Affinage

LHX6

LIM/homeobox protein Lhx6 · UniProt Q9UPM6

Length
363 aa
Mass
40.0 kDa
Annotated
2026-06-10
59 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LHX6 is a LIM-homeodomain transcription factor that functions as a master regulator of GABAergic interneuron development from the medial ganglionic eminence (MGE) (PMID:17376969, PMID:18613121). Its expression is directly activated by NKX2.1, which binds a conserved element in the Lhx6 promoter, and LHX6 is necessary and sufficient downstream of NKX2.1 to specify parvalbumin- and somatostatin-expressing cortical interneuron subtypes (PMID:18339674); this requirement is restricted to early development, as postnatal removal in mature parvalbumin interneurons has no phenotypic consequence (PMID:35318414). LHX6 directs interneuron fate by binding enhancers of downstream targets including Arx and an intronic CXCR7 element, with Arx rescuing cell-fate defects and CXCR7 rescuing laminar positioning in Lhx6-null MGE cells, which otherwise acquire a CGE-like fate (PMID:24742460); it also induces migration receptors ErbB4, CXCR4, and CXCR7 to drive tangential migration into the cortex without affecting GABA/GAD expression (PMID:15201337, PMID:18613121). Together with LHX8 it activates a neuronal Shh enhancer, establishing a non-autonomous feedback loop that sustains MGE progenitor identity (PMID:21658586). LHX6 acts mechanistically as a transcriptional repressor and assembles with co-factors: it binds the LIM-domain binding protein LDB1 through its tandem LIM domains (PMID:10393337), interacts with PITX2 to repress its transcriptional activity (PMID:23229549), and partners with the co-factor MTG8 to specify SST-NPY interneuron identity (PMID:36064547). Beyond the telencephalon, LHX6 is required for the survival of hypothalamic GABAergic neurons (PMID:33479483), and Lhx6+ neurons of the ventral zona incerta promote sleep by directly inhibiting wake-active hypocretin neurons (PMID:28847002). In craniofacial development LHX6 (with LHX8) directly regulates targets such as Eya1, Barx1, and Rspo2/3 and represses the cell-cycle inhibitor p57Kip2 to control palate and tooth root development (PMID:26071365, PMID:33596195, PMID:34861428). In cancer, LHX6 acts as a tumor suppressor that restrains proliferation, migration, and Wnt/β-catenin signaling (PMID:24157876, PMID:33149613), yet in breast cancer cells it directly activates UGT8 transcription to drive galactosylceramide synthesis and chemoresistance (PMID:41781553).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 Medium

    Established that Lhx6 expression in craniofacial mesenchyme is controlled by epithelial signaling, placing the gene downstream of FGF8 in branchial-arch patterning.

    Evidence FGF8-soaked bead implantation in oral mesenchyme explants with whole-mount in situ hybridization

    PMID:9570771

    Open questions at the time
    • Does not define direct transcriptional targets of LHX6 in this tissue
    • Mechanism linking FGF8 signaling to the Lhx6 locus not resolved
  2. 1999 Medium

    Identified LDB1 as a physical cofactor binding the tandem LIM domains, providing the first molecular handle on how LHX6 activity is regulated through protein interaction.

    Evidence Co-immunoprecipitation/pulldown mapping interaction to the tandem LIM domains

    PMID:10393337

    Open questions at the time
    • Functional consequence of LDB1 binding on target genes not tested
    • Single method, single lab
  3. 2004 High

    Separated migration from neurotransmitter specification, showing LHX6 is required for tangential MGE-to-cortex migration but not for GABA production.

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

    PMID:15201337

    Open questions at the time
    • Migration receptors mediating the effect not yet identified
    • Acute knockdown does not address fate specification roles
  4. 2007 High

    Genetic knockout established LHX6 as required for parvalbumin and somatostatin interneuron specification and cortical migration, defining its developmental phenotype.

