Affinage

LHX6

LIM/homeobox protein Lhx6 · UniProt Q9UPM6

Length
363 aa
Mass
40.0 kDa
Annotated
2026-04-28
59 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LHX6 is a LIM-homeodomain transcription factor that serves as a master regulator of GABAergic cortical interneuron specification, migration, and subtype identity, while also functioning in craniofacial morphogenesis and hypothalamic sleep circuitry. Activated downstream of NKX2.1 via direct promoter binding (PMID:18339674), LHX6 directly binds enhancers of target genes including Arx, CXCR7, and Shh to specify parvalbumin- and somatostatin-expressing interneuron subtypes, promote tangential migration through ErbB4/CXCR4/CXCR7 expression, and non-cell-autonomously sustain MGE progenitor programs via neuronal Shh signaling (PMID:17376969, PMID:24742460, PMID:21658586); it interacts with co-factors Ldb1, MTG8, and PITX2 to execute context-dependent transcriptional activation or repression (PMID:10393337, PMID:36064547, PMID:23229549). LHX6 is essential during development but dispensable for maintenance of mature cortical interneurons (PMID:35318414); beyond the brain, it cooperates with LHX8 to regulate tooth and palate morphogenesis through repression of p57Kip2 and modulation of Wnt signaling (PMID:19591819, PMID:33596195, PMID:26071365), and in the ventral zona incerta it marks GABAergic neurons that directly inhibit hypocretin cells to promote sleep (PMID:28847002).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 Medium

    Establishing that Lhx6 expression in craniofacial mesenchyme is patterned by epithelial signals, specifically FGF8, placed LHX6 within the signaling hierarchy governing mandibular and maxillary development.

    Evidence FGF8 bead implantation in explant cultures with whole-mount in situ hybridization

    PMID:9570771

    Open questions at the time
    • Mechanism of FGF8-mediated Lhx6 transcriptional regulation not defined
    • No loss-of-function test for craniofacial role at this stage
  2. 1999 Medium

    Identification of Ldb1 as a physical interaction partner of Lhx6 through its LIM domains provided the first evidence that LHX6 operates within a LIM-domain cofactor complex, a hallmark of LIM-homeodomain transcriptional regulation.

    Evidence Protein pulldown/interaction assay using tandem LIM-domains of Lhx6.1

    PMID:10393337

    Open questions at the time
    • Functional consequence of Ldb1-Lhx6 interaction on transcription not tested
    • No reciprocal co-IP or in vivo validation
  3. 2004 High

    Demonstrating that Lhx6 knockdown blocks tangential migration of MGE-derived interneurons without affecting GABA synthesis established LHX6 as a migration regulator separable from neurotransmitter identity.

    Evidence siRNA knockdown in mouse embryonic brain slices and dissociated MGE cultures with GABA/GAD assay

    PMID:15201337

    Open questions at the time
    • Downstream migration effectors not yet identified
    • In vivo genetic confirmation pending at this point
  4. 2007 High

    Genetic loss-of-function confirmed LHX6 as required for specification of parvalbumin+ and somatostatin+ cortical interneuron subtypes and for normal migration, establishing it as a subtype-selector transcription factor rather than a general interneuron gene.

    Evidence Lhx6 knockout mouse with immunofluorescence for PV, SST, and other interneuron markers

    PMID:17376969

    Open questions at the time
    • Direct transcriptional targets mediating subtype specification unknown
    • Whether LHX6 acts in specification versus maintenance not resolved
  5. 2008 High

    Placing LHX6 directly downstream of NKX2.1 via ChIP and rescue experiments defined the core transcriptional cascade (NKX2.1→LHX6→PV/SST fate) governing MGE-derived interneuron identity, and identified downstream molecular effectors including ErbB4, CXCR4, CXCR7, and Arx.

    Evidence ChIP for NKX2.1 at Lhx6 promoter, electroporation rescue in Nkx2.1-/- slices, and molecular profiling of Lhx6 mutants

    PMID:18339674 PMID:18613121

    Open questions at the time
    • Whether LHX6 directly binds regulatory regions of migration receptor genes not yet shown
    • Cofactors mediating context-specific activation vs. repression unknown
  6. 2009 High

    Double knockout of Lhx6 and Lhx7 revealed redundant requirements in molar tooth specification and palate closure, extending LHX6 function beyond neurodevelopment to craniofacial morphogenesis.

