Affinage

DLX1

Homeobox protein DLX-1 · UniProt P56177

Length
255 aa
Mass
27.3 kDa
Annotated
2026-04-28
64 papers in source corpus 29 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLX1 is a homeodomain transcription factor that functions as both a transcriptional activator and repressor to orchestrate neuronal differentiation, subtype specification, and fate restriction across multiple regions of the developing and postnatal nervous system. In the forebrain, DLX1 (often acting redundantly with DLX2) is required for differentiation of striatal neurons and olfactory bulb interneurons from subventricular zone progenitors, directly activates GABAergic genes (Gad1, Gad2, Vgat) and the retinal ganglion cell determinant Brn3b, and represses alternative fates — including oligodendrocyte and specific hypothalamic neuron identities — by recruiting the NuRD chromatin-remodeling complex via direct interaction with RBBP4 and by binding and repressing Otp and Olig2 loci (PMID:9247261, PMID:29028947, PMID:35695185, PMID:29795232, PMID:28356311). DLX1 autoregulates its own expression through the I12b/URE2 intergenic enhancers and participates in a lncRNA Evf2–BRG1–DLX1 ribonucleoprotein complex in which Evf2 inhibits BRG1 ATPase activity to switch enhancers from active to repressed states (PMID:17409112, PMID:26138476). Postnatally, DLX1 is required cell-autonomously for survival of calretinin+ and somatostatin+ cortical interneurons, and its loss causes reduced GABAergic inhibition and epilepsy; DLX1 also physically interacts with SMAD4 to antagonize TGF-β superfamily signaling (PMID:16007083, PMID:14671321).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Establishing that DLX1/2 are required for telencephalic and craniofacial development resolved the question of whether these homeodomain factors had essential roles beyond expression markers — double knockouts revealed blocks in striatal subventricular zone differentiation and conversion of odontogenic to chondrogenic fate in branchial arches.

    Evidence Dlx1/Dlx2 double-knockout mice with histological, marker, and tissue-recombination analysis

    PMID:9187081 PMID:9247261 PMID:9428417

    Open questions at the time
    • Individual contribution of DLX1 versus DLX2 not resolved at this stage
    • Downstream transcriptional targets not identified
    • Mechanism of fate conversion (direct vs. indirect) unknown
  2. 2002 Medium

    Placing DLX1/2 downstream of Mash1 in the temporal hierarchy of subventricular zone neurogenesis established that DLX1/2 promote differentiation by downregulating Notch signaling at a late progenitor stage, answering how sequential transcription factors coordinate the transition from progenitor to neuron.

    Evidence Genetic epistasis analysis combining Dlx1/2, Mash1, and Dll1 mutants with progenitor-stage markers

    PMID:12397111

    Open questions at the time
    • Biochemical mechanism by which DLX1/2 downregulate Notch not reconstituted
    • Whether DLX1/2 directly repress Notch pathway genes or act indirectly remains unclear
  3. 2003 Medium

    Demonstrating that DLX1 physically interacts with SMAD4 and blocks TGF-β/BMP signaling revealed a non-transcriptional mechanism — protein–protein sequestration — by which DLX1 controls cell differentiation, extending its functional repertoire beyond DNA-binding-dependent gene regulation.

    Evidence Co-immunoprecipitation of DLX1 homeodomain with SMAD4, reporter assays, functional block of activin-induced hematopoietic differentiation

    PMID:14671321

    Open questions at the time
    • Interaction validated in overexpression system only; endogenous co-IP in neural tissue lacking
    • Structural basis of homeodomain–SMAD4 interaction not determined
    • Physiological significance in forebrain development not tested
  4. 2005 High

    Demonstrating that DLX1 alone (not just DLX1/2 together) is cell-autonomously required for postnatal survival of specific interneuron subtypes and that its loss causes epilepsy via reduced GABAergic inhibition answered whether DLX1 has non-redundant postnatal functions distinct from its embryonic role with DLX2.

    Evidence Dlx1 single knockout with cell transplantation, electrophysiology (IPSCs), and EEG recording

    PMID:16007083

    Open questions at the time
    • Transcriptional targets mediating interneuron survival not identified
    • Whether DLX1 directly controls anti-apoptotic or trophic factor genes unknown
    • Mechanism of subtype specificity (calretinin+/somatostatin+ but not parvalbumin+) not explained
  5. 2007 High

    Two discoveries — DLX1/2 autoregulation through the I12b enhancer and their repression of oligodendrocyte fate — established that DLX1/2 both sustain their own expression via a positive feedback loop and actively suppress glial identity, answering how a binary neuron-vs-glia fate decision is enforced in ventral telencephalic progenitors.

