Affinage

LHX2

LIM/homeobox protein Lhx2 · UniProt P50458

Length
406 aa
Mass
44.4 kDa
Annotated
2026-06-14
100 papers in source corpus 64 papers cited in narrative 64 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LHX2 is a LIM-homeodomain transcription factor that functions as a master selector and progenitor-maintenance regulator across multiple developing tissues, cell-autonomously specifying cortical, retinal, olfactory, hepatic, and hair follicle stem-cell identity while suppressing alternative fates (PMID:9247336, PMID:18202285, PMID:23884928). Structurally it carries two LIM domains and a homeodomain (PMID:7678338), and it binds DNA directly through the homeodomain at AATT-core/(G/T)CAAT(T/A) consensus sites in target enhancers and promoters (PMID:17446187, PMID:22134063, PMID:15173589). LHX2 assembles into the conserved tetrameric LHX:LDB complex with LDB1, an interaction required for hippocampal fate and regional identity (PMID:32994168), and accessory factors—SSBP3 stabilizes and recruits the Lhx2-Ldb1 DNA-binding complex to target promoters (PMID:18565323), while LHX2 partners with OTX2 and the LDB1/SWI-SNF(BAF) module to set the retinal pigmented epithelium transcriptome (PMID:36649236) and engages NuRD subunits (LSD1, HDAC2, RBBP4) to repress chromatin at cortical fate genes such as Fezf2 and Sox11 (PMID:28053041). The protein also represses partner transcription factors non-transcriptionally: it binds Msx1 and c-Fos through homeodomain-containing regions in a manner mutually exclusive with their DNA binding, inhibiting c-Fos-driven NFATc1 transactivation during osteoclastogenesis (PMID:9697309, PMID:24902903), and displaces LMO2 from LDB1 to drive its proteasomal degradation in hematopoietic and T-ALL cells (PMID:23922318, PMID:29278703). Functionally, LHX2 maintains progenitor self-renewal and competence by gating Notch (Hes1/Hes5), Wnt/β-catenin, BMP, Shh (via Cdon/Gas1), and FGF signaling, and by directly regulating downstream targets including Pax6, Six6, Rax, Robo1/2, and odorant-receptor and OR-cluster super-enhancer assembly (PMID:26371318, PMID:26911688, PMID:36459481, PMID:19906857, PMID:19146846, PMID:22457488, PMID:30626972). Its loss produces defined developmental defects spanning anophthalmia, cortical and hippocampal hypoplasia, olfactory and hair-follicle failure, liver fibrosis, and pituitary defects (PMID:9247336, PMID:11165475, PMID:15536133, PMID:19900438), and germline LHX2 missense variants cause a loss-of-function neurodevelopmental disorder through impaired DNA binding, LDB1 interaction, or transactivation (PMID:37057675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 Medium

    Established the molecular identity of LHX2 as a LIM-homeodomain transcription factor, defining the structural modules (two LIM domains, one homeodomain) that would later explain its dual DNA-binding and protein-protein-interaction activities.

    Evidence cDNA cloning and sequence analysis

    PMID:7678338

    Open questions at the time
    • No functional assay of DNA binding or partner interaction in this initial study
    • No tissue function defined
  2. 1997 High

    Defined LHX2 as essential for organogenesis by showing germline loss causes anophthalmia, cortical hypoplasia, and anemia, distinguishing cell-autonomous (eye, forebrain) from non-autonomous (erythropoiesis) requirements.

    Evidence targeted germline knockout mouse with histology and embryo phenotyping

    PMID:9247336

    Open questions at the time
    • Did not identify direct transcriptional targets
    • Mechanism of non-autonomous erythropoietic requirement unresolved
  3. 1998 High

    Revealed a non-DNA-binding mode of action: LHX2 sequesters Msx1 via homeodomain-region contacts mutually exclusive with DNA binding, showing LHX2 can regulate partners by direct protein interaction independent of its own promoter occupancy.

    Evidence in vitro binding, cellular-extract pull-down, and EMSA competition

    PMID:9697309

    Open questions at the time
    • In vivo relevance of the Msx1 sequestration not established at the time
    • Structural basis of the interaction not solved
  4. 2004 High

    Connected LHX2 to direct target-gene regulation by demonstrating it binds the M71 odorant-receptor promoter and is required for terminal OSN differentiation and OR expression, establishing LHX2 as a direct activator of differentiation genes.

    Evidence yeast one-hybrid, EMSA, and knockout mouse with immunostaining

    PMID:15173589 PMID:15456728

    Open questions at the time
    • Whether binding is direct at all OR loci vs. indirect not resolved at the time
    • Cofactor requirements unaddressed
  5. 2008 High

    Defined LHX2 as a cell-autonomous cortical selector gene acting within an early progenitor critical period, and showed cooperative target activation with Pax6 at Six6, framing LHX2 as a combinatorial fate-specifying factor.

    Evidence genetic mosaics, timed Cre-lox inactivation, ChIP, and reporter co-transactivation

    PMID:18202285 PMID:19146846

    Open questions at the time
    • Chromatin-level mechanism of fate suppression not yet defined
    • Full partner complex unknown
  6. 2008 High

    Identified the SSBP3-Lhx2-Ldb1 trimeric DNA-binding complex and its assembly logic, showing SSBP3 stabilizes the factors and promotes promoter recruitment—the first reconstruction of LHX2's higher-order transcriptional machinery.

    Evidence EMSA/supershift, ChIP, and gain/loss-of-function in pituitary cells

    PMID:18565323

    Open questions at the time
    • Stoichiometry of the full tetrameric complex not resolved here
    • Generalizability beyond pituitary targets untested
  7. 2011 High

    Showed LHX2 controls progenitor-versus-differentiation balance by gating Notch (Hes1) and the neuron-to-glia switch, establishing it as a maintenance factor that suppresses premature differentiation and astrogliogenesis.

    Evidence conditional knockout, in utero electroporation, and Notch/Nfia epistasis

    PMID:21690374 PMID:23454273

    Open questions at the time
    • Direct vs. indirect regulation of Hes1 not fully resolved
    • Spatial restriction of the glial-switch role to hippocampus mechanistically unexplained
  8. 2013 High

    Defined LHX2's chromatin-remodeling mechanism by showing it recruits NuRD (LSD1/HDAC2/RBBP4) to repress fate genes and directly binds Pax6/Cer1 enhancers, linking LHX2 to active modulation of histone state at target loci.

