical interneuron (Cxcr7+, MafB+, cMaf+) rather than striatal interneuron identity. Conditional knockout mice, in situ hybridization, immunohistochemistry, epistasis analysis Neuron Medium 23312518
2014 Olig1 directly represses the Dlx1/2 I12b intergenic enhancer; Olig1 deletion causes ectopic upregulation of Dlx1/2 in the ventral MGE and septum, increasing adult cortical interneuron numbers by ~30%. Dlx1/2 function genetically downstream of Olig1. Olig1 knockout mice, ChIP assay (direct Olig1 binding to I12b enhancer), immunofluorescence, cell counting Neuron High 24507192
2015 DLX1 forms a ribonucleoprotein complex with the lncRNA Evf2 and the chromatin remodeler BRG1 (SMARCA4) at DNA enhancers in the developing forebrain. BRG1 directly interacts with DLX1 through a domain distinct from its RNA-binding domain. Evf2 RNA increases BRG1 association with enhancers but inhibits BRG1 ATPase and chromatin remodeling activity, converting active enhancers to repressed enhancers. Mass spectrometry (RNP complex identification), Co-IP, ChIP, in vitro BRG1 ATPase assay, chromatin remodeling assay Development (Cambridge, England) High 26138476
2013 Dlx1 expression in interneurons suppresses dendritic arborization complexity and spine density through a DNA-binding-dependent mechanism. Downstream effectors include neuropilin-2 and PAK3, whose manipulated expression phenocopies Dlx1 effects on dendritic differentiation. Ectopic expression and knockdown in hippocampal cultures, manipulation of neuropilin-2 and PAK3 expression, morphometric analysis The European journal of neuroscience Medium 24236816
2018 DLX2 directly drives expression of Gad1, Gad2, and Vgat in cortical interneurons, as demonstrated by conditional Dlx1, Dlx2, and Dlx1&2 knockouts; mutants show reduced mIPSC amplitude, fewer GABAergic synapses on excitatory neurons, and hypoplastic dendrites. Reduced GRIN2B expression was identified as a contributing mechanism. Conditional knockouts (CKOs), electrophysiology (mIPSC recordings), ChIP/reporter assays for direct gene targets, immunofluorescence Cerebral cortex High 29028947
2018 Dlx1/2 are required for specification of GHRH-neuronal identity in the hypothalamic arcuate nucleus and simultaneously suppress AgRP-neuronal fate. Dlx1/2 directly bind the Otp gene to repress its expression, and Otp is required for AgRP neuron generation, establishing a Dlx1/2-Otp regulatory axis. Dlx1/2-deficient mice, ChIP assay (direct Dlx1/2 binding to Otp gene), immunofluorescence, metabolic phenotyping Nature communications High 29795232
2016 DLX1 acts as a downstream transcriptional target of FOXM1 (both FOXM1B and FOXM1C isoforms), which binds conserved sites at +61 to +69 bp and -675 to -667 bp relative to the DLX1 promoter. DLX1 promotes ovarian cancer aggressiveness by directly interacting with SMAD4 in the nucleus upon TGF-β1 induction, upregulating PAI-1 and JUNB. Luciferase reporter assays with promoter binding site mutations, Co-IP (DLX1-SMAD4 interaction), siRNA knockdown, ectopic expression, in vivo mouse xenograft Oncogene Medium 27593933
2018 DLX1 is upregulated downstream of FLT3 signaling via the MAPK/ERK and JNK pathways in acute myeloid leukemia cells. Elevated DLX1 functionally blunts TGF-β/Smad signaling in a DLX1-dependent manner; FLT3 inhibition increases nuclear phospho-Smad2. FLT3 inhibition and activation in cell lines and patient blasts, RNA interference, western blot, reverse-phase protein array Haematologica Medium 21357706
2018 DLX1 interacts with β-catenin and enhances the interaction between β-catenin and TCF4, thereby activating β-catenin/TCF signaling to promote prostate cancer cell growth and migration. Co-immunoprecipitation (DLX1–β-catenin interaction), reporter assays, ectopic expression, cell proliferation and migration assays Experimental cell research Low 29317218
2011 Brn-3b interacts physically with DLX1 through its homeodomain and represses DLX1 transcriptional activity. This interaction suppresses amacrine cell fate and promotes RGC fate; retrovirus-mediated misexpression of DLX1/2 increases amacrine/bipolar cells and reduces rod photoreceptors. Co-immunoprecipitation (Brn-3b–DLX1 interaction), retroviral misexpression, cell counting in retinal cultures Neuroscience Medium 21875655
2017 DLX1 and DLX2 function as direct transcriptional activators of Brn3b expression in retinal ganglion cell progenitors. Dlx2 is both necessary and sufficient for Brn3b expression in vivo; Dlx1/Dlx2/Brn3b triple knockout causes near-total RGC loss greater than predicted by summing individual knockouts. Triple-knockout mice, Dlx2 knockdown in primary retinal cultures, in utero Dlx2 gain-of-function, luciferase/reporter assays Development (Cambridge, England) High 28356311