    Evidence DNase I footprinting, mutagenesis of I12b binding sites, transgenic reporters, and progenitor transplantation showing cell-autonomous fate switch to myelinating oligodendrocytes in Dlx1/2 mutants

    PMID:17409112 PMID:17678855

    Open questions at the time
    • Direct DLX1 binding sites on oligodendrocyte-lineage genes not mapped at this stage
    • Whether repression of OPC fate requires co-repressor recruitment unknown
  6. 2011 Medium

    Finding that Brn3b physically interacts with the DLX1 homeodomain in retina and that FLT3 signaling upregulates DLX1 to suppress SMAD signaling in AML expanded DLX1's known protein interaction network and linked it to both retinal and hematopoietic contexts beyond the forebrain.

    Evidence Co-immunoprecipitation and retroviral misexpression in retina; FLT3 inhibitor/RNAi in AML cells with phospho-Smad2 readout

    PMID:21357706 PMID:21875655

    Open questions at the time
    • Brn3b–DLX1 interaction not validated by reciprocal pull-down or endogenous co-IP
    • Relevance of FLT3–DLX1–SMAD axis in normal hematopoiesis not established
  7. 2012 High

    Identifying E2F-dependent regulation of DLX1/2 transcription via Rb connected cell cycle exit machinery to interneuron differentiation programs, answering how proliferative signals are coupled to DLX1/2 induction.

    Evidence Rb knockout with ChIP showing E2F binding to Dlx1/2 promoters and I12b enhancer, plus reporter assays

    PMID:22699900

    Open questions at the time
    • Whether activating E2Fs directly drive or repressor E2Fs suppress DLX1/2 in different contexts not fully delineated
    • Post-translational regulation of DLX1 by cell cycle kinases not investigated
  8. 2013 High

    Multiple studies converged to define DLX1/2's position in transcriptional hierarchies: Dlx1/2→Zfhx1b for cortical vs. striatal interneuron fate, Gsx2 downstream of Dlx1/2 in LGE, and DLX1 as a repressor of dendritic growth via neuropilin-2 and PAK3 — collectively building a pathway map from upstream inputs to downstream effectors.

    Evidence Compound knockout epistasis (Dlx1/2;Zfhx1b, Dlx1/2;Gsx2, Dlx1/2;Gsx1), hippocampal culture gain/loss-of-function with DNA-binding mutant

    PMID:23042297 PMID:23312518 PMID:24236816

    Open questions at the time
    • Direct DLX1 binding to Zfhx1b regulatory elements not shown
    • Whether DLX1 and DLX2 have distinct versus overlapping targets in these hierarchies unresolved
    • PAK3 and Nrp2 repression shown only in culture
  9. 2015 High

    Discovery that the lncRNA Evf2 recruits DLX1 and BRG1 into a ribonucleoprotein complex and directly inhibits BRG1 ATPase activity resolved how an activating transcription factor (DLX1) at an enhancer can paradoxically lead to enhancer repression — through RNA-mediated inhibition of the chromatin remodeler it co-recruits.

    Evidence Mass spectrometry, co-IP, ChIP, in vitro ATPase assay reconstitution, chromatin remodeling assay

    PMID:26138476

    Open questions at the time
    • Genome-wide extent of Evf2-dependent DLX1–BRG1 repressive complexes not mapped
    • Whether other lncRNAs similarly redirect DLX1 function unknown
    • Structural basis of Evf2–BRG1 inhibition not determined
  10. 2018 High

    Three parallel advances established DLX1/2 as direct transcriptional activators of GABAergic genes (Gad1/2, Vgat) and Brn3b for retinal ganglion cell specification, and as direct repressors of Otp for hypothalamic neuron fate — defining DLX1/2 as dual-function transcription factors whose activator vs. repressor role is target-dependent.

    Evidence ChIP for DLX2 at Gad1/Gad2/Vgat; conditional KOs with electrophysiology and morphometry; DLX1/2 ChIP at Otp; triple KO epistasis in retina

    PMID:28356311 PMID:29028947 PMID:29795232

    Open questions at the time
    • What determines whether DLX1/2 activate or repress at a given locus not mechanistically explained
    • Relative contributions of DLX1 vs. DLX2 to each target remain partially conflated
  11. 2022 High

    Identification of a direct DLX1–RBBP4 (NuRD) binding motif and genome-wide co-occupancy with NuRD at enhancers near fate-determining genes answered how DLX1 executes transcriptional repression mechanistically — through recruitment of a chromatin-remodeling/deacetylase complex — and genetic interaction with Rbbp4 confirmed functional cooperation in suppressing Olig2+ cell production.