    Evidence Lhx6 knockout mice with PV/SST/calretinin immunostaining and migration analysis

    PMID:17376969

    Open questions at the time
    • Direct transcriptional targets not defined
    • Does not address upstream regulators
  5. 2008 High

    Positioned LHX6 in the NKX2.1 transcriptional cascade as a necessary-and-sufficient effector, and defined the migration-receptor and transcription-factor targets it induces.

    Evidence ChIP of NKX2.1 at the Lhx6 promoter, Nkx2.1-/- rescue by Lhx6, and a PLAP knock-in loss-of-function allele with marker and gene-expression analysis

    PMID:18339674 PMID:18613121

    Open questions at the time
    • Direct vs indirect regulation of ErbB4/CXCR4/CXCR7 not all distinguished
    • Mechanism of subtype divergence (PV vs SST vs NPY) unresolved
  6. 2011 High

    Revealed a non-autonomous Shh feedback loop in which LHX6/LHX8 activate a neuronal Shh enhancer to sustain progenitor identity and late interneuron production.

    Evidence Conditional Shh deletion, Lhx6/Lhx8 double mutants, and in vivo Shh enhancer reporter assays

    PMID:21658586

    Open questions at the time
    • Direct LHX6 binding to the Shh enhancer not shown in this study
    • Quantitative contribution of feedback vs autonomous regulation unclear
  7. 2012 High

    Defined LHX6 as a transcriptional repressor that physically interacts with PITX2 and uncovered a somatostatin-selective requirement whose loss causes circuit-level seizure phenotypes.

    Evidence BiFC, ChIP, co-IP and luciferase assays for PITX2 interaction/repression; hypomorphic allele with electrophysiology and EEG

    PMID:22710612 PMID:23229549

    Open questions at the time
    • Repression-complex composition beyond PITX2 not defined
    • How dose-sensitivity selectively affects SST neurons unresolved
  8. 2014 High

    Demonstrated direct in vivo enhancer binding to Arx and CXCR7 with functional rescue, mechanistically separating fate specification from laminar positioning.

    Evidence In vivo ChIP at Arx and CXCR7 enhancers and MGE complementation/transplantation rescue assays

    PMID:24742460

    Open questions at the time
    • Full enhancer target catalog not defined
    • Cofactor requirements at these enhancers not characterized
  9. 2015 Medium

    Extended LHX6 function to craniofacial development, showing it represses the cell-cycle inhibitor p57Kip2 to permit palatal proliferation, and that human LHX6 is functionally conserved with the C. elegans ortholog LIM-4.

    Evidence Lhx6/Lhx8 double knockout with ChIP and reporter assays; cross-species genetic complementation in C. elegans lim-4 mutants

    PMID:26071365 PMID:26305787

    Open questions at the time
    • Direct vs FOX-mediated regulation of p57Kip2 not fully separated
    • Conserved direct targets in C. elegans not mapped
  10. 2017 High

    Identified an adult circuit function: Lhx6+ zona incerta GABAergic neurons promote sleep by directly inhibiting wake-active hypocretin neurons.

    Evidence Conditional Lhx6 knockout, chemogenetic bidirectional manipulation, retrograde tracing, polysomnography and electrophysiology

    PMID:28847002

    Open questions at the time
    • Transcriptional targets underlying ZI neuron function not defined
    • Whether LHX6 acts developmentally or in mature circuit maintenance not fully separated
  11. 2020 Medium

    Placed LHX6 expression downstream of neurofibromin/Ras/MEK signaling, and independently established a tumor-suppressive role via Wnt/β-catenin inhibition in lung cancer.

    Evidence Conditional Nf1 deletion with MEK-inhibitor rescue; CRISPR knockout and overexpression with TCF/LEF reporter and migration assays in NSCLC

    PMID:32123116 PMID:33149613

    Open questions at the time
    • Direct vs indirect Wnt pathway regulation not resolved
    • Whether the same target genes operate in development and cancer unknown
  12. 2021 Medium

    Refined LHX6 roles across tissues: survival of hypothalamic GABAergic neurons (distinct from migratory cortical interneurons), tooth root patterning via Wnt, and direct enhancer regulation of upper-jaw target genes.