    Evidence Lhx6;Lhx7 double-knockout mouse with histological analysis

    PMID:19591819

    Open questions at the time
    • Downstream targets in dental mesenchyme not identified
    • Relative individual contributions of Lhx6 vs Lhx7 in craniofacial tissues unclear
  7. 2011 High

    Showing that Lhx6/Lhx8 coexpression induces neuronal Shh via enhancer regulation revealed a non-cell-autonomous feedback mechanism where early-born MGE neurons signal back to progenitors to sustain late-born interneuron production.

    Evidence Conditional Shh deletion in MGE mantle zone, reporter assays, gene expression analysis in mouse

    PMID:21658586

    Open questions at the time
    • Whether Lhx6 directly binds the Shh enhancer or acts indirectly not fully resolved
    • Quantitative contribution of this feedback to final interneuron numbers undefined
  8. 2012 High

    Identification of LHX6 as a transcriptional repressor that directly interacts with PITX2 and inhibits PITX2/LEF-1/β-catenin-driven transcription revealed how LHX6 modulates Wnt signaling during odontogenesis, while a hypomorphic allele showed dose-dependent effects on SST+ interneuron maturation and seizure susceptibility.

    Evidence ChIP, BiFC, promoter reporter assays, Lhx6 null mouse for dental studies; hypomorphic Lhx6 allele with electrophysiology and EEG for interneuron studies

    PMID:22710612 PMID:23229549

    Open questions at the time
    • Structural basis of LHX6-PITX2 interaction not determined
    • Whether repressor function extends to neuronal targets unknown
  9. 2014 High

    Direct in vivo ChIP demonstrated LHX6 occupancy at Arx and CXCR7 enhancers, and rescue experiments showed these targets mediate separable functions—cell fate versus laminar positioning—resolving how a single transcription factor controls distinct aspects of interneuron development.

    Evidence In vivo ChIP at enhancers, MGE transplantation/complementation assay in Lhx6-/- cells

    PMID:24742460

    Open questions at the time
    • Full genomic binding landscape of LHX6 not mapped
    • How combinatorial cofactor interactions specify enhancer selection unresolved
  10. 2015 High

    LHX6/LHX8 were shown to repress the cell cycle inhibitor p57Kip2 to promote palatal cell proliferation, and cross-species rescue in C. elegans demonstrated deep conservation of LHX6's terminal selector function for cholinergic/peptidergic neuron differentiation.

    Evidence ChIP and reporter assays for p57Kip2 regulation in palate; lim-4 mutant rescue with human LHX6 in C. elegans plus human neuronal cell line assays

    PMID:26071365 PMID:26305787

    Open questions at the time
    • Full set of direct palatal targets beyond p57Kip2 not catalogued
    • Whether terminal selector function applies to mammalian interneuron maintenance unclear
  11. 2017 High

    Identifying Lhx6+ zona incerta neurons as sleep-promoting GABAergic cells that directly inhibit hypocretin neurons expanded LHX6's functional repertoire beyond development into adult circuit-level physiology.

    Evidence Conditional Lhx6 deletion in diencephalon, optogenetic activation/inhibition, chemogenetics, EEG/EMG sleep recording, retrograde tracing

    PMID:28847002

    Open questions at the time
    • Whether Lhx6 transcriptional targets in zona incerta neurons differ from cortical interneuron targets unknown
    • Molecular mechanism linking Lhx6 expression to sleep-regulating ion channel/receptor repertoire undefined
  12. 2020 High

    Ras/MEK signaling was identified as an upstream regulator of Lhx6 expression via neurofibromin, connecting a major growth factor pathway to cortical interneuron specification.

    Evidence Conditional Nf1 deletion from MGE with MEK inhibitor SL327 rescue of Lhx6 expression

    PMID:32123116

    Open questions at the time
    • Whether MEK directly regulates Lhx6 transcription or acts through NKX2.1 not distinguished
    • Relevance to neurofibromatosis-associated cognitive phenotypes not tested
  13. 2021 High

    Multiple studies resolved that Lhx6 controls Wnt signaling in dental root morphogenesis via Sfrp2 regulation, supports hypothalamic neuron survival rather than migration, and that distinct upstream factors (Nkx2-1, Nkx2-2, Dlx1/2) specify spatially segregated Lhx6+ hypothalamic neuron populations responsive to sleep pressure.