    Evidence Co-IP with NuRD subunits, ChIP for binding and histone marks, ChIP-seq in HF-SCs, and gain/loss-of-function

    PMID:23804753 PMID:24012369 PMID:28053041

    Open questions at the time
    • How LHX2 selects activating versus repressive chromatin outcomes at different loci not resolved
    • Reciprocal validation of all NuRD subunit contacts limited
  9. 2013 Medium

    Established LHX2 as a non-degradative protein destabilizer in hematopoiesis: by competing LMO2 off LDB1 it triggers LMO2 ubiquitin-proteasome degradation, reducing Gata3 and blocking differentiation to expand HSC-like cells.

    Evidence inducible Lhx2 overexpression in ESC-derived HPCs, LMO2 stability western blots, and Gata3 knockdown

    PMID:23922318

    Open questions at the time
    • Mechanism shown in a single in vitro HPC system
    • In vivo contribution to physiological HSC maintenance not directly tested here
  10. 2014 High

    Extended the partner-sequestration mechanism to bone, showing LHX2 binds c-Fos to attenuate its DNA binding and NFATc1 transactivation, with conditional knockout producing osteoporosis—linking the in vitro mode to organismal phenotype.

    Evidence Co-IP, DNA-binding competition, conditional knockout, and bone histomorphometry

    PMID:24902903

    Open questions at the time
    • Structural basis of the c-Fos interaction unresolved
    • Whether the same sequestration applies to other AP-1 family members untested
  11. 2016 High

    Resolved LHX2 as a multilevel signaling-pathway regulator in the retina, directly controlling Notch ligands/effectors and FGF expression to govern Muller glia specification and lens fiber differentiation.

    Evidence temporally controlled conditional knockouts, direct-target analysis, and FGF/Hes5 genetic rescue

    PMID:26911688 PMID:27633990

    Open questions at the time
    • Direct binding at every implicated pathway gene not uniformly demonstrated
    • Quantitative contribution of each pathway to phenotype not separated
  12. 2019 High

    Revealed LHX2's most striking chromatin role: with LDB1 it orchestrates interchromosomal contacts among olfactory-receptor clusters from 18 chromosomes to build a multi-chromosomal super-enhancer driving singular OR transcription.

    Evidence in situ Hi-C on sorted OSNs, conditional knockout/knockdown, and Greek-island ChIP

    PMID:30626972

    Open questions at the time
    • How LHX2/LDB1 select which OR locus becomes active not resolved
    • Whether the same 3D mechanism operates outside the olfactory system unknown
  13. 2023 Medium

    Linked LHX2 to human disease by demonstrating that pathogenic missense variants act through loss of function—impairing DNA binding (nucleolar mislocalization), LDB1 interaction, or transactivation—causing a neurodevelopmental disorder, and defining an OTX2/LDB1/BAF module regulating RPE genes with an AMD-causal SNP.

    Evidence variant localization, cofactor-interaction and luciferase assays; ChIP-seq/ATAC-seq/proteomics with reporter validation in human RPE and mouse

    PMID:36649236 PMID:37057675

    Open questions at the time
    • Genotype-phenotype correlation across the variant spectrum incomplete
    • In vivo modeling of specific human variants not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LHX2 selects between activating and repressive transcriptional outcomes, and which cofactor composition (LDB1/SSBP3 vs. NuRD vs. BAF vs. OTX2) is recruited in each tissue context, remains unresolved.
  • No structural model of the tetrameric LHX2:LDB1 complex with accessory factors
  • Rules governing context-specific cofactor choice undefined
  • Mechanism distinguishing direct DNA-binding regulation from partner-sequestration in vivo unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-4839726 Chromatin organization 3
Partners
FOSLDB1LMO2MSX1OTX2PAX6SSBP3TCF4
Complex memberships
LHX2/OTX2/LDB1/BAF (SWI-SNF) moduleLHX2:LDB1 tetrameric complexNuRD complex (LSD1/HDAC2/RBBP4)SSBP3-Lhx2-Ldb1 trimeric complex