    Evidence DLX1 motif–RBBP4 binding, ChIP-seq for DLX1 and 6 NuRD subunits, ATAC-seq, compound heterozygous genetics

    PMID:35695185

    Open questions at the time
    • Whether DLX1–NuRD interaction is constitutive or regulated is unknown
    • Crystal structure of DLX1–RBBP4 interface not determined
    • Whether DLX1 also uses NuRD for repression outside telencephalon not tested
  12. 2022 High

    Placing DLX1/2 upstream of Meis2 and subsequently Zfp503/Six3 for D1/D2 medium spiny neuron specification filled a gap in how DLX1/2 control striatal neuron subtype diversification beyond the initial neuronal-vs-glial decision.

    Evidence Meis2 conditional KO, Dlx1/2 mutant enhancer analysis, ChIP for Meis2 binding to Zfp503/Six3 promoters

    PMID:35156680

    Open questions at the time
    • Whether DLX1 binds the Meis2 hs599 enhancer directly or indirectly regulates it not fully resolved
    • How DLX1/2 differentially control D1 vs. D2 MSN ratios unknown
  13. 2025 Medium

    Two recent studies expanded DLX1 biology beyond development: DLX1 protein undergoes a solubility shift in PSP brain downstream of PERK haplotype-B-selective translation, and DLX1 directly activates NCS1 transcription in lung cancer cells, defining a DLX1→NCS1→MYC oncogenic axis.

    Evidence Puromycin proteomics with PERK haplotype models, biochemical fractionation of PSP brain, Drosophila tau model; ChIP and luciferase at NCS1 promoter with in vivo xenograft rescue