    Evidence Conditional Lhx6 KO with Wnt reporter and pathway rescue for dental; conditional KO with single-cell transcriptomics and sleep pressure assays for hypothalamus

    PMID:33479483 PMID:33596195

    Open questions at the time
    • Direct Lhx6 binding at Sfrp2 locus not demonstrated
    • Molecular effectors downstream of Lhx6 in hypothalamic neuron survival not identified
  14. 2022 High

    Two studies defined the temporal limits of LHX6 function: MTG8 was identified as a LHX6-interacting cofactor that together specify SST+/NPY+ interneuron identity before cortical entry, while postnatal deletion showed LHX6 is dispensable in mature PV+ interneurons, indicating its targets become independently maintained.

    Evidence Co-immunoprecipitation and in vivo subtype analysis for MTG8; adult conditional KO with electrophysiology and behavior for postnatal dispensability

    PMID:35318414 PMID:36064547

    Open questions at the time
    • How embryonic LHX6 targets are epigenetically locked in for postnatal maintenance unknown
    • Full repertoire of LHX6 transcriptional co-factors not catalogued
  15. 2024 Medium

    LHX6 deficiency in human palatal mesenchymal cells impairs mitophagy via the PINK1/Parkin pathway and activates MAPK signaling, suggesting a previously unrecognized role in mitochondrial quality control during palate development.

    Evidence siRNA knockdown and overexpression in human palatal cells, TEM, mitochondrial function assays, Western blot for PINK1/Parkin

    PMID:39438838

    Open questions at the time
    • Whether mitophagy regulation is a direct transcriptional effect of LHX6 or secondary unknown
    • Not replicated in vivo or by independent lab
    • Relevance to neuronal contexts not tested
  16. 2026 High

    Direct binding of LHX6 to the UGT8 promoter in breast cancer cells and functional consequences on galactosylceramide synthesis and drug sensitivity demonstrated a role for LHX6 in lipid metabolism gene regulation outside its canonical developmental context.

    Evidence SPR, EMSA, site-directed mutagenesis of LHX6 binding sites, dual-luciferase reporter, RNAi knockdown with apoptosis assay in MDA-MB-231 cells