    Evidence Conditional knockouts with scRNA-seq, Wnt epistasis rescue, and ChIP plus expression profiling in pharyngeal arch

    PMID:33479483 PMID:33596195 PMID:34861428

    Open questions at the time
    • Why hypothalamic Lhx6 neurons require it for survival rather than migration unexplained
    • Direct vs indirect control of Wnt antagonist Sfrp2 not resolved
  13. 2022 Medium

    Identified MTG8 as a sufficient cofactor for early SST-NPY fate initiation, and showed LHX6 becomes uncoupled from downstream effectors in adult interneurons.

    Evidence Reciprocal co-IP and gain/loss-of-function with scRNA-seq; postnatal conditional knockout with cellular, physiological and behavioral readouts

    PMID:35318414 PMID:36064547

    Open questions at the time
    • Mechanism of developmental-stage-specific uncoupling unknown
    • Structural basis of LHX6-MTG8 interaction undefined
  14. 2024 Medium

    Linked LHX6 to mitochondrial homeostasis in palatal mesenchyme via PINK1/Parkin mitophagy and MAPK signaling.

    Evidence Knockdown/overexpression in HEPM cells with mitochondrial function assays, electron microscopy and PINK1/Parkin Western blots

    PMID:39438838

    Open questions at the time
    • Whether LHX6 directly regulates mitophagy genes transcriptionally not shown
    • Relevance of cell-line findings to in vivo palate development not established
  15. 2026 Medium

    Demonstrated a context-dependent activating role: LHX6 directly binds and activates the UGT8 promoter to drive galactosylceramide synthesis and chemoresistance in breast cancer, contrasting with its repressive/tumor-suppressive activity elsewhere.

    Evidence Promoter deletion and mutagenesis reporter assays, EMSA, surface plasmon resonance, RNAi, TLC and apoptosis assays

    PMID:41781553

    Open questions at the time
    • What determines repressor vs activator behavior across contexts unresolved
    • Cofactors enabling activation at UGT8 not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LHX6 switches between transcriptional repression and activation across tissues, and the full cofactor/enhancer logic governing context-specific target selection, remain unresolved.
  • No structural model of LHX6 on its target enhancers in different contexts
  • Determinants of repressor vs activator output not defined
  • Comprehensive genome-wide direct target map across tissues lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-112316 Neuronal System 1
Partners
LDB1LHX8MTG8NKX2.1PITX2