    PMID:40614386 PMID:41708330

    Open questions at the time
    • Mechanism by which DLX1 aggregation contributes to tau pathology not elucidated
    • Whether DLX1→NCS1 axis operates in normal lung or other tissues unknown
    • Therapeutic targetability of DLX1 in either context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include how DLX1 switches between activator and repressor modes at different genomic targets, the structural basis of its interactions with NuRD, BRG1, and SMAD4, and whether its non-redundant roles relative to DLX2 depend on distinct protein interactions or expression timing.
  • No structural model for DLX1 homeodomain with any partner
  • Activator-vs-repressor switch mechanism unknown
  • DLX1-specific versus DLX2-specific target genes not systematically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 5
Pathway
R-HSA-1266738 Developmental Biology 9 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 2
Partners
ASCL1DLX2POU4F2RBBP4SMAD4SMARCA4
Complex memberships
Evf2–BRG1–DLX1 ribonucleoprotein complexNuRD complex (via RBBP4)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Dlx-1 and Dlx-2 double knockout mice show a time-dependent block in striatal differentiation: early-born neurons migrate normally, but later-born neurons accumulate in the proliferative zone, establishing that Dlx-1 and Dlx-2 are required for development of the striatal subventricular zone and differentiation of late-born striatal matrix neurons. Targeted gene knockout (loss-of-function) with histological and marker analysis of striatal differentiation Neuron High 9247261
1997 Dlx-1 and Dlx-2 regulate proximodistal patterning of the branchial arches; mice lacking both genes lack maxillary molars and show conversion of odontogenic ectomesenchyme to a chondrogenic fate, demonstrating that Dlx-1 and Dlx-2 specify odontogenic identity in cranial neural crest-derived ectomesenchyme. Targeted knockout, heterologous tissue recombination, molecular marker analysis (Barx1, Sox9) Developmental biology / Development High 9187081 9428417
2005 Dlx1 is required cell-autonomously for the postnatal survival of specific cortical and hippocampal interneuron subtypes (calretinin+ and somatostatin+ cells), and its loss leads to reduced GABA-mediated IPSCs and delayed-onset epilepsy; parvalbumin+ interneurons are unaffected. Dlx1 germline knockout, cell transplantation (cell-autonomous test), electrophysiology (IPSC recordings), EEG Nature neuroscience High 16007083
2007 Dlx1 and Dlx2 transcription factors repress oligodendrocyte precursor cell (OPC) formation in ventral telencephalic progenitors by acting on a common progenitor to determine neuronal versus oligodendroglial cell fate; in Dlx1&2 mutant progenitors transplanted into wild-type mice, cells differentiate into myelinating oligodendrocytes instead of neurons. Conditional knockout, progenitor transplantation into wild-type neonates, lineage tracing Neuron High 17678855
2002 Dlx1 and Dlx2 homeobox transcription factors downregulate Notch signaling during specification and differentiation of late subventricular zone progenitors (P3 stage), complementing Mash1's role in early neurogenesis through Notch; this positions Dlx1/2 downstream in the temporal control of subcortical telencephalic neurogenesis. Genetic epistasis with Mash1 and Delta-like 1 mutants, combinatorial marker analysis of progenitor stages Development Medium 12397111
2003 DLX1 interacts directly with Smad4 through its homeodomain and blocks TGF-β superfamily signaling (activin A, TGF-β1, BMP-4), including inhibition of activin A-induced differentiation of hematopoietic cells. Co-immunoprecipitation, reporter assays, functional differentiation block assays in hematopoietic cell lines PNAS Medium 14671321
2007 MASH1 directly binds the I12b intergenic enhancer of the Dlx1/2 locus and regulates Dlx1/2 forebrain expression; additionally, DLX proteins directly bind I12b to maintain their own expression in an autoregulatory loop, demonstrated by DNase I footprinting, transgenic reporter assays, and co-transfection experiments. DNase I footprinting, site-directed mutagenesis of enhancer binding sites, transgenic reporter mice, co-transfection assays Development High 17409112
2009 Dlx1 and Dlx2 are required for the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the lateral ganglionic eminence into olfactory bulb interneurons; overexpression of Dlx1&2 in cortex ectopically produces OB-like interneurons, and the effect requires downstream activation of Sp8/9. Constitutive and conditional knockout, gain-of-function (in utero electroporation), compound mutant analysis Cerebral cortex High 30796806
2013 Dlx1&2 act directly upstream of Zfhx1b (Sip1/Zeb2) in the medial ganglionic eminence; loss of Zfhx1b in MGE prevents repression of Nkx2-1 and causes cells destined to become cortical interneurons to adopt a striatal interneuron fate, revealing a DLX1/2→Zfhx1b pathway for the cortical vs. striatal interneuron fate switch. Conditional knockout, genetic epistasis, transcription factor expression analysis Neuron High 23312518
2013 Compound loss of Gsx2 in Dlx1/2 mutants rescues overexpression of Ascl1, Hes5, and Olig2, placing Gsx2 downstream of Dlx1/2 in the LGE/CGE/septum transcriptional hierarchy; loss of Gsx1 in Dlx1/2 mutants partially rescues MGE properties including cortical interneuron migration. Compound loss-of-function mouse genetics, transcription factor marker analysis Journal of comparative neurology Medium 23042297
2014 Olig1 directly represses the Dlx1/2 I12b intergenic enhancer; Olig1 deletion causes ectopic upregulation of Dlx1/2 and an ~30% increase in adult cortical interneuron numbers, establishing Olig1 as a direct upstream repressor of Dlx1/2 expression. Olig1 knockout, ChIP-seq/reporter assay for direct Olig1 binding to I12b, interneuron counting Neuron High 24507192
2015 The lncRNA Evf2 recruits DLX1 and the chromatin remodeler BRG1 (SMARCA4/BAF) into a ribonucleoprotein complex at Dlx1/2 enhancers in the developing forebrain; Evf2 RNA directly inhibits BRG1 ATPase and chromatin remodeling activity, converting an active enhancer to a repressed state despite stabilizing DLX1 at the enhancer. BRG1 interacts with DLX1 and Evf2 through distinct binding sites. Mass spectrometry, Co-IP, ChIP, in vitro ATPase assay, chromatin remodeling assay, nuclear colocalization imaging Development High 26138476
2016 FOXM1 transcriptionally upregulates DLX1 through two conserved binding sites in the DLX1 promoter; DLX1 then promotes ovarian cancer cell invasion and intraperitoneal dissemination by directly interacting with SMAD4 in the nucleus upon TGF-β1 induction, upregulating PAI-1 and JUNB. Promoter luciferase assays, ChIP, Co-IP (DLX1–SMAD4 interaction), siRNA knockdown, in vivo xenograft Oncogene Medium 27593933