Evidence

Reading pass · 64 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 LH-2/LHX2 encodes a polypeptide containing two LIM domains (cysteine-rich zinc-finger motifs) and a homeodomain, identifying it as a LIM-homeodomain transcription factor with structural homology to Drosophila apterous. cDNA cloning and sequence analysis Proceedings of the National Academy of Sciences of the United States of America Medium 7678338
1997 Lhx2 is required cell-non-autonomously for definitive erythropoiesis, and cell-autonomously for eye (optic cup formation) and forebrain (neocortex, hippocampal anlage) development; loss-of-function causes severe anemia, anophthalmia, and cortical hypoplasia. Targeted knockout mouse, histology, embryo phenotypic analysis Development (Cambridge, England) High 9247336
1998 Lhx2 protein physically interacts with Msx1 homeoprotein through their homeodomain-containing regions (not LIM domains); this interaction occurs in the absence of DNA and is mutually exclusive with DNA binding by either protein. In vitro binding assay, pull-down from cellular extracts, electrophoretic mobility shift assay (EMSA) Differentiation; research in biological diversity High 9697309
1998 In vertebrates, Lhx2 regulates limb outgrowth (a function attributed to Drosophila apterous) while limb dorsoventral fate specification is performed by Lmx-1, indicating that functions of apterous are partitioned between two proteins in vertebrates. Gain-of-function misexpression in chick limb, loss-of-function analysis in mice Development (Cambridge, England) Medium 9735354
2001 Lhx2 is required to restrict the cortical hem to its medial position; in Lhx2-/- mice the cortical hem expands to cover almost the entire dorsal telencephalon, demonstrating that Lhx2 sets the boundary between cortical neuroepithelium and the cortical hem. Targeted knockout mouse, in situ hybridization, marker gene expression analysis Mechanisms of development High 11165475
2001 Lhx2 expression in the developing cortex is bimodally regulated by roof plate-derived BMP4 and BMP2 signals; roof plate ablation reduces cortical size and Lhx2 expression, placing Lhx2 downstream of a roof plate–BMP signaling axis in cortical patterning. Roof plate ablation, cortical explant BMP treatment, Lhx2 knockout analysis Neuron High 11719201
2001 Lhx2-immortalized multipotent hematopoietic progenitor cell (HPC) lines self-renew by a cell-non-autonomous mechanism dependent on functional Lhx2 expression; late-acting differentiation factors do not induce differentiation, whereas TGF-β1 potently inhibits their proliferation. Lhx2 expression in ES-cell-derived hematopoietic progenitors, in vitro growth factor analysis, stromal co-culture Experimental hematology Medium 11495708
2002 Lhx2 expression in adult bone marrow-derived hematopoietic progenitor/stem cells generates immortalized multipotent cell lines capable of long-term multilineage repopulation (erythroid, myeloid, lymphoid) upon transplantation into lethally irradiated and stem-cell-deficient mice. Retroviral Lhx2 transduction of adult bone marrow cells, transplantation into irradiated mice, lineage analysis Blood High 12010792
2004 Lhx2 binds the homeodomain binding site in the promoter region of the odorant receptor gene M71 (a class II OR), as demonstrated by yeast one-hybrid and EMSA; in Lhx2-deficient mice, mature olfactory sensory neurons (OMP+) are absent and OR gene expression is abolished, indicating Lhx2 is required for terminal OSN differentiation and OR gene expression. Yeast one-hybrid screen, EMSA, Lhx2 knockout mouse analysis, immunostaining Proceedings of the National Academy of Sciences of the United States of America High 15173589
2004 Lhx2 is required cell-autonomously in olfactory sensory neurons for their differentiation into regionally and individually specified subpopulations expressing distinct OR genes; in Lhx2-null mice, neurons acquire pan-neuronal traits but fail to diversify into OR-expressing subpopulations, with increased apoptosis and reduced late differentiation markers. Lhx2 knockout mouse, in situ hybridization, immunostaining, cell death assays Development (Cambridge, England) High 15456728
2004 Lhx2 is expressed in hepatic stellate cells (HSCs) derived from septum transversum mesenchyme; its inactivation in HSCs causes spontaneous liver fibrosis with deposition of ECM proteins and HSC activation. Transfection of Lhx2 cDNA into a human HSC line downregulates markers of activated HSCs, demonstrating Lhx2 negatively regulates HSC activation. Lhx2 knockout mouse, immunostaining, cDNA transfection into HSC line, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 15536133
2005 Lhx2 functions downstream of Six3 in zebrafish forebrain growth; head-specific overexpression of Lhx2 completely rescues the telencephalon size reduction in six3 double morphants, whereas Six3b overexpression cannot rescue lhx2 knockdown, establishing a Six3→Lhx2 epistatic relationship for forebrain cellular proliferation. Antisense morpholino knockdown, caged-mRNA photoactivation, rescue experiments in zebrafish Developmental biology High 16226737
2006 Lhx2 is positioned downstream of signals that specify hair follicle stem cells (including p63/NF-κB) but upstream of signals (Wnt/β-catenin, BMP, Shh) that drive terminal differentiation; gain- and loss-of-function in mice show Lhx2 maintains hair follicle progenitors in an undifferentiated, growth-competent state. Gain- and loss-of-function mouse genetics, transcriptional profiling of embryonic hair progenitors Science (New York, N.Y.) High 16809539
2007 Lhx2 has a differential effect on odorant receptor gene classes: loss of Lhx2 abolishes expression of all tested class II OR genes but spares most class I OR genes (except two ventrally expressed class I ORs), indicating Lhx2 is required for class II and a subset of class I OR gene expression. Lhx2 knockout mouse, in situ hybridization for class I and class II OR genes Molecular and cellular neurosciences High 17350283
2007 Lhx2 plays a dual role in lateral olfactory tract (LOT) formation: it is required in olfactory bulb (OB) mitral cells for LOT axon pioneering (but not mitral cell specification), and in the lateral telencephalon for providing a permissive substrate for LOT growth via proper positioning of 'lot cells' and normal Sema6A expression. Lhx2 knockout mouse, in vivo and in vitro explant LOT assays, cell tracking, in situ hybridization The Journal of neuroscience : the official journal of the Society for Neuroscience High 17329426
2007 Lhx2 activates transcription of the TSH beta-subunit gene by directly binding two distinct regions of the TSHβ promoter (-118 to -108 and -86 to -68) containing repeated (G/T)CAAT(T/A) motifs; Lhx2 expression is induced by TRH and cAMP in thyrotrope cells. EMSA, DNase I footprinting, reporter gene assay, deletion analysis, RT-PCR Endocrinology High 17446187
2006 Cofactor CLIM2 (Ldb1/NLI) interacts with porcine Lhx2 (identified by yeast two-hybrid) and acts as a corepressor of Lhx2 function on the alphaGSU gene in pituitary cells; CLIM2 itself represses alphaGSU transcription in LβT2 cells. Yeast two-hybrid, transfection reporter assay in LβT2 and CHO cells, RT-PCR Biochimica et biophysica acta Medium 17005264