    PMID:41781553

    Open questions at the time
    • Physiological relevance of LHX6-UGT8 axis in normal tissues unknown
    • Whether LHX6 is expressed endogenously at significant levels in breast epithelium not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The genome-wide direct target repertoire of LHX6 across tissues and developmental stages, the structural basis of its cofactor interactions, and the mechanisms by which its developmental targets become epigenetically maintained in adulthood remain unresolved.
  • No genome-wide ChIP-seq or CUT&RUN map of LHX6 binding across brain regions and developmental timepoints
  • No crystal/cryo-EM structure of LHX6 alone or in complex with cofactors
  • Mechanism of postnatal target maintenance after LHX6 becomes dispensable is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 3
Partners
ARXLDB1LHX8MTG8NKX2-1PITX2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Lhx6 expression in mandibular mesenchyme is regulated by epithelial-derived signals, and FGF8 is primarily responsible for restricting Lhx6 expression to the oral aspect of the maxillary and mandibular processes, as demonstrated by bead implantation experiments in vitro. Explant cultures, bead implantation experiments, whole-mount in situ hybridization Development Medium 9570771
1999 Lhx6.1 (an isoform of Lhx6) interacts with the LIM-domain binding protein Ldb1 through its tandem LIM-domains, suggesting transcriptional regulation of Lhx6 by Ldb1. Protein interaction assay (co-immunoprecipitation/pulldown) using tandem LIM-domains Journal of biochemistry Medium 10393337
2004 Silencing lhx6 by siRNA impedes tangential migration of interneurons from the MGE into the cortex but does not affect GABA production or its synthesizing enzyme (GAD), indicating Lhx6 controls migration but not GABAergic neurotransmitter identity. siRNA knockdown (U6 promoter-driven vector) in mouse embryonic brain slices and dissociated MGE cultures; GABA/GAD assay The Journal of neuroscience High 15201337
2005 Lhx6 marks neurons in the posterior medial amygdala that project to the ventromedial hypothalamus along the reproductive branch of the amygdala-hypothalamus pathway, defining a transcription factor-delineated circuit for innate reproductive behaviors. Genetically encoded and conventional axonal tracing, Lhx6-reporter expression analysis Neuron Medium 15944132
2007 Lhx6 is required for the specification of parvalbumin- and somatostatin-positive cortical interneuron subtypes in the neocortex and hippocampus, and for normal tangential and radial migration of GABAergic interneurons in the cortex. Lhx6 loss-of-function mouse genetics, immunofluorescence for interneuron subtype markers The Journal of neuroscience High 17376969
2008 NKX2.1 protein directly binds a highly conserved sequence in the Lhx6 promoter and activates Lhx6 transcription; Lhx6 is necessary and sufficient downstream of NKX2.1 to specify parvalbumin- and somatostatin-expressing cortical interneurons. Chromatin immunoprecipitation (ChIP), electroporation/transplantation rescue assay, gain- and loss-of-function in Nkx2.1-/- slice cultures Development High 18339674
2008 Lhx6 loss-of-function reveals distinct molecular pathways: Lhx6 promotes expression of interneuron migration receptors ErbB4, CXCR4, and CXCR7, and transcription factors Arx, bMaf, Cux2, and NPAS1 involved in interneuron development; parvalbumin+ and somatostatin+ interneurons fail to differentiate but NPY+ interneurons (from Lhx6-negative progenitors) are preserved. Lhx6 loss-of-function allele expressing PLAP, gene expression analysis in mutants The Journal of comparative neurology High 18613121
2009 Lhx6 and Lhx7 have redundant roles in craniofacial development: double-homozygous knockout mice lack molar teeth due to failure of molar mesenchyme specification, and show cleft palate and cranial skeleton defects, demonstrating overlapping functions in dentition patterning. Mouse double-knockout genetics, histology Developmental biology High 19591819
2011 Lhx6 and Lhx8 coexpression in early-born MGE neurons is required to induce neuronal Shh expression via regulation of a Shh enhancer; Shh signaling from MGE neurons non-cell-autonomously feeds back to promote the MGE progenitor developmental program and generation of late-born somatostatin+ and parvalbumin+ cortical interneurons. Mouse genetics (conditional Shh deletion in MGE mantle zone), reporter assays, gene expression analysis Neuron High 21658586
2012 LHX6 acts as a transcriptional repressor: it directly interacts with PITX2 homeodomain transcription factor in the nucleus, represses PITX2 transcriptional activity and activation of multiple promoters including the Lhx6 promoter itself, and inhibits PITX2 synergistic activation with LEF-1 and β-catenin. LHX6 represses amelogenin and ameloblastin expression and regulates cell proliferation and differentiation during odontogenesis. Chromatin immunoprecipitation (ChIP), bimolecular fluorescence complementation (BiFC), promoter reporter assays, Lhx6 null mouse analysis The Journal of biological chemistry High 23229549
2012 Reduced Lhx6 activity (hypomorphic allele) leads to widespread differentiation defects selectively in somatostatin+ interneurons (but not parvalbumin+ interneurons in most regions), reduced metabotropic glutamate receptor 1 expression, altered dendritic inhibition in CA1, and spontaneous seizures, establishing Lhx6 as required for interneuron maturation and functional inhibitory circuit formation. Hypomorphic Lhx6 allele mouse model, electrophysiology, EEG, immunofluorescence Cerebral cortex High 22710612