2018 DLX2 directly drives expression of Gad1, Gad2, and Vgat in cortical interneurons; conditional Dlx1/2 knockouts have reduced mIPSC amplitude, fewer GABAergic synapses on excitatory neurons, hypoplastic dendrites, and reduced GRIN2B expression, demonstrating that Dlx1&2 coordinate GABA synthesis, synaptogenesis, and dendritogenesis postnatally. Conditional knockout (Dlx1, Dlx2, Dlx1&2 CKOs), ChIP for direct DLX2 binding to Gad1/Gad2/Vgat, electrophysiology (mIPSC), morphometric analysis Cerebral cortex High 29028947
2018 Dlx1/2 are required for specification of GHRH-neuron identity in the hypothalamic arcuate nucleus and simultaneously suppress AgRP-neuron fate; mechanistically, Dlx1/2 repress Otp expression by directly binding the Otp gene, and Otp is required for AgRP-neuron generation. Dlx1/2 conditional knockout, ChIP (DLX1/2 binding to Otp gene), phenotypic analysis of GHRH and AgRP neuron numbers Nature communications High 29795232
2022 DLX1 contains a motif that directly binds RBBP4, a NuRD complex subunit; ChIP-seq shows DLX1 and NuRD co-localize at regulatory elements near transcription factor genes; Dlx1/2 loss disrupts chromatin accessibility at these elements (including near Olig2); Dlx1/2 and Rbbp4 heterozygosity together increase OLIG2+ cell production, establishing DLX1–NuRD cooperation in enhancer decommissioning and cell-fate repression. Protein interaction (DLX1 motif–RBBP4 binding), ChIP-seq (DLX1 and 6 NuRD subunits), ATAC-seq, compound heterozygous genetics Development High 35695185
2022 Dlx1/2 regulate expression of Meis2 in the lateral ganglionic eminence at least partially through direct action on the enhancer hs599; Meis2 in turn directly binds the Zfp503 and Six3 promoters to promote D1 and D2 MSN fate determination, placing Dlx1/2 upstream of Meis2 in the striatal neuronal specification pathway. Meis2 conditional knockout, Dlx1/2 mutant analysis, ChIP (Meis2 binding to Zfp503 and Six3 promoters), enhancer reporter assay Development High 35156680
2012 The Rb/E2F pathway directly regulates Dlx1 and Dlx2 transcription: Rb deficiency reduces Dlx1/Dlx2 expression via repressor E2F sites at the Dlx1/Dlx2 proximal promoters and the I12b enhancer, demonstrated by ChIP in vivo and reporter assays in vitro, linking cell cycle machinery to interneuron differentiation and migration. Rb knockout, ChIP (E2F binding to Dlx1/2 promoters and I12b), reporter assays, interneuron subtype and migration analysis Journal of Neuroscience High 22699900
2008 Both I12b and URE2 cis-regulatory elements of the Dlx1/2 locus are direct targets of DLX2 and require Dlx1 and Dlx2 expression for proper activity in vivo, providing in vivo evidence for autoregulation of Dlx1/2 expression through these enhancers. Cre-transgenic mice with I12b and URE2 enhancers, fate mapping, Dlx1/2 mutant enhancer activity assays Molecular and cellular neurosciences Medium 19026749
2013 DLX1 transcription factor regulates dendritic growth and postsynaptic differentiation in interneurons by repressing neuropilin-2 and PAK3 expression in a DNA-binding-dependent manner; knockdown of Dlx1 in interneurons enhances dendritic growth, while overexpression in pyramidal neurons reduces dendritic complexity. Overexpression/knockdown in hippocampal culture, DNA-binding domain mutant, manipulation of downstream effectors (neuropilin-2, PAK3) European Journal of Neuroscience Medium 24236816
2011 Brn-3b physically interacts with DLX1 through its homeodomain, repressing DLX1 transcriptional activity; this interaction biases retinal progenitors toward RGC fate and away from amacrine cell fate, as shown by retroviral misexpression and combined ectopic expression experiments. Co-immunoprecipitation (Brn-3b–DLX1 homeodomain interaction), retroviral misexpression in retina, combinatorial overexpression Neuroscience Medium 21875655
2017 DLX1 and DLX2 directly activate Brn3b expression in the developing retina, functioning as transcriptional activators of retinal ganglion cell differentiation; Dlx1/Dlx2/Brn3b triple knockout shows near-total RGC loss with amacrine cell increase, more severe than single or double KOs, placing DLX1/2 both downstream of ATOH7 and in a parallel cooperative pathway with Brn3b. Triple knockout mouse, Dlx2 knockdown in primary retinal cultures, Dlx2 gain-of-function (in utero electroporation), reporter assays Development High 28356311
2011 FLT3 activation upregulates DLX1/2 expression through MAPK/ERK and JNK signaling pathways in AML cells; elevated DLX1 in turn blunts TGF-β/Smad signaling (nuclear phospho-Smad2 increases upon FLT3 inhibition in a DLX1-dependent manner), linking FLT3 signaling to DLX1-mediated Smad pathway suppression. FLT3 inhibitor treatment, FLT3 activation, RNA interference (DLX1 knockdown), reverse-phase protein array, western blot for phospho-Smad2 Haematologica Medium 21357706
2018 DLX1 interacts with beta-catenin and enhances the interaction between beta-catenin and TCF4, thereby activating beta-catenin/TCF signaling to promote prostate cancer cell growth and migration. Co-immunoprecipitation (DLX1–beta-catenin), reporter assays, overexpression in prostate cancer cells Experimental cell research Low 29317218
2020 Dlx1/2 are required for normal enteric nervous system function: Dlx1/2-/- mice show slower small bowel transit and loss of neurally mediated contraction complexes, accompanied by dysregulation of Vip expression and fewer VIP-lineage neurons, without gross changes in neuronal or glial density. Dlx1/2 knockout, GI motility assays, RNA sequencing of ENS, immunohistochemistry, reporter mice for VIP lineage JCI insight Medium 32017713
2013 The Dlx1 antisense lncRNA (Dlx1as) inversely regulates Dlx1 transcript levels; mice devoid of Dlx1as show a mild phenotype resembling Dlx1 gain-of-function, indicating that Dlx1as modulates Dlx1 mRNA stability/levels. Targeted ablation of Dlx1as lncRNA in vivo, skeletal and neurological phenotyping, quantitative expression analysis Developmental biology Medium 23415800
2025 PERK haplotype B (associated with PSP risk) permits selective translation of DLX1 mRNA under UPR conditions where PERK-A suppresses it; DLX1 undergoes a solubility shift to detergent-insoluble fractions in PSP brain, and silencing the Drosophila DLX1 homolog reduces tau-induced toxicity in vivo, placing DLX1 downstream of PERK-B in a tau pathology pathway. Puromycin-based proteomics (SUnSET), controlled PERK haplotype cellular model, biochemical fractionation of human PSP brain tissue, Drosophila tau toxicity model with DLX1 homolog knockdown Journal of Neuroscience Medium 41708330
2025 DLX1 directly binds two conserved motifs in the NCS1 promoter to drive NCS1 transcriptional activation, establishing NCS1 as a direct transcriptional target; NCS1 then activates c-MYC, defining a DLX1→NCS1→MYC oncogenic axis in lung adenocarcinoma. ChIP assay, luciferase reporter assay, DLX1 silencing with rescue by NCS1 overexpression, in vivo xenograft Biochimica et biophysica acta. Molecular basis of disease Medium 40614386