2022 DLX1 contains a motif that binds RBBP4, a NuRD complex subunit. ChIP-seq shows DLX1 and NuRD complex members co-occupy putative regulatory elements near transcription factor genes. Dlx1/2 loss dysregulates chromatin accessibility at elements near repressed genes including Olig2. Heterozygosity of both Dlx1/2 and Rbbp4 increases OLIG2+ cell production, demonstrating cooperative enhancer decommissioning. Co-IP (DLX1–RBBP4 interaction), ChIP-seq (DLX1 and 6 NuRD subunits), ATAC-seq, compound heterozygous mouse genetics Development (Cambridge, England) High 35695185
2022 Dlx1/2 regulate Meis2 expression in the lateral ganglionic eminence (LGE) at least partially through the enhancer hs599. Meis2 directly binds the Zfp503 and Six3 promoters and is required for D1 and D2 medium-sized spiny neuron differentiation, establishing a Dlx1/2 → Meis2 → Zfp503/Six3 pathway for striatal neuron fate determination. Conditional knockout mice, ChIP assay (Meis2 binding to Zfp503 and Six3 promoters), enhancer reporter analysis (hs599), immunofluorescence Development (Cambridge, England) Medium 35156680
2019 Dlx1/2 are required for differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in both the embryonic lateral ganglionic eminence and postnatal subventricular zone for olfactory bulb interneuron generation. Overexpression of Dlx1&2 in embryonic cortex causes ectopic production of OB-like interneurons, partly through activating Sp8/9 expression. Constitutive and conditional knockouts (hGFAP-Cre;Dlx1/2F/-), in utero electroporation overexpression, compound mutant analysis (Pax6;Dlx1/2) Cerebral cortex Medium 30796806
2020 Dlx1/2 are required in the enteric nervous system for normal bowel motility; Dlx1/2-/- mice have slower small bowel transit and loss of neurally mediated contraction complexes. RNA-seq of Dlx1/2-/- ENS revealed reduced Vip expression and fewer VIP-lineage neurons, identifying VIP as a downstream target in the ENS. Dlx1/2 knockout mice, bowel motility assays, RNA sequencing, immunohistochemistry, reporter mice JCI insight Medium 32017713
2011 In Dlx1-/- mice, CA1 hippocampal interneurons show a significant age-dependent reduction in excitatory postsynaptic current (EPSC) amplitude after P30, but not in younger animals. Interneurons in Dlx1-/- mutants are more excitable at early postnatal ages (P9-12), normalizing by P30, suggesting delayed maturation followed by compensatory reduction in excitatory input onto surviving interneurons. Voltage-clamp and current-clamp recordings from hippocampal slices, TUNEL/caspase-3 staining, NeuN immunostaining Journal of neurophysiology Medium 21325686
2025 DLX1 directly binds two conserved motifs within the NCS1 promoter to drive its transcriptional activation (established by ChIP and luciferase assays). NCS1 mediates DLX1-dependent oncogenicity in lung adenocarcinoma cells and acts as an upstream regulator of c-MYC, defining a DLX1–NCS1–MYC transcriptional axis. ChIP assay, luciferase reporter assay, RNA-seq, siRNA knockdown, in vivo xenograft Biochimica et biophysica acta. Molecular basis of disease Medium 40614386
2025 DLX1 protein translation escapes suppression under PERK-B (but not PERK-A) unfolded protein response conditions. DLX1 solubility shifts to a detergent-insoluble fraction in human PSP brain tissue. Silencing the Drosophila DLX1 homolog (dll) reduces tau-induced toxicity in vivo, placing DLX1 downstream of the PERK-B haplotype in a pathway promoting tau pathology. Puromycin-based proteomics (SUnSET), controlled cellular PERK haplotype comparison, detergent fractionation of human PSP brain tissue, in vivo Drosophila tau toxicity assay (dll RNAi) The Journal of neuroscience Medium 41708330
1999 DLX-1 and DLX-2 proteins are localized primarily to the nucleus in basal forebrain neurons. During M-phase, DLX-1 and DLX-2 proteins are distributed symmetrically to daughter cells. DLX-1 expression follows DLX-2 (which is expressed first) and precedes DLX-5, and these proteins are co-expressed in the same cells. Immunofluorescence with anti-DLX antibodies, confocal microscopy, analysis of M-phase cells The Journal of comparative neurology Medium 10516593
2021 Satb2 regulates development of arcuate nucleus dopaminergic neurons and Dlx1 is identified as a potential downstream gene of Satb2 in this context; conditional Satb2 CKO mice show reduced ARC DA neurons and Dlx1 expression changes. Nestin-Cre conditional knockout of Satb2, immunofluorescence, gene expression analysis Cell death & disease Low 34564702