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 LHX6.1 (an isoform of LHX6) physically interacts with the LIM-domain binding protein Ldb1 through its tandem LIM-domains, implicating Ldb1 in transcriptional regulation of LHX6.1 activity. Protein-protein interaction assay (co-immunoprecipitation/pulldown) demonstrating interaction between Lhx6.1 and Ldb1 via tandem LIM-domains Journal of biochemistry Medium 10393337
1998 FGF8 signaling from the overlying epithelium is required for the restricted expression of Lhx6 and Lhx7 in the oral mesenchyme of the maxillary and mandibular processes; bead implantation of FGF8 in explant cultures induced ectopic expression. Explant cultures with bead implantation (FGF8-soaked beads), whole-mount in situ hybridisation Development (Cambridge, England) Medium 9570771
2004 Loss of Lhx6 function (via siRNA) impedes tangential migration of interneurons from the MGE into the cortex but does not block their dispersion within the ganglionic eminence, and does not affect GABA production or GAD expression, indicating Lhx6 is specifically required for migration but not neurotransmitter phenotype specification. siRNA knockdown (U6-driven vector) in mouse embryonic brain slices and dissociated MGE neuronal cultures; GABA/GAD immunostaining The Journal of neuroscience : the official journal of the Society for Neuroscience High 15201337
2007 Lhx6 is required for specification of parvalbumin- and somatostatin-expressing cortical interneuron subtypes in the neocortex and hippocampus, and is also required for normal tangential and radial migration of GABAergic interneurons into the cortex. Genetic loss-of-function (Lhx6 knockout mice); immunostaining for PV, SST, calretinin; analysis of migration patterns The Journal of neuroscience : the official journal of the Society for Neuroscience High 17376969
2008 NKX2.1 protein directly binds a highly conserved sequence in the Lhx6 promoter to activate Lhx6 transcription; Lhx6 is necessary and sufficient downstream of NKX2.1 to rescue PV- and SST-expressing cortical interneuron specification in Nkx2.1-/- MGE cells. Electroporation of Nkx2.1 cDNA into Nkx2.1-/- slice cultures, transplantation into neonatal cortex; gain- and loss-of-function for Lhx6; chromatin immunoprecipitation (ChIP) of NKX2.1 at the Lhx6 promoter Development (Cambridge, England) High 18339674
2008 Lhx6 loss-of-function leads to migration defects preferentially affecting the marginal zone and superficial neocortical plate, failure of parvalbumin+ and somatostatin+ interneuron differentiation (while NPY+ interneurons remain from an Lhx6-;Dlx+ subtype), and distinct striatal interneuron deficits. Lhx6 mediates these effects through promoting expression of migration receptors ErbB4, CXCR4, and CXCR7, and transcription factors Arx, bMaf, Cux2, and NPAS1. Lhx6 loss-of-function allele (PLAP knock-in); immunostaining for PV, SST, NPY; analysis of migration and gene expression The Journal of comparative neurology High 18613121
2011 Lhx6 and Lhx8 together are required in early-born MGE neurons to induce neuronal Shh expression by regulating a Shh enhancer; this Shh expression feeds back non-autonomously to the overlying progenitor zone to sustain Lhx6, Lhx8, and Nkx2-1 expression and promote generation of late-born somatostatin+ and parvalbumin+ cortical interneurons. Conditional genetic deletion of Shh in MGE mantle zone; Lhx6/Lhx8 double mutant analysis; in vivo reporter assays for Shh enhancer activity Neuron High 21658586
2012 LHX6 acts as a transcriptional repressor; it directly interacts with PITX2 homeodomain transcription factor in the nucleus (shown by bimolecular fluorescence complementation), represses the Lhx6 promoter activity, and inhibits PITX2-mediated transcriptional activation of multiple downstream targets including those involved in odontogenesis. Endogenous PITX2 binds the Lhx6 promoter (shown by ChIP). Luciferase reporter assay, bimolecular fluorescence complementation (BiFC), chromatin immunoprecipitation (ChIP), co-immunoprecipitation, analysis of Lhx6 null mice The Journal of biological chemistry High 23229549
2012 Reduced Lhx6 activity (hypomorphic allele) selectively impairs differentiation of somatostatin+ interneurons without affecting interneuron number or migration; this leads to reduced mGluR1 expression in CA1 stratum oriens, defective dendritic inhibition of CA1 pyramidal cells, and recurrent seizure activity in adult mice. Hypomorphic Lhx6 allele; immunostaining; electrophysiology; EEG recordings; behavioral analysis Cerebral cortex (New York, N.Y. : 1991) High 22710612
2014 Lhx6 directly binds in vivo to an Arx enhancer and to an intronic CXCR7 enhancer; Arx rescues cell-fate defects and CXCR7 rescues laminar positioning defects in Lhx6-/- MGE cells in an in vivo complementation/transplantation assay. Lhx6-/- MGE cells acquire a CGE-like fate. In vivo MGE complementation/transplantation assay; ChIP for LHX6 binding at Arx and CXCR7 enhancers; gain-of-function rescue experiments Neuron High 24742460