2014 Lhx6 directly binds in vivo to an Arx enhancer and an intronic CXCR7 enhancer; Arx and CXCR7 rescue divergent aspects of Lhx6-/- cell-fate and laminar position phenotypes respectively; Lhx6-/- MGE cells acquire a CGE-like fate. In vivo ChIP at enhancers, MGE complementation/transplantation assay, gene expression analysis Neuron High 24742460
2015 LHX6 and LHX8 negatively regulate the cell cycle inhibitor p57Kip2 (Cdkn1c) via both direct and indirect mechanisms (the latter mediated by FOX family transcription factors) to promote cell proliferation during palate development; this was demonstrated by ChIP, in silico motif analysis, and in vitro reporter assays. Chromatin immunoprecipitation, reporter assays, genome-wide transcriptional profiling in Lhx6/Lhx8 double-KO mice Human molecular genetics High 26071365
2015 The C. elegans LHX6 ortholog LIM-4 directly regulates terminal differentiation of cholinergic SMB neurons by binding cis-regulatory motifs of cholinergic gene battery and flp-12 neuropeptide genes; human LHX6 and LHX8 functionally substitute for LIM-4 in C. elegans, and human LHX6 can induce cholinergic and peptidergic characteristics in human neuronal cell lines. C. elegans genetics (lim-4 mutants), transcriptional reporter assays, cross-species functional complementation, human neuronal cell line assays PLoS genetics High 26305787
2017 Lhx6-positive GABAergic neurons in the ventral zona incerta directly inhibit wake-active hypocretin and GABAergic cells in the lateral hypothalamus; conditional deletion of Lhx6 from the developing diencephalon decreases both NREM and REM sleep; selective activation/inhibition of these neurons bidirectionally regulates sleep time in part through hypocretin-dependent mechanisms. Conditional Lhx6 deletion, optogenetic activation/inhibition, retrograde tracing, chemogenetics, EEG/EMG sleep recording Nature High 28847002
2020 Loss of Nf1 in MGE-derived cells leads to dose-dependent decrease in Lhx6 expression via a neurofibromin/Ras/MEK pathway; this is rescued by the MEK inhibitor SL327, identifying MEK signaling as a regulator of Lhx6 expression during cortical interneuron development. Conditional Nf1 deletion from MGE, MEK inhibitor rescue (SL327), gene expression analysis Proceedings of the National Academy of Sciences High 32123116
2021 Lhx6 labels root progenitor cells in the apical dental mesenchyme; loss of Lhx6 leads to furcation and root number defects; mechanistically, Lhx6 loss causes elevated Wnt antagonist Sfrp2 expression and down-regulation of Wnt signaling in the furcation region; overactivation of Wnt signaling in Lhx6+ cells partially restores furcation defects. Conditional Lhx6 KO, Wnt signaling reporter, Wnt pathway activation rescue, gene expression analysis PLoS genetics High 33596195
2021 In the hypothalamus, Lhx6 is necessary for neuronal survival (not migration), and distinct transcription factors Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons; Nkx2-2+/Lhx6+ neurons in the zona incerta are responsive to sleep pressure. Conditional KO mouse genetics, single-cell transcriptomics, sleep pressure assays, cell survival analysis Communications biology High 33479483
2022 MTG8 (a conserved transcriptional co-factor) interacts with LHX6, and together the two factors are sufficient to promote expression of critical cortical interneuron subtype identity genes for a large subset of SST+/NPY+ MGE-derived interneurons; this SST-NPY fate is initiated early before interneurons migrate into the cortex. Co-immunoprecipitation/interaction assay, in vivo functional studies, interneuron subtype marker analysis in MTG8 mutants Nature communications High 36064547
2022 Postnatal removal of Lhx6 in mature parvalbumin-positive hippocampal interneurons (>8 weeks) does not affect interneuron number, morphology, physiology, or cognitive behavior, indicating Lhx6 is dispensable for mature interneuron maintenance and that its embryonic downstream targets (Sox6, Arx) become uncoupled from Lhx6 postnatally. Viral and transgenic Cre-mediated conditional KO in adult Lhx6loxP/loxP mice, electrophysiology, behavior assays Scientific reports High 35318414
2024 Lhx6 deficiency in human embryonic palatal mesenchymal cells causes mitophagy dysfunction via the PINK1/Parkin pathway and activates MAPK signaling, impairing cell proliferation and migration; overexpression of Lhx6 restores mitochondrial homeostasis and rescues retinoic acid-induced dysfunction. siRNA knockdown and overexpression, transmission electron microscopy, mitochondrial function assays (MitoTracker, ROS, ATP, mtDNA), Western blot for PINK1/Parkin pathway components Molecular medicine Medium 39438838
2026 LHX6 binds directly to two binding sites (LHX6BS2 being essential) in the UGT8 promoter response element in breast cancer cells; RNAi-mediated inhibition of LHX6 reduces UGT8 expression and galactosylceramide synthesis, sensitizing MDA-MB-231 cells to doxorubicin-induced apoptosis. Dual-luciferase reporter assay, EMSA, site-directed mutagenesis, surface plasmon resonance (LHX6-DNA interaction), RNAi knockdown, apoptosis assay Scientific reports High 41781553