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. The Journal of neuroscience : the official journal of the Society for Neuroscience 523 7687285
1997 Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron 443 9247261
2005 Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nature neuroscience 410 16007083
1997 Role of the Dlx homeobox genes in proximodistal patterning of the branchial arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of proximal skeletal and soft tissue structures derived from the first and second arches. Developmental biology 389 9187081
2007 Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 294 17678855
1998 Expression of the Emx-1 and Dlx-1 homeobox genes define three molecularly distinct domains in the telencephalon of mouse, chick, turtle and frog embryos: implications for the evolution of telencephalic subdivisions in amniotes. Development (Cambridge, England) 274 9570774
1999 DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. The Journal of comparative neurology 237 10516593
2002 Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon. Development (Cambridge, England) 211 12397111
1997 Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition. Development (Cambridge, England) 198 9428417
2009 Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways. Cerebral cortex (New York, N.Y. : 1991) 146 19386638
1992 Expression of the murine Dlx-1 homeobox gene during facial, ocular and limb development. Differentiation; research in biological diversity 143 1350766
2013 Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons. Neuron 133 23312518
2009 Dlx1&2 and Mash1 transcription factors control striatal patterning and differentiation through parallel and overlapping pathways. The Journal of comparative neurology 131 19030180
1997 Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic ventral lateral geniculate nuclear formation. Mechanisms of development 121 9347917
2008 Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons. Molecular and cellular neurosciences 90 19026749
2015 Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. Development (Cambridge, England) 87 26138476
2007 The proneural determinant MASH1 regulates forebrain Dlx1/2 expression through the I12b intergenic enhancer. Development (Cambridge, England) 87 17409112
2007 Distinct cis-regulatory elements from the Dlx1/Dlx2 locus mark different progenitor cell populations in the ganglionic eminences and different subtypes of adult cortical interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 87 17494687
2018 Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis. Cerebral cortex (New York, N.Y. : 1991) 73 29028947
1996 Sequence, organization, and transcription of the Dlx-1 and Dlx-2 locus. Genomics 71 8812481
2004 Dlx1 and Dlx2 function is necessary for terminal differentiation and survival of late-born retinal ganglion cells in the developing mouse retina. Development (Cambridge, England) 67 15604100
2013 Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants. The Journal of comparative neurology 65 23042297
2014 Olig1 function is required to repress dlx1/2 and interneuron production in Mammalian brain. Neuron 58 24507192
2018 Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. Nature communications 47 29795232
2016 DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-β/SMAD4 signaling. Oncogene 47 27593933
2012 The Rb/E2F pathway modulates neurogenesis through direct regulation of the Dlx1/Dlx2 bigene cluster. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 22699903
2019 Long noncoding RNA TUG1 regulates the development of oral squamous cell carcinoma through sponging miR-524-5p to mediate DLX1 expression as a competitive endogenous RNA. Journal of cellular physiology 38 30980391
2019 Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons. Cerebral cortex (New York, N.Y. : 1991) 37 30796806
2013 Making sense of Dlx1 antisense RNA. Developmental biology 37 23415800
2003 Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway from activin A in hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 37 14671321
2009 Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons. Journal of neurodevelopmental disorders 32 19816534
2022 Dlx1/2-dependent expression of Meis2 promotes neuronal fate determination in the mammalian striatum. Development (Cambridge, England) 31 35156680
2018 DLX1, a binding protein of beta-catenin, promoted the growth and migration of prostate cancer cells. Experimental cell research 29 29317218