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 409 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 388 9187081
2007 Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 293 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 238 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) 210 12397111
1997 Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition. Development (Cambridge, England) 195 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 132 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 89 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) 71 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 57 24507192
2016 DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-β/SMAD4 signaling. Oncogene 47 27593933
2018 Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. Nature communications 46 29795232
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
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
2019 Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons. Cerebral cortex (New York, N.Y. : 1991) 36 30796806
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
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 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 28 22972697
2018 DLX1, a binding protein of beta-catenin, promoted the growth and migration of prostate cancer cells. Experimental cell research 27 29317218
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 22 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 13 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 11 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
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
2023 The performance and limitations of PCA3, TMPRSS2:ERG, HOXC6 and DLX1 urinary markers combined in the improvement of prostate cancer diagnostics. Clinical biochemistry 7 37121562
2021 MiR-129-5p/DLX1 signalling axis mediates functions of prostate cancer during malignant progression. Andrologia 7 34472106
2009 Expression of Msx1 and Dlx1 during Dumbo rat head development: Correlation with morphological features. Genetics and molecular biology 3 21637698
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 2 35283254
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 miR-1224 Controls Mammal Cerebral Cortex Development by Targeting the 3'-UTR of the Dlx1 mRNA. Journal of cellular physiology 1 39745107
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 The DLX1-NCS1-MYC axis drives oncogenesis and progression in lung adenocarcinoma. Biochimica et biophysica acta. Molecular basis of disease 0 40614386
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