2015 LHX6 and LHX8 negatively regulate p57Kip2 (Cdkn1c, a cell cycle inhibitor) in the prospective palate to allow adequate cell proliferation for normal palate development. LHX6 and LHX8 bind directly to cis-regulatory elements near p57Kip2, and also regulate p57Kip2 indirectly through Forkhead box (FOX) family transcription factors. Lhx6/Lhx8 double knockout; genome-wide transcriptional profiling; chromatin immunoprecipitation; in vitro luciferase reporter assays with putative cis-regulatory elements Human molecular genetics High 26071365
2015 The C. elegans ortholog LIM-4 and human LHX6 are functionally conserved; human LHX6 (and LHX8) can functionally substitute for LIM-4 in C. elegans to restore SMB neuron terminal differentiation gene expression, and C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in human neuronal cell lines. Genetic complementation in C. elegans lim-4 mutants; expression of human LHX6 in C. elegans; expression in human neuronal cell lines with reporter assays PLoS genetics Medium 26305787
2017 Lhx6-positive GABAergic neurons in the ventral zona incerta directly inhibit wake-active hypocretin and GABAergic neurons in the lateral hypothalamus; conditional deletion of Lhx6 from the developing diencephalon decreases both NREM and REM sleep; selective chemogenetic activation and inhibition of Lhx6+ ZI neurons bidirectionally regulates sleep time through hypocretin-dependent mechanisms. Conditional Lhx6 knockout; optogenetics/chemogenetics (DREADDs); retrograde tracing; polysomnography; electrophysiology Nature High 28847002
2020 Loss of Nf1 in MGE-derived neurons results in a dose-dependent decrease in Lhx6 expression through a neurofibromin/Ras/MEK pathway; this is rescued by the MEK inhibitor SL327, identifying a signaling pathway that regulates LHX6 expression during cortical interneuron development. Conditional Nf1 deletion from MGE; pharmacological MEK inhibition (SL327); qPCR and immunostaining for Lhx6, PV, SST Proceedings of the National Academy of Sciences of the United States of America Medium 32123116
2021 Lhx6 is necessary for the survival of hypothalamic GABAergic neurons; Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons. Hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuron markers like Pvalb, distinguishing them from telencephalic Lhx6 interneurons. Conditional knockout of Lhx6 from developing diencephalon; genetic deletion of upstream transcription factors (Dlx1/2, Nkx2-2, Nkx2-1); immunostaining; single-cell transcriptomics Communications biology Medium 33479483
2021 Lhx6 labels root progenitor cells and regulates molar root patterning by controlling odontoblast fate commitment in a cell-autonomous manner. Lhx6 loss elevates expression of Wnt antagonist Sfrp2 and reduces Wnt signaling in the furcation region; overactivation of Wnt signaling in Lhx6+ progenitor cells partially restores furcation defects in Lhx6-/- mice. Lhx6 conditional knockout; Wnt pathway gain-of-function in Lhx6+ cells; RNA in situ hybridization; immunostaining PLoS genetics Medium 33596195
2021 LHX6 and LHX8 directly bind to enhancers near positive target genes Eya1, Barx1, Rspo2, Rspo3, and Wnt11 in the developing upper jaw first pharyngeal arch, as demonstrated by ChIP, and these genes are downregulated in Lhx6;Lhx8 mutants. Chromatin immunoprecipitation (ChIP) for LHX6 binding; RNA in situ hybridization in Lhx6;Lhx8 mutants; genome-wide transcriptional profiling Gene expression patterns : GEP Medium 34861428
2022 MTG8, a conserved transcriptional co-factor, physically interacts with LHX6 and together the two factors are sufficient to promote expression of cortical interneuron subtype identity genes, specifying an SST-NPY interneuron fate that is initiated early before interneurons migrate into the cortex. Co-immunoprecipitation of MTG8 and LHX6; gain-of-function co-expression; loss-of-function analysis; scRNA-seq for subtype identity Nature communications Medium 36064547
2022 Postnatal removal of Lhx6 in adult parvalbumin-positive hippocampal interneurons (using viral or transgenic Cre) does not affect PVI number, morphological or physiological properties, or cognitive behavior; loss of Lhx6 only partially reduces downstream transcription factors Sox6 and Arx, indicating Lhx6 becomes functionally uncoupled from its downstream effectors after early development. Conditional postnatal Lhx6 knockout (Lhx6loxP/loxP with viral/transgenic Cre); immunostaining; electrophysiology; behavioral assays Scientific reports Medium 35318414