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus. Neuron 377 15944132
2007 Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes. The Journal of neuroscience : the official journal of the Society for Neuroscience 317 17376969
1998 Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development. Development (Cambridge, England) 259 9570771
2008 NKX2.1 specifies cortical interneuron fate by activating Lhx6. Development (Cambridge, England) 177 18339674
2017 Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep. Nature 175 28847002
2008 Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants. The Journal of comparative neurology 171 18613121
2011 Lhx6 and Lhx8 coordinately induce neuronal expression of Shh that controls the generation of interneuron progenitors. Neuron 124 21658586
2004 Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience 119 15201337
2014 Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and laminar position. Neuron 100 24742460
2009 The LIM homeodomain transcription factors Lhx6 and Lhx7 are key regulators of mammalian dentition. Developmental biology 53 19591819
2012 The LIM homeodomain protein Lhx6 regulates maturation of interneurons and network excitability in the mammalian cortex. Cerebral cortex (New York, N.Y. : 1991) 52 22710612
2021 Placental trophoblast cell-derived exosomal microRNA-1290 promotes the interaction between endometrium and embryo by targeting LHX6. Molecular therapy. Nucleic acids 50 34729246
2013 LHX6 acts as a novel potential tumour suppressor with epigenetic inactivation in lung cancer. Cell death & disease 47 24157876
2017 Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression. Scientific reports 44 28396596
2018 MiR-1290 promotes proliferation, migration, and invasion of glioma cells by targeting LHX6. Journal of cellular physiology 43 29226322
2006 LHX6 is a sensitive methylation marker in head and neck carcinomas. Oncogene 43 16732332
2015 Lhx6 and Lhx8: cell fate regulators and beyond. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 40 26148970
2019 Epigenetic inactivation of LHX6 mediated microcystin-LR induced hepatocarcinogenesis via the Wnt/β-catenin and P53 signaling pathways. Environmental pollution (Barking, Essex : 1987) 37 31151060
2021 Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons. Communications biology 30 33479483
2019 Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6. Cancers 30 31810245
2015 LHX6 inhibits breast cancer cell proliferation and invasion via repression of the Wnt/β-catenin signaling pathway. Molecular medicine reports 28 26129710
2012 The LIM homeodomain transcription factor LHX6: a transcriptional repressor that interacts with pituitary homeobox 2 (PITX2) to regulate odontogenesis. The Journal of biological chemistry 28 23229549
2015 Lhx6 and Lhx8 promote palate development through negative regulation of a cell cycle inhibitor gene, p57Kip2. Human molecular genetics 23 26071365
2014 Cortical inhibitory neuron disturbances in schizophrenia: role of the ontogenetic transcription factor Lhx6. Schizophrenia bulletin 23 24837792
2011 Epigenetic regulation of the potential tumor suppressor gene, hLHX6.1, in human cervical cancer. International journal of oncology 20 21240459
1999 A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains. Journal of biochemistry 20 10393337
2015 The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type. PLoS genetics 19 26305787
2002 Comparison of the expression patterns of two LIM-homeodomain genes, Lhx6 and L3/Lhx8, in the developing palate. Orthodontics & craniofacial research 19 12086327
2020 Nf1 deletion results in depletion of the Lhx6 transcription factor and a specific loss of parvalbumin+ cortical interneurons. Proceedings of the National Academy of Sciences of the United States of America 18 32123116
2020 LHX6 Affects Erlotinib Resistance and Migration of EGFR-Mutant Non-Small-Cell Lung Cancer HCC827 Cells Through Suppressing Wnt/β-Catenin Signaling. OncoTargets and therapy 18 33149613
2010 The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer. Oncology reports 18 20428825
2021 Lhx6 regulates canonical Wnt signaling to control the fate of mesenchymal progenitor cells during mouse molar root patterning. PLoS genetics 16 33596195