2008 Lhx2 acts as a classic selector gene in the early cortical neuroepithelium, cell-autonomously specifying cortical identity and suppressing alternative fates (antihem laterally, cortical hem medially) within an early critical period restricted to when stem cells comprise the neuroepithelium. Mouse genetic mosaics, timed conditional inactivation using Cre-lox, marker analysis Science (New York, N.Y.) High 18202285
2008 Lhx2 and Pax6 synergistically transactivate the Six6 homeobox gene; both factors associate with Six6 chromatin in vivo (ChIP), cooperate for trans-activation of Six6 regulatory elements in vitro, and are both genetically required for Six6 expression in the optic vesicle. ChIP, reporter gene trans-activation assay, co-expression in retinal progenitor/stem cells, Lhx2-/- mouse analysis Developmental biology High 19146846
2008 An Lhx2-Ldb1-Ssbp3 trimeric complex binds a specific element in the Cga (glycoprotein hormone alpha subunit) promoter in pituitary cells; SSBP3 inhibits Lhx2 and Ldb1 turnover, stimulates assembly of this DNA-binding complex, promotes its recruitment to the Cga promoter, and enhances Cga transcription. EMSA, antibody supershift, ChIP, overexpression and knockdown in alphaT3-1 pituitary cells Biochemical and biophysical research communications High 18565323
2009 Lhx2 is required for optic cup formation by regulating BMP signaling in an autocrine manner in the optic neuroepithelium and paracrine manner in the lens ectoderm; Bmp4 and Bmp7 mRNAs are undetectable in Lhx2-/- optic vesicles, and Lhx2 genetic mosaics show cell-autonomous requirement for transcription factors Vsx2 and Mitf. Lhx2 conditional knockout, BMP treatment of Lhx2-/- explants, genetic mosaics, in situ hybridization Development (Cambridge, England) High 19906857
2009 Lhx2 is required for development of the posterior pituitary lobe; deletion causes persistent cell proliferation and failure of neuroectoderm evagination in the ventral diencephalon. Rathke's pouch and anterior/intermediate pituitary form but their shape is secondarily disrupted. Lhx2 knockout mouse, histology, BrdU labeling, marker gene expression Developmental biology Medium 19900438
2010 Lhx2 is cyclically expressed in hair follicle precursor cells (outer root sheath, matrix cells) during anagen, becomes undetectable in telogen, and reappears prior to anagen onset; conditional loss of Lhx2 impairs anagen progression and HF morphogenesis, while transgenic overexpression is sufficient to induce anagen. Transgenic mouse overexpression, conditional knockout, immunostaining, cyclic expression analysis PLoS genetics High 20386748
2011 Lhx2 is a necessary and sufficient regulator of the neuron-to-glia cell fate switch in the developing hippocampus: loss of Lhx2 causes premature astrogliogenesis at neurogenic stages; overexpression suppresses astrogliogenesis and can override the instructive astrogliogenic effect of Notch activation and Nfia-mediated GFAP promoter activation. This function is spatially restricted to the hippocampus. In utero electroporation, organotypic slice culture, Lhx2 overexpression and knockdown, Notch/Nfia interaction tests Proceedings of the National Academy of Sciences of the United States of America High 21690374
2011 Lhx2 directly transactivates Sox9 and Tcf4 (positive regulation) and negatively regulates Lgr5 in hair follicle stem cells, as demonstrated by ChIP-on-chip/ChIP-qPCR and reporter assay; these differential effects underlie distinct roles in wound re-epithelization versus hair follicle cycling. ChIP-on-chip, ChIP-qPCR, reporter assay, heterozygous Lhx2 knockout skin injury model, Lgr5 siRNA Development (Cambridge, England) High 22028024
2011 Lhx2 in zebrafish thalamus is required for proper neuronal differentiation; loss of Lhx2/Lhx9 causes upregulation of Wnt signaling and expansion of epithalamic territory into the thalamus, and alters expression of thalamic cell adhesion factor pcdh10b, disrupting compartment integrity. Zebrafish Lhx2/Lhx9 morpholino knockdown, Wnt reporter assays, in situ hybridization PLoS biology Medium 22180728
2012 miR-124a targets Lhx2 mRNA in vivo; Rncr3-/- mice (deficient in the dominant source of miR-124a) show increased Lhx2 protein and display CNS defects including axonal mis-sprouting of dentate gyrus granule cells and retinal cone cell death, which are rescued by LHX2 downregulation. Targeted disruption of Rncr3 (miR-124a source), in vivo validation of LHX2 as miR-124a target, phenotypic analysis Nature neuroscience High 21857657
2012 Selective deletion of Lhx2 from mature Müller glia induces reactive retinal gliosis in the absence of injury, demonstrating that Lhx2 actively maintains Müller glia in a non-reactive state; the resulting gliosis is hypertrophic but not proliferative, reduces neuroprotective factor secretion, and impairs photoreceptor function. Conditional knockout of Lhx2 in mature Müller glia, ERG, immunostaining, light-damage assay Proceedings of the National Academy of Sciences of the United States of America High 22393024
2012 Lhx2 in thalamic neurons directly regulates expression of axon guidance receptors Robo1 and Robo2, which are required for correct topographic sorting of thalamocortical axons; Robo1 overexpression restores normal axon guidance in Lhx2-overexpressing thalamic neurons. Conditional Lhx2 deletion in thalamus, Lhx2 overexpression in vivo, Robo1 rescue experiment, in situ hybridization The Journal of neuroscience : the official journal of the Society for Neuroscience High 22457488
2012 Lhx2-dependent specification of olfactory sensory neurons is required cell-autonomously for OSN axonal innervation of the olfactory bulb, and non-cell-autonomously for olfactory bulb size, vomeronasal nerve formation, and GnRH neuron migration to the hypothalamus. Conditional Lhx2 inactivation selectively in OSNs, postnatal and prenatal phenotypic analysis FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 22581782
2013 LHX2 interacts with the NuRD chromatin remodeling complex subunits LSD1, HDAC2, and RBBP4; it binds distal regulatory elements of Fezf2 and Sox11 in cortical progenitors. Loss of LHX2 increases active histone marks at Fezf2 and Sox11 loci, and LHX2 levels bidirectionally regulate the number of deep-layer Fezf2/CTIP2-expressing neurons. Co-IP of LHX2 with NuRD subunits, ChIP for LHX2 and histone marks at target loci, conditional knockout and overexpression, cortical layer analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 28053041
2013 LHX2 in cortical progenitors directly binds PAX6 active enhancers to promote PAX6 expression, and promotes expression of the BMP/WNT antagonist Cerberus 1 (CER1) to attenuate non-neural differentiation, thereby regulating human neural differentiation at two levels. ChIP in hESC-derived neural progenitors, conditional LHX2 overexpression and knockdown in hESCs, reporter assays Nucleic acids research High 23804753
2013 LHX2 directly transactivates genes orchestrating cytoskeletal dynamics and adhesion in hair follicle stem cells (HF-SCs), as shown by genome-wide chromatin and transcriptional profiling; conditional ablation of LHX2 causes gross cellular disorganization, loss of HF-SC polarity and quiescence, failure of hair anchoring, and progressive transformation of the niche into sebaceous gland. Genome-wide ChIP-seq, transcriptional profiling, conditional LHX2 knockout in HF-SCs, histology Cell stem cell High 24012369