2013 LHX6 acts as a tumor suppressor in lung cancer; forced expression of LHX6 suppresses cell viability, colony formation, migration, induces apoptosis and G1/S arrest, and inhibits tumorigenicity in nude mice. These effects are associated with upregulation of p21 and p53 and downregulation of Bcl-2, cyclinD1, c-myc, CD44, and MMP7. Forced expression and RNAi knockdown in lung cancer cell lines; colony formation, apoptosis, cell cycle assays; xenograft in nude mice; Western blot for downstream effectors Cell death & disease Medium 24157876
2020 LHX6 mediates erlotinib resistance and migration in NSCLC cells via the Wnt/β-catenin pathway; LHX6 knockout increases TCF/LEF reporter activity and β-catenin expression, while LHX6 overexpression suppresses Wnt/β-catenin signaling. LHX6 knockout (CRISPR-Cas9) and overexpression; TCF/LEF luciferase reporter assay; Western blot for β-catenin and Cyclin D1; transwell migration assay OncoTargets and therapy Medium 33149613
2024 Lhx6 maintains mitochondrial homeostasis in embryonic palatal mesenchymal cells via PINK1/Parkin-mediated mitophagy and MAPK signaling; knockdown of Lhx6 impairs mitochondrial function, proliferation and migration in HEPM cells, while Lhx6 overexpression rescues RA-induced mitochondrial dysfunction. Lhx6 knockdown and overexpression in HEPM cells; CCK-8, EdU, wound healing and transwell assays; MitoTracker, ROS measurement, ATP quantification, mtDNA copy number; Western blot for PINK1/Parkin pathway; transmission electron microscopy Molecular medicine (Cambridge, Mass.) Medium 39438838
2026 LHX6 transcriptionally activates UGT8 expression in breast cancer cells by binding to a specific regulatory element (LHX6BS2) within the UGT8 promoter; RNAi-mediated inhibition of LHX6 reduces UGT8 expression and galactosylceramide synthesis, sensitizing cells to doxorubicin-induced apoptosis. Dual-luciferase reporter assay with UGT8 promoter deletion constructs and site-directed mutagenesis; electrophoretic mobility shift assay (EMSA); surface plasmon resonance for LHX6-DNA interaction; RNAi knockdown; TLC for GalCer measurement; apoptosis assay Scientific reports Medium 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 379 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 320 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) 261 9570771
2017 Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep. Nature 178 28847002
2008 NKX2.1 specifies cortical interneuron fate by activating Lhx6. Development (Cambridge, England) 178 18339674
2008 Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants. The Journal of comparative neurology 172 18613121
2011 Lhx6 and Lhx8 coordinately induce neuronal expression of Shh that controls the generation of interneuron progenitors. Neuron 127 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 102 24742460
2009 The LIM homeodomain transcription factors Lhx6 and Lhx7 are key regulators of mammalian dentition. Developmental biology 54 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 48 24157876
2017 Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression. Scientific reports 45 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 41 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) 38 31151060
2021 Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons. Communications biology 31 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
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 19 33149613
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
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 17 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 17 31943457
2022 MTG8 interacts with LHX6 to specify cortical interneuron subtype identity. Nature communications 15 36064547
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
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
2022 The development of MGE-derived cortical interneurons: An Lhx6 tale. The International journal of developmental biology 12 34881792
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 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
2020 Methylation-mediated silencing of the LIM homeobox 6 (LHX6) gene promotes cell proliferation in human pancreatic cancer. Biochemical and biophysical research communications 8 32248980
2022 The exon 12-containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway. Cancer medicine 7 35384355
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 6 34861534
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 4 39741412
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
2025 FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma. Cancer research 2 39495206
2024 Knockdown of Lhx6 during embryonic development results in neurophysiological alterations and behavioral deficits analogous to schizophrenia in adult rats. Schizophrenia research 2 38531158
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
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

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