Affinage

EMX2

Homeobox protein EMX2 · UniProt Q04743

Length
252 aa
Mass
28.3 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EMX2 is a homeodomain transcription factor that operates as a concentration-dependent patterning factor in multiple organ systems, specifying regional identity in the developing neocortex, establishing hair cell polarity in the inner ear, and regulating morphogenesis in the urogenital system. In the neocortex, EMX2 is expressed in a caudomedial-to-rostrolateral gradient where it cooperates with PAX6 in opposing gradients to specify cortical area identity; EMX2 represses FGF8 signaling, directly represses Wnt1 and Sox2 enhancers (competing with the POU factor Brn2), forms a heterodimer with Pbx1 to activate targets such as Alx1 and teneurin-1, and cooperates with DMRT3/DMRT5 to repress Gsx2 at the pallium–subpallium boundary, while also controlling the balance of symmetric versus asymmetric divisions in cortical progenitors (PMID:10764649, PMID:12872126, PMID:12668639, PMID:22495934, PMID:20627960, PMID:30143575, PMID:11922140). In the inner ear, EMX2 acts as a cell-autonomous polarity determinant expressed on one side of the line of polarity reversal, where it transcriptionally represses Stk32a and thereby permits GPR156 polarization and Gαi-mediated 180° reversal of stereociliary bundle orientation; this mechanism is established in the prosensory domain before hair cell specification and is conserved in mouse and zebrafish (PMID:28266911, PMID:34001891, PMID:37144879, PMID:38682291). In the urogenital system, EMX2 is required cell-autonomously for ureteric bud branching morphogenesis and is itself directly repressed by HOXA10 binding its promoter, while also regulating endometrial proliferation and male gonocyte differentiation via FGF9/NODAL signaling (PMID:9165114, PMID:12482956, PMID:27002001).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Establishing EMX2 as essential for kidney and brain development resolved its requirement in ureteric bud branching and dentate gyrus/hippocampus formation, demonstrating that this homeodomain factor has critical roles outside the cerebral cortex.

    Evidence Emx2 knockout mice with histological, molecular marker, and explant co-culture analyses

    PMID:9006071 PMID:9012509 PMID:9165114

    Open questions at the time
    • Downstream targets mediating ureteric bud branching unknown
    • Mechanism of dentate gyrus specification by EMX2 not defined
  2. 2000 High

    Demonstrating that EMX2 and PAX6 act in opposing gradients to specify cortical area identity established the counter-gradient model of neocortical arealization, answering how intrinsic transcription factors encode positional information across the cortical sheet.

    Evidence Reciprocal Emx2 and Pax6 knockout mice with area-specific marker and thalamocortical connection analysis

    PMID:10764649 PMID:10862700

    Open questions at the time
    • Direct transcriptional targets of EMX2 in area specification not identified
    • How gradient concentrations are translated into sharp areal boundaries unknown
  3. 2002 High

    Showing that EMX2 controls symmetric versus asymmetric division mode in cortical and adult neural stem cells revealed a mechanistic link between a patterning transcription factor and the fundamental decision governing stem cell self-renewal.

    Evidence Retroviral Emx2 transduction and Emx2 KO with clonal analysis in embryonic and adult neural stem cells

    PMID:11922140 PMID:11923200

    Open questions at the time
    • Cell cycle targets mediating division mode switch not identified
    • Whether division control is separable from area specification unclear
  4. 2002 High

    Identifying that Wnt/BMP signaling directly activates Emx2 transcription via Tcf/Smad sites in its enhancer, and that HOXA10 directly represses EMX2 via a defined promoter element, established EMX2 as a signal-responsive node integrating upstream morphogen and Hox inputs.

    Evidence Transgenic enhancer-reporter mutagenesis (Tcf/Smad sites); EMSA, DNase I footprinting, and site-directed mutagenesis of HOXA10 binding site in EMX2 promoter

    PMID:12070081 PMID:12482956

    Open questions at the time
    • Whether Wnt/BMP regulation of Emx2 is direct in all tissues or cortex-specific unknown
    • Chromatin context of HOXA10 repression not characterized
  5. 2003 High

    Demonstrating that EMX2 patterns cortical areas by regulating FGF8 levels — and that sequestering FGF8 rescues Emx2 mutant phenotypes — established a key epistatic relationship placing EMX2 upstream of a secreted morphogen in area specification.

    Evidence In vivo electroporation, Emx2 KO and overexpression with Fgf8 quantification, and rescue with truncated FGF receptor

    PMID:12872126

    Open questions at the time
    • Whether EMX2 directly represses Fgf8 transcription or acts indirectly not resolved
    • Contribution of other signaling molecules in EMX2-mediated patterning not addressed
  6. 2003 Medium

    Identifying EMX2 as a direct repressor of Wnt1 via a specific enhancer element, with deletion phenocopying Emx2 loss, established that EMX2 maintains cortical integrity by preventing ectopic Wnt1 expression.