2013 Lhx2 is continuously required throughout multiple stages of optic development to maintain optic identity by suppressing thalamic eminence/anterodorsal hypothalamic fate; timed conditional knockouts show that the longer Lhx2 function is maintained, the further optic morphogenesis progresses. Timed conditional knockout strategy in mice at multiple stages, molecular marker analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 23595746
2013 Lhx2 balances retinal progenitor cell (RPC) maintenance with neurogenesis; conditional inactivation reduces the progenitor pool and increases neurogenesis, with fate biased toward cell types appropriate to the time of inactivation (RGCs early, rods late); Lhx2 facilitates the transition of RPCs to a new competence state. Temporal series of conditional Lhx2 inactivations in RPCs using Pax6-αCre and Hes1-CreERT2 drivers, cell fate analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 23884928
2013 Lhx2 is required in the cortex for somatosensory barrel formation; conditional loss causes absence of barrels and loss of whisker-evoked responses, which is linked to Lhx2-dependent expression of Pax6, EphrinA5, and NMDAR1 in cortical neurons. Conditional Lhx2 knockout in dorsal telencephalon, electrophysiology, in situ hybridization, molecular marker analysis Proceedings of the National Academy of Sciences of the United States of America High 24262147
2013 Lhx2 regulates formation of the forebrain hem system (cortical hem, septum, thalamic eminence): loss of Lhx2 causes expansion of all three structures and dramatic increase in Cajal-Retzius cells, demonstrating Lhx2 delimits all components of the forebrain hem system. Conditional Lhx2 knockout at different stages, in situ hybridization for hem/septum/TE markers, cell counting Cerebral cortex (New York, N.Y. : 1991) High 23307637
2014 Lhx2 conditional inactivation in cortical radial glia (via Emx1-Cre or Nestin-Cre) causes agenesis of the corpus callosum due to failure of glial wedge (GW) formation; GW progenitors expressing Lhx2 exit the cell cycle prematurely, and the ACC phenotype is not autonomous to callosal projection neurons. Conditional Lhx2 knockout with multiple Cre drivers, EdU-Ki67 double labeling, axon tracing, GW marker analysis Cerebral cortex (New York, N.Y. : 1991) High 24781987
2014 Lhx2 directly binds chromatin in tanycytes and directly regulates Rax expression, which is essential for tanycyte-specific gene activation; embryonic Lhx2 deletion in posteroventral hypothalamic neuroepithelium disrupts tanycyte specification and causes ectopic expression of cuboid ependymal cell markers, while postnatal deletion only causes loss of tanycyte-specific gene expression. Conditional Lhx2 knockout (embryonic and postnatal), ChIP, electron microscopy, immunostaining The Journal of neuroscience : the official journal of the Society for Neuroscience High 25505333
2014 Lhx2 inhibits osteoclast differentiation by interacting with c-Fos to attenuate c-Fos DNA-binding activity, thereby inhibiting NFATc1 transactivation; conditional Lhx2 knockout mice display osteoporotic bone phenotype with increased osteoclast formation. Lhx2 overexpression in BMMs, Co-IP of Lhx2 with c-Fos, DNA-binding assay, conditional knockout mouse, bone histomorphometry Cell death and differentiation High 24902903
2014 Lhx2 directly activates transcription of Msx1 and Msx2 by binding to two consensus sites each in their regulatory regions (verified by EMSA and ChIP); Lhx2 overexpression inhibits skeletal muscle differentiation in C2C12 cells and primary myoblasts, and Lhx2 knockdown in developing limb buds reduces Msx1/Msx2 mRNA levels. Luciferase reporter assay with site mutation, EMSA, ChIP, Lhx2 overexpression in C2C12, siRNA knockdown in limb buds Experimental cell research High 25460335
2014 Lhx2 is a direct NF-κB target gene in hair follicle placodes; Lhx2 loss replicates subset of NF-κB-deficient HF phenotypes; LHX2 operates upstream of TGFβ2 in a NF-κB→LHX2→TGFβ2 signaling axis required for primary HF morphogenesis, as exogenous TGFβ2 rescues HF defects in Lhx2 knockout skin explants. NF-κB-reporter placode isolation, transcriptional profiling, conditional knockout, TGFβ2 rescue in skin explants, ChIP/reporter for NF-κB binding to Lhx2 Development (Cambridge, England) High 26952977
2015 Lhx2 maintains cortical progenitor proliferation by enabling the Wnt/β-catenin pathway; in the absence of Lhx2, the Wnt/β-catenin pathway fails to maintain progenitor proliferation, causing precocious radial glia differentiation and a temporal shift (earlier onset) of cortical neurogenesis. Nestin-Cre conditional Lhx2 knockout, β-catenin pathway analysis, mathematical modeling of cortical surface/thickness Proceedings of the National Academy of Sciences of the United States of America High 26371318
2016 Lhx2 is essential for retinal Müller glia (MG) development at all stages; it directly regulates expression of Notch pathway genes (Notch1, Dll1, Dll3) and gliogenic transcription factors (Hes1, Hes5, Sox8, Rax); conditional Lhx2 knockout rapidly downregulates Notch signaling and blocks MG specification. Temporally controlled conditional Lhx2 knockout in retinal progenitors, ChIP or direct target analysis, Hes5 misexpression rescue experiment The Journal of neuroscience : the official journal of the Society for Neuroscience High 26911688
2016 Lhx2 is required in neuroretina for expression of multiple FGFs; loss of Lhx2 in neuroretina reduces FGF expression and causes arrest of lens fiber development; genetic restoration of FGF expression in Lhx2-deficient neuroretina partially rescues lens cell proliferation, survival, and fiber differentiation. Chx10-Cre; Lhx2lox/lox conditional knockout, FGF genetic rescue experiment in Lhx2-deficient neuroretina Development (Cambridge, England) High 27633990
2016 Lhx2 determines odorant receptor expression frequency in mature olfactory sensory neurons by directly driving OR gene expression; conditional deletion of Lhx2 in immature or mature OSNs reduces expression frequencies of nearly all ORs and all trace amine-associated receptors, independent of when deletion is initiated. Conditional Lhx2 deletion in OSNs at different stages, quantitative OR expression frequency analysis eNeuro High 27822500
2017 Lhx2 in postmitotic layer 4 cortical neurons is required for barrel formation; when deleted post-mitotically, L4 neurons fail to form cellular barrels and develop polarized dendrites, TCAs fail to arborize, and Btbd3 (an activity-regulated gene controlling dendritic development) is identified as a direct downstream target of Lhx2. Postmitotic conditional Lhx2 knockout, ChIP/reporter identifying Btbd3 as direct target, thalamocortical axon tracing, electrophysiology Cell reports High 28122236
2018 Lhx2 interacts with Ldb1 in a conserved tetrameric LHX:LDB complex; this interaction is required for hippocampal cell fate and regional identity. Expression of a chimeric Lhx2-HD/Ldb1-DD construct cell-autonomously rescues hippocampal deficits (field-specific molecular identity, neuron-glia switch) in Ldb1 mutant mice, demonstrating functional conservation of the LHX:LDB complex from Drosophila to mammals. Electroporation of chimeric Lhx2-Ldb1 construct into Ldb1 mutant mouse cortex, marker analysis, cell fate assessment Development (Cambridge, England) High 32994168
2018 Lhx2 mediates the FGF-to-SHH regulatory feedback loop during limb development, acting as a competency factor that maintains distal posterior SHH expression; LHX2 is an intermediate in FGF-mediated regulation of SHH. FGF bead implantation in limb bud, transcriptome comparative analysis, identification of LHX2 as intermediate Journal of developmental biology Medium 29914077