2012 Cleft palate defect of Dlx1/2-/- mutant mice is caused by lack of vertical outgrowth in the posterior palate. Developmental dynamics : an official publication of the American Association of Anatomists 29 22972697
2017 Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina. Development (Cambridge, England) 28 28356311
2012 Helios transcription factor expression depends on Gsx2 and Dlx1&2 function in developing striatal matrix neurons. Stem cells and development 26 22142223
2003 Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation. The Journal of comparative neurology 26 12722102
2018 Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1. Nature communications 23 30050033
2011 Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons. Journal of neurophysiology 19 21325686
2011 Up-regulation of homeodomain genes, DLX1 and DLX2, by FLT3 signaling. Haematologica 18 21357706
2004 Identification and characterization of a novel transcript down-regulated in Dlx1/Dlx2 and up-regulated in Pax6 mutant telencephalon. Developmental dynamics : an official publication of the American Association of Anatomists 18 15376329
2003 Decreased thalamic expression of the homeobox gene DLX1 in psychosis. Archives of general psychiatry 18 12963668
2022 DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression. Development (Cambridge, England) 17 35695185
2019 MicroRNA-539 functions as a tumour suppressor in prostate cancer via the TGF-β/Smad4 signalling pathway by down-regulating DLX1. Journal of cellular and molecular medicine 17 31298493
2013 Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression. The European journal of neuroscience 17 24236816
2020 Dlx1/2 mice have abnormal enteric nervous system function. JCI insight 14 32017713
2014 Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells. PloS one 14 24489801
2023 Detection of DNA Methylation in Gene Loci ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671 for Diagnosis of Cervical Cancer. Cancer management and research 12 37457377
2020 miR-489-3p Inhibits Prostate Cancer Progression by Targeting DLX1. Cancer management and research 10 32368149
2011 Brn-3b inhibits generation of amacrine cells by binding to and negatively regulating DLX1/2 in developing retina. Neuroscience 10 21875655
2023 The performance and limitations of PCA3, TMPRSS2:ERG, HOXC6 and DLX1 urinary markers combined in the improvement of prostate cancer diagnostics. Clinical biochemistry 8 37121562
2021 miR-184 delays cell proliferation, migration and invasion in prostate cancer by directly suppressing DLX1. Experimental and therapeutic medicine 8 34504608
2021 Satb2 regulates the development of dopaminergic neurons in the arcuate nucleus by Dlx1. Cell death & disease 8 34564702
2021 MiR-129-5p/DLX1 signalling axis mediates functions of prostate cancer during malignant progression. Andrologia 7 34472106
2022 The distribution of Dlx1-2 and glutamic acid decarboxylase in the embryonic and adult hypothalamus reveals three differentiated LHA subdivisions in rodents. Journal of chemical neuroanatomy 3 35283254
2009 Expression of Msx1 and Dlx1 during Dumbo rat head development: Correlation with morphological features. Genetics and molecular biology 3 21637698
2025 miR-1224 Controls Mammal Cerebral Cortex Development by Targeting the 3'-UTR of the Dlx1 mRNA. Journal of cellular physiology 2 39745107
2013 [Role of Dlx1 natural antisense transcript in mice brain development]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 2 24382236
2025 The DLX1-NCS1-MYC axis drives oncogenesis and progression in lung adenocarcinoma. Biochimica et biophysica acta. Molecular basis of disease 1 40614386
2024 Six1 Regulates Mouse Incisor Development by Promoting Dlx1/2/5 Expression. Journal of dental research 1 39101661
2026 Progressive Supranuclear Palsy PERK Haplotype B Selectively Translates DLX1 Promoting Tau Toxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 41708330
2025 Progressive Supranuclear Palsy PERK haplotype B selectively translates DLX1 promoting tau toxicity. bioRxiv : the preprint server for biology 0 40631137
2025 Identification of prostate cancer by urinary DLX1/HOXC6 expression in Chinese population with prostate-specific antigen levels of 4-10 ng/mL. Scientific reports 0 41461862
2011 [Immunohistochemical study of Dlx1 and Msx1 expression during cephalic development of Dumbo and Wistar rats. Correlation with morphological data]. Morphologie : bulletin de l'Association des anatomistes 0 22099937

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