    Evidence Transgenic mice with deleted EMX2 binding site in Wnt1 enhancer; phenotypic comparison with Emx2 KO

    PMID:12668639

    Open questions at the time
    • Direct binding of EMX2 to the Wnt1 enhancer not confirmed by ChIP
    • Whether other homeodomain factors can compensate at this site unknown
  7. 2004 High

    Showing that EMX2 protein localizes to olfactory neuron axons and physically interacts with eIF4E revealed an unexpected non-nuclear function, raising the possibility of EMX2 involvement in local translational control.

    Evidence Subcellular fractionation, co-immunoprecipitation, pull-down, and chemical lesion experiments in olfactory epithelium

    PMID:15247416

    Open questions at the time
    • Functional consequence of EMX2-eIF4E interaction on translation not demonstrated
    • Whether axonal EMX2 has transcription-independent targets unknown
    • Generalizability beyond olfactory neurons untested
  8. 2010 High

    Identifying EMX2 as forming a heterodimer with Pbx1 that cooperatively activates Alx1 transcription, and showing EMX2 directly represses Sox2 enhancers by competing with Brn2, defined the dual activator/repressor mechanism by which EMX2 controls specific target genes.

    Evidence Heterodimer binding assay, in vivo ChIP at Alx1 element, EMSA at Sox2 enhancers, genetic rescue in Sox2 hypomorphs

    PMID:20627960 PMID:22495934

    Open questions at the time
    • Genome-wide identification of EMX2-Pbx1 versus EMX2-alone target genes not performed
    • Whether Brn2 competition operates at all EMX2-repressed loci unknown
  9. 2017 High

    Discovering that EMX2 expression on one side of the line of polarity reversal is necessary and sufficient for 180° hair bundle reversal established EMX2 as a binary cell-autonomous polarity determinant in the inner ear, a fundamentally different role from its graded cortical function.

    Evidence Emx2 KO and gain-of-function in mouse vestibular organs and zebrafish neuromasts with hair bundle orientation analysis

    PMID:28266911

    Open questions at the time
    • Downstream effectors mediating the polarity reversal not yet identified
    • How EMX2 expression boundary is established in the maculae unknown
  10. 2018 High

    Demonstrating that EMX2 cooperates with DMRT3/DMRT5 to directly repress the Gsx2 enhancer at the pallium–subpallium boundary defined a cooperative transcription factor complex maintaining cortical identity against ventral telencephalic fate.

    Evidence Single and double KO mice; chromatin binding assay at Gsx2 enhancer; Dmrt5 overexpression

    PMID:30143575

    Open questions at the time
    • Stoichiometry and physical interactions among EMX2, DMRT3, and DMRT5 at the enhancer not characterized
    • Whether this cooperative repression involves shared cofactors unknown
  11. 2020 High

    Live imaging showing that EMX2 directs opposite centriole migration trajectories in utricular hair cells, and that Notch1a breaks Emx2 symmetry between sibling hair cells in zebrafish, defined how EMX2 asymmetry is both established (upstream regulation) and executed (centriole pre-patterning).

    Evidence GFP-labeled centriole live imaging with ectopic Emx2 electroporation; scRNAseq, lineage tracing, and Notch1a mutagenesis in zebrafish

    PMID:32109392 PMID:32965215

    Open questions at the time
    • Molecular link between EMX2 and centriole migration machinery not identified
    • Whether Notch-mediated asymmetry mechanism applies in mammalian maculae unknown
  12. 2021 High

    Identifying GPR156-Gαi signaling as the downstream effector of EMX2-mediated hair cell reversal established the complete signaling axis: EMX2 polarizes GPR156 distribution, GPR156 signals through Gαi, and this triggers 180° bundle reversal.

    Evidence Conditional Emx2 KO; GPR156 localization and Gαi signaling assays; genetic epistasis in mouse and zebrafish

    PMID:34001891

    Open questions at the time
    • How EMX2 polarizes GPR156 distribution at the molecular level unknown
    • Whether GPR156-Gαi signaling involves additional intermediaries not resolved
  13. 2023 High

    Defining the EMX2→STK32A⊣GPR156 pathway via genetic epistasis with double mutants completed the polarity reversal circuit: EMX2 represses Stk32a transcription, and STK32A normally blocks GPR156 apical localization, so EMX2-positive cells lack STK32A and permit GPR156-mediated reversal.

    Evidence Stk32a KO, Gpr156;Stk32a and Emx2;Stk32a double mutant mice with hair cell polarity and GPR156 localization analysis

    PMID:37144879 PMID:41208475

    Open questions at the time
    • Whether STK32A directly phosphorylates GPR156 or acts indirectly not determined
    • Regulation of Stk32a by EMX2 not confirmed by direct ChIP binding
  14. 2024 High

    Lineage tracing showed that EMX2 is expressed in the prosensory domain before hair cell specification, establishing that LPR positioning is pre-determined by EMX2 expression boundaries prior to hair cell differentiation.