2018 Dmrt5 and Lhx2 are reciprocally regulated in the developing hippocampus: each can compensate for loss of the other in controlling the neuron-glia cell fate switch; Lhx2 binds a conserved putative enhancer of Dmrt5, and they have opposing regulatory control on Pax6 and Neurog2. In utero electroporation of Dmrt5 overexpression and knockdown, rescue of Lhx2 loss, ChIP-qPCR of Lhx2 at Dmrt5 enhancer The Journal of neuroscience : the official journal of the Society for Neuroscience High 29025924
2018 Lhx2 overexpression/co-activity with Ldb1 triggers cell cycle exit and inhibits Notch signaling and retinal gliogenesis while inducing wide-field amacrine cell (wfAC) formation; Lhx2-dependent neurogenesis and wfAC formation requires Ascl1 and Neurog2, and Lhx2 is necessary for their expression. The ratio of LHX2-LDB1 complex decreases at onset of gliogenesis; Rnf12, a negative regulator of LDB1, is necessary for initiating retinal gliogenesis. Lhx2/Ldb1 overexpression electroporation, Rnf12 knockout, quantitative protein complex analysis, cell fate analysis Development (Cambridge, England) High 29650591
2018 FOXG1 regulates Lhx2 expression in the cortical primordium; Foxg1 and Lhx2 form a genetic hierarchy controlling cortical hem specification and positioning, where loss of either gene expands the hem and loss of Foxg1 is buffered by residual Lhx2 activity. Conditional knockouts of Foxg1 and Lhx2 singly and in combination, epistasis analysis by double knockout, marker expression analysis Development (Cambridge, England) High 29229772
2019 LHX2 and adaptor protein LDB1 regulate olfactory receptor gene compartment assembly, Greek island hub formation, and OR transcription; Hi-C in sorted olfactory sensory neurons shows LHX2/LDB1 orchestrate specific interchromosomal contacts between OR gene clusters from 18 chromosomes that increase with differentiation, forming a multi-chromosomal super-enhancer at the active OR gene. In situ Hi-C on FACS-sorted OSNs, conditional knockout/knockdown of LHX2 and LDB1, ChIP for Greek island enhancers Nature High 30626972
2011 Lhx2 is required for Hes1 expression in cortical progenitors; loss of Lhx2 causes premature neuronal differentiation and reduced Hes1 levels, placing Lhx2 upstream of Hes1 in the Notch signaling pathway that maintains progenitor proliferation in the neocortex. Conditional Lhx2 knockout in cortical progenitors, Hes1 immunostaining and RT-PCR, progenitor pool quantification Molecular and cellular neurosciences Medium 23454273
2013 In hematopoietic progenitor cells, Lhx2 destabilizes Lmo2 protein by displacing it from the Lmo2-Ldb1 complex (since LIM-HD factors compete with LMO for Ldb1 binding), leading to ubiquitin-proteasome-mediated Lmo2 degradation; this reduces Gata3 expression and inhibits mature hematopoietic cell differentiation, promoting HSC-like cell accumulation. Lhx2 inducible overexpression in ESC-derived HPCs on OP9 stromal cells, western blot for Lmo2 stability, Gata3 knockdown Stem cells (Dayton, Ohio) Medium 23922318
2017 Lhx2 overexpression in human T-ALL cells suppresses LMO2 protein levels (through displacement from LDB1 complex), represses HHEX, ERG, HES1, and MYC expression, and induces G0 arrest followed by apoptosis; both C-terminal LIM domain and homeodomain of Lhx2 are required for growth-suppressive activity; Lmo2 overexpression partially rescues Lhx2-mediated growth inhibition. Retroviral Lhx2 overexpression in 5 T-ALL cell lines, LMO2 western blot, Lmo2 rescue overexpression, cell cycle analysis, domain mutant analysis Biochemical and biophysical research communications Medium 29278703
2011 Lhx2 cloned as transcription factor for porcine FSHβ gene; Lhx2 binds the AATTAAT consensus sequence at multiple sites in the Fd2 region of the FSHβ promoter as demonstrated by yeast one-hybrid, SELEX, and DNase I footprinting; reporter assay confirmed Lhx2-responsive regions. Yeast one-hybrid cloning, SELEX (AATTAAT consensus), DNase I footprinting, reporter assay The Journal of reproduction and development Medium 22134063
2022 Lhx2 in retinal progenitors acts as a multilevel regulator of Sonic Hedgehog (Shh) signaling: it cell-autonomously controls expression of Shh co-receptors Cdon and Gas1 (candidate direct targets) and other pathway components required for efficient Shh activation; Lhx2 also provides the context linking Shh pathway activation to downstream targets during early retinal neurogenesis. Conditional Lhx2 knockout in retinal progenitors, ChIP for Cdon/Gas1 as direct targets, genetic epistasis with Shh pathway components eLife High 36459481
2022 LHX2 transcriptionally activates FGF1 expression by binding to the FGF1 promoter; the resulting FGF1 activates STAT3, ERK1/2, and AKT signaling in an autocrine/paracrine manner, promoting NPC cell growth and metastasis; siRNA against FGF1 or FGFR inhibitor blocks LHX2-induced effects. ChIP assay, luciferase reporter assay, siRNA knockdown, FGFR inhibitor treatment, xenograft and lung metastasis models British journal of cancer Medium 35864158
2022 LHX2 in esophageal squamous cell carcinoma binds the SERPINE2 promoter and transcriptionally upregulates SERPINE2 expression; LHX2 knockdown inhibits ESCC proliferation, migration, and invasion, while overexpression has opposite effects. ChIP, luciferase reporter, loss- and gain-of-function in ESCC cells, xenograft Genes Medium 36011368
2023 LHX2 missense variants in the HOX DNA-binding domain cause nucleolar accumulation of the protein; variants in the LIM protein-protein interaction domain impair interaction with co-factor LDB1; four missense variants impair transcriptional activation in luciferase assays, indicating loss-of-function mechanism for pathogenic LHX2 variants causing neurodevelopmental disorder. Cellular localization studies, co-factor interaction assays, luciferase transcriptional activation assay for missense variants Genetics in medicine : official journal of the American College of Medical Genetics Medium 37057675
2023 LHX2 and OTX2 function together in a transcriptional module containing LDB1 and SWI/SNF (BAF) complex to regulate the retinal pigmented epithelium (RPE) transcriptome; their combined cistrome at RPE regulatory elements modulates TRPM1 expression, and a causal AMD-associated SNP alters LHX2 transcriptional activity at the TRPM1 promoter. ChIP-seq (LHX2, OTX2, LDB1, BAF), ATAC-seq, RNA-seq, proteomics, luciferase reporter for causal SNP, stem cell-derived human RPE and mouse in vivo studies PLoS biology High 36649236
2024 Lhx2 in hepatic stellate cells (HSCs) suppresses TGF-β signaling by upregulating SMAD6; it also upregulates the pro-regenerative factor HGF, thereby simultaneously promoting hepatocyte proliferation and suppressing fibrosis; Lhx2 knockdown impairs liver recovery after acute injury. RNA-seq of primary mouse HSCs, HSC-specific Lhx2 overexpression and knockdown in CCl4 mouse models, scRNA-seq, mechanistic pathway analysis Hepatology (Baltimore, Md.) Medium 39693275
2014 Lhx2 forms a complex with TCF4 and β-catenin in pancreatic ductal adenocarcinoma cells (Lhx2/TCF4/β-catenin complex) that transactivates downstream target genes; Lhx2 mutations disrupting the Lhx2-β-catenin interaction partially prevent its function in tumor cells. Co-immunoprecipitation, β-catenin reporter assay, Lhx2 domain mutants Molecular biology reports Low 25324171