2020 Targeted recombination in active populations as a new mouse genetic model to study sleep-active neuronal populations: Demonstration that Lhx6+ neurons in the ventral zona incerta are activated during paradoxical sleep hypersomnia. Journal of sleep research 16 31943457
2024 Specific transcription factors Ascl1 and Lhx6 attenuate diabetic neuropathic pain by modulating spinal neuroinflammation and microglial activation in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 38479183
2022 MTG8 interacts with LHX6 to specify cortical interneuron subtype identity. Nature communications 14 36064547
2020 Association of Genetic Variation in the 3'UTR of LHX6, IMMP2L, and AADAC With Tourette Syndrome. Frontiers in neurology 13 32922348
2012 Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome. Genes, brain, and behavior 13 22435649
2018 LHX6 inhibits the proliferation, invasion and migration of breast cancer cells by modulating the PI3K/Akt/mTOR signaling pathway. European review for medical and pharmacological sciences 12 29863252
2022 The development of MGE-derived cortical interneurons: An Lhx6 tale. The International journal of developmental biology 10 34881792
2022 Hsa_circ_0008726 regulates the proliferation, migration, and invasion of trophoblast cells in preeclampsia through modulating the miR-1290-LHX6 signaling pathway. Journal of clinical laboratory analysis 10 35698314
2018 Downregulation of tumor-suppressor gene LHX6 in cancer: a systematic review. Romanian journal of internal medicine = Revue roumaine de medecine interne 9 29533904
2024 Lhx6 deficiency causes human embryonic palatal mesenchymal cell mitophagy dysfunction in cleft palate. Molecular medicine (Cambridge, Mass.) 8 39438838
2022 The exon 12-containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway. Cancer medicine 7 35384355
2020 Methylation-mediated silencing of the LIM homeobox 6 (LHX6) gene promotes cell proliferation in human pancreatic cancer. Biochemical and biophysical research communications 7 32248980
2021 Tumor suppressor LHX6 upregulation contributes to the inhibitory effect of miR-346 knockdown on colorectal cancer cell growth. Environmental toxicology 6 34773443
2021 The conserved core of the nereid brain: Circular CNS, apical nervous system and lhx6-arx-dlx neurons. Current opinion in neurobiology 5 34861534
2022 The impact of glutamine deprivation on the expression of MEIS3, SPAG4, LHX1, LHX2, and LHX6 genes in ERN1 knockdown U87 glioma cells. Endocrine regulations 4 35180817
2022 A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons. Cells 4 35269475
2022 Interneuron function and cognitive behavior are preserved upon postnatal removal of Lhx6. Scientific reports 4 35318414
2021 Candidate positive targets of LHX6 and LHX8 transcription factors in the developing upper jaw. Gene expression patterns : GEP 3 34861428
2024 Knockdown of Lhx6 during embryonic development results in neurophysiological alterations and behavioral deficits analogous to schizophrenia in adult rats. Schizophrenia research 2 38531158
2024 Modulation of pain sensitivity by Ascl1- and Lhx6-dependent GABAergic neuronal function in streptozotocin diabetic mice. Molecular therapy : the journal of the American Society of Gene Therapy 2 39741412
2019 Expression of Lhx6 in the adult and developing mouse retina. Gene expression patterns : GEP 2 31376504
2026 Comparative distribution of the hypothalamic neurons activated during wakefulness and paradoxical (REM) sleep using male TRAP2-red mice: contribution of orexin, MCH, Lhx6, and a new marker Meis2. Sleep 1 41313264
2025 FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma. Cancer research 1 39495206
2022 LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF. Journal of developmental origins of health and disease 1 36154949
2021 Erratum: LHX6 Affects Erlotinib Resistance and Migration of EGFR-Mutant Non-Small-Cell Lung Cancer HCC827 Cells Through Suppressing Wnt/β-Catenin Signaling [Corrigendum]. OncoTargets and therapy 1 33469305
2026 UGT8/GalCer-dependent resistance of breast cancer cells to drug-induced apoptosis is potentially regulated by the LIM/homeobox protein LHX6. Scientific reports 0 41781553
2021 Erratum: LHX6 Affects Erlotinib Resistance and Migration of EGFR-Mutant Non-Small-Cell Lung Cancer HCC827 Cells Through Suppressing Wnt/β-Catenin Signaling [Corrigendum]. OncoTargets and therapy 0 33854331