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development. Development (Cambridge, England) 409 9247336
2006 Lhx2 maintains stem cell character in hair follicles. Science (New York, N.Y.) 282 16809539
2019 LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice. Nature 261 30626972
2008 Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate. Science (New York, N.Y.) 259 18202285
2011 miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression. Nature neuroscience 241 21857657
2001 Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway. Neuron 228 11719201
1993 LH-2: a LIM/homeodomain gene expressed in developing lymphocytes and neural cells. Proceedings of the National Academy of Sciences of the United States of America 183 7678338
2001 LIM-homeodomain gene Lhx2 regulates the formation of the cortical hem. Mechanisms of development 148 11165475
2004 The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 127 15173589
2011 Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury. Development (Cambridge, England) 106 22028024
2011 Lhx2 and Lhx9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling. PLoS biology 98 22180728
2014 Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps to identify comparable subdivisions in the developing hippocampal formation of mouse and chicken. Frontiers in neuroanatomy 90 25071464
2005 Lhx2 mediates the activity of Six3 in zebrafish forebrain growth. Developmental biology 88 16226737
2013 Architectural niche organization by LHX2 is linked to hair follicle stem cell function. Cell stem cell 84 24012369
2008 The LIM homeobox transcription factor Lhx2 is required to specify the retina field and synergistically cooperates with Pax6 for Six6 trans-activation. Developmental biology 84 19146846
2009 Lhx2 links the intrinsic and extrinsic factors that control optic cup formation. Development (Cambridge, England) 83 19906857
2011 Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus. Proceedings of the National Academy of Sciences of the United States of America 82 21690374
2016 Lhx2 Is an Essential Factor for Retinal Gliogenesis and Notch Signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 26911688
2004 Lhx2-/- mice develop liver fibrosis. Proceedings of the National Academy of Sciences of the United States of America 78 15536133
2004 The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity. Development (Cambridge, England) 76 15456728
2012 Injury-independent induction of reactive gliosis in retina by loss of function of the LIM homeodomain transcription factor Lhx2. Proceedings of the National Academy of Sciences of the United States of America 74 22393024
2019 MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2. Journal of experimental & clinical cancer research : CR 72 30791932
2013 LHX2 is necessary for the maintenance of optic identity and for the progression of optic morphogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 66 23595746
2013 LHX2 regulates the neural differentiation of human embryonic stem cells via transcriptional modulation of PAX6 and CER1. Nucleic acids research 65 23804753
2017 LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 28053041
2013 Lhx2 balances progenitor maintenance with neurogenic output and promotes competence state progression in the developing retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 61 23884928
2013 Lhx2 regulates the development of the forebrain hem system. Cerebral cortex (New York, N.Y. : 1991) 59 23307637
2012 The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 22457488
2007 Differential impact of Lhx2 deficiency on expression of class I and class II odorant receptor genes in mouse. Molecular and cellular neurosciences 57 17350283
1998 Lhx2, a vertebrate homologue of apterous, regulates vertebrate limb outgrowth. Development (Cambridge, England) 56 9735354
2018 Lhx2, an evolutionarily conserved, multifunctional regulator of forebrain development. Brain research 55 29522720
2002 Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo. Blood 54 12010792
2014 The LIM homeodomain factor Lhx2 is required for hypothalamic tanycyte specification and differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 25505333
2015 Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 52 26371318
2013 Role for Lhx2 in corticogenesis through regulation of progenitor differentiation. Molecular and cellular neurosciences 50 23454273
2016 Lhx2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth. Development (Cambridge, England) 47 26952977
2010 Cyclic expression of lhx2 regulates hair formation. PLoS genetics 47 20386748
2009 A role of the LIM-homeobox gene Lhx2 in the regulation of pituitary development. Developmental biology 46 19900438
2011 In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2. Blood 45 21343610
2013 Lhx2 regulates a cortex-specific mechanism for barrel formation. Proceedings of the National Academy of Sciences of the United States of America 44 24262147
2004 Lhx2 is expressed in the septum transversum mesenchyme that becomes an integral part of the liver and the formation of these cells is independent of functional Lhx2. Gene expression patterns : GEP 44 15261829
2015 miR-1238 inhibits cell proliferation by targeting LHX2 in non-small cell lung cancer. Oncotarget 39 26189214
2015 Mapping the expression of epithelial hair follicle stem cell-related transcription factors LHX2 and SOX9 in the human hair follicle. Experimental dermatology 35 25808706
2011 Lhx2 is required for patterning and expansion of a distinct progenitor cell population committed to eye development. PloS one 35 21886788
1998 Protein complex formation between Msx1 and Lhx2 homeoproteins is incompatible with DNA binding activity. Differentiation; research in biological diversity 35 9697309
2018 Hierarchical genetic interactions between FOXG1 and LHX2 regulate the formation of the cortical hem in the developing telencephalon. Development (Cambridge, England) 33 29229772
2017 Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit. Cell reports 32 28122236
2016 Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis. Scientific reports 32 27605455
2007 Early thalamocortical tract guidance and topographic sorting of thalamic projections requires LIM-homeodomain gene Lhx2. Developmental biology 29 17493606
2007 Dual role for LIM-homeodomain gene Lhx2 in the formation of the lateral olfactory tract. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 17329426
2012 Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 22581782
2017 Inhibition of LHX2 by miR-124 suppresses cellular migration and invasion in non-small cell lung cancer. Oncology letters 25 28927097
2014 Oncogenicity of LHX2 in pancreatic ductal adenocarcinoma. Molecular biology reports 25 25324171
2006 Expression of Xenopus laevis Lhx2 during eye development and evidence for divergent expression among vertebrates. Developmental dynamics : an official publication of the American Association of Anatomists 25 16470628
2019 Use of Mass Spectrometry to Profile Peptides in Whey Protein Isolate Medium Fermented by Lactobacillus helveticus LH-2 and Lactobacillus acidophilus La-5. Frontiers in nutrition 24 31681785
2018 Ldb1- and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in the retina. Development (Cambridge, England) 24 29650591
2014 Agenesis of the Corpus Callosum Due to Defective Glial Wedge Formation in Lhx2 Mutant Mice. Cerebral cortex (New York, N.Y. : 1991) 24 24781987
2008 Lhx2 expression promotes self-renewal of a distinct multipotential hematopoietic progenitor cell in embryonic stem cell-derived embryoid bodies. PloS one 24 18431502
2019 miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2. Journal of cellular biochemistry 23 31017720
2014 Lhx2 regulates bone remodeling in mice by modulating RANKL signaling in osteoclasts. Cell death and differentiation 23 24902903
2019 LHX2 promotes malignancy and inhibits autophagy via mTOR in osteosarcoma and is negatively regulated by miR-129-5p. Aging 22 31724536
2017 Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the Neuron-Glia Cell-Fate Switch in the Developing Hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 29025924
2016 Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons. eNeuro 20 27822500
2016 Control of lens development by Lhx2-regulated neuroretinal FGFs. Development (Cambridge, England) 19 27633990
2007 Activation of the thyroid-stimulating hormone beta-subunit gene by LIM homeodomain transcription factor Lhx2. Endocrinology 19 17446187
2001 Multipotent hematopoietic progenitor cells immortalized by Lhx2 self-renew by a cell nonautonomous mechanism. Experimental hematology 18 11495708
2010 Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort. American journal of medical genetics. Part A 17 20949537
2007 Search for the sex-determining switch in monotremes: mapping WT1, SF1, LHX1, LHX2, FGF9, WNT4, RSPO1 and GATA4 in platypus. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 17 17717721
2020 Accelerated evolution of an Lhx2 enhancer shapes mammalian social hierarchies. Cell research 16 32238901
2022 LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis. British journal of cancer 15 35864158
2018 LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development. Journal of developmental biology 15 29914077
2013 Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic progenitor cells derived from mouse embryonic stem cells. Stem cells (Dayton, Ohio) 15 23922318
2006 Lhx2--decisive role in epithelial stem cell maintenance, or just the "tip of the iceberg"? BioEssays : news and reviews in molecular, cellular and developmental biology 15 17117482
2000 Conserved overlapping and reciprocal expression of msh/Msx1 and apterous/Lhx2 in Drosophila and mice. Mechanisms of development 15 11091089
2014 Cyclic expression of Lhx2 is involved in secondary hair follicle development in cashmere goat. Gene expression patterns : GEP 14 25128627
2008 Single-stranded DNA-binding proteins regulate the abundance and function of the LIM-homeodomain transcription factor LHX2 in pituitary cells. Biochemical and biophysical research communications 14 18565323
2020 An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity. Development (Cambridge, England) 12 32994168
2009 Developmental expression of apterous/Lhx2/9 in the sepiolid squid Euprymna scolopes supports an ancestral role in neural development. Evolution & development 12 19601969
2006 Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha subunit gene. Biochimica et biophysica acta 12 17005264
2003 Lhx2 expression in hematopoietic progenitor/stem cells in vivo causes a chronic myeloproliferative disorder and altered globin expression. Haematologica 12 14687986
2022 LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2. Genes 11 36011368
2019 Cux2 expression regulated by Lhx2 in the upper layer neurons of the developing cortex. Biochemical and biophysical research communications 11 31708105
2015 Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1. The Journal of investigative dermatology 11 26176759
2011 Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus. PloS one 11 21629789
2010 Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia. Molecular vision 11 21203406
2024 Lhx2 specifically expressed in HSCs promotes liver regeneration and inhibits liver fibrosis. Hepatology (Baltimore, Md.) 10 39693275
2023 LHX2 haploinsufficiency causes a variable neurodevelopmental disorder. Genetics in medicine : official journal of the American College of Medical Genetics 10 37057675
2017 Overexpression of Lhx2 suppresses proliferation of human T cell acute lymphoblastic leukemia-derived cells, partly by reducing LMO2 protein levels. Biochemical and biophysical research communications 10 29278703
2023 The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration. PLoS biology 9 36649236
2022 Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary. Experimental cell research 9 35337816
2022 Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis. eLife 9 36459481
2015 OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo. Stem cell research 8 26339946
2014 LIM homeobox transcription factor Lhx2 inhibits skeletal muscle differentiation in part via transcriptional activation of Msx1 and Msx2. Experimental cell research 8 25460335
2012 Screening of LHX2 in patients presenting growth retardation with posterior pituitary and ocular abnormalities. European journal of endocrinology 8 22535646
2024 PRDM16 co-operates with LHX2 to shape the human brain. Oxford open neuroscience 7 38595939
2020 Lhx2/9 and Etv1 Transcription Factors have Complementary roles in Regulating the Expression of Guidance Genes slit1 and sema3a. Neuroscience 7 32200077
2014 Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells. Experimental cell research 7 24995995
2011 Molecular cloning of LIM homeodomain transcription factor Lhx2 as a transcription factor of porcine follicle-stimulating hormone beta subunit (FSHβ) gene. The Journal of reproduction and development 7 22134063
2004 Cloning and analysis of axolotl ISL2 and LHX2 LIM-homeodomain transcription factors. Genesis (New York, N.Y. : 2000) 7 15048808
2021 The combination of hair follicle-specific marker LHX2 and co-expressed marker can distinguish between sweat gland placodes and hair placodes in rat. Journal of molecular histology 6 34581932

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