    Evidence Emx2-CreERt2 lineage tracing with tamoxifen induction at multiple developmental stages

    PMID:38682291

    Open questions at the time
    • What signals define the Emx2 expression boundary in the prosensory domain unknown
    • Whether boundary refinement occurs after initial specification not resolved
  15. 2025 Medium

    Identification of Ldb1 as an EMX2 interaction partner by IP-mass spectrometry, with overlapping but distinct target gene sets between EMX2 and Dmrta2, began to define the cofactor landscape through which EMX2 executes transcriptional programs in cortical progenitors.

    Evidence IP-mass spectrometry; ChIP-seq and RNA-seq in mouse cortical tissue

    PMID:40456611

    Open questions at the time
    • Functional requirement for Ldb1 in EMX2-dependent transcription not tested by loss-of-function
    • How EMX2 and Dmrta2 coordinate at shared versus independent targets unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how EMX2 concentration gradients are converted into sharp areal boundaries in the cortex; the molecular mechanism by which EMX2 polarizes GPR156 in hair cells; whether the axonal EMX2-eIF4E interaction has a physiological role in translational control; and the genome-wide direct target repertoire distinguishing EMX2's activating versus repressive functions in different tissues.
  • No genome-wide direct target map integrating ChIP-seq across tissues
  • EMX2-eIF4E functional significance untested
  • Structural basis for EMX2-Pbx1 heterodimer target selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 11 R-HSA-74160 Gene expression (Transcription) 8 R-HSA-162582 Signal Transduction 4
Partners
BRN2DMRT3DMRT5DMRTA2EIF4ELDB1PAX6PBX1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 EMX2 and PAX6, expressed in opposing gradients in the neocortical ventricular zone, cooperate to regulate arealization of the neocortex: rostral areas expand and caudal areas contract in Emx2 mutants, while opposite effects occur in Pax6 mutants, establishing that these two transcription factors specify area identity in opposing manners. Emx2 and Pax6 knockout mice; analysis of molecular markers and area-specific thalamocortical connections Science High 10764649 10862700 12196586
1997 EMX2 is essential for ureteric bud functions in metanephrogenesis: in Emx2 null mice, ureteric bud initially forms and induces Pax-2 in metanephric mesenchyme normally, but subsequently Pax-2, c-ret, Lim1 and GDNF expressions are lost, branching fails to occur, and the bud degenerates; explant co-culture experiments showed the defect is intrinsic to the ureteric bud, not the mesenchyme. Emx2 knockout mice; in situ hybridization; explant co-culture experiments Development High 9165114
1997 EMX2 is required for development of the dentate gyrus, hippocampus, and medial limbic cortex; Emx2 null mice lack dentate gyrus and show reduced hippocampus, with defects initiating in the neuroepithelium from which the dentate gyrus originates. Emx2 knockout mice; histological and cytoarchitectural analysis Development High 10729342 9006071 9012509
2004 EMX2 levels in cortical progenitors directly and disproportionately specify sizes and positions of primary cortical areas: nestin-Emx2 transgenic mice overexpressing EMX2 in cortical progenitors show rostrolateral shift and size reduction of primary sensory/motor areas, while Emx2 heterozygous knockouts show opposite shifts; EMX2 represses PAX6 in rostral progenitors as part of this mechanism. Gain-of-function nestin-Emx2 transgenic mice; Emx2 heterozygous knockout mice; analysis of area-specific molecular markers and thalamocortical projections; Pax6 expression analysis Neuron High 15294144
2003 EMX2 patterns the neocortical area map by regulating FGF8 levels: overexpressing Emx2 alters the area map only when overlapping the FGF8 source; excess Emx2 decreases FGF8 levels, while Emx2 knockout mice show increased FGF8; sequestering excess FGF8 in Emx2 mutants rescues cortical domain shifts, demonstrating that Emx2 acts via indirect regulation of FGF8 positional signaling. Electroporation-mediated gene transfer in vivo; quantification of Fgf8 expression in Emx2 KO and overexpressing embryos; rescue experiment using truncated FGF receptor Nature Neuroscience High 12872126
2002 Wnt and BMP signaling directly regulate Emx2 transcription in the dorsal telencephalon: an enhancer in the mouse Emx2 gene contains Tcf (Wnt mediator) and Smad (BMP mediator) binding sites; mutation of these sites abolishes telencephalic enhancer activity, and ectopic Wnt/BMP signaling leads to ectopic enhancer activation. Transgenic enhancer analysis with lacZ reporter; mutagenesis of Tcf and Smad binding sites; ectopic pathway activation Development High 12070081
2003 EMX2 is a direct transcriptional repressor of Wnt1 in the developing telencephalon: a putative EMX2 DNA-binding site in the Wnt1 enhancer was identified; deletion of this site leads to ectopic Wnt1 expression and leptomeningeal glioneuronal heterotopias similar to those in Emx2-/- mice. Emx2 knockout mice; transgenic mice with deleted EMX2 binding site from Wnt1 enhancer; histological analysis of cortical dysplasia phenotype Development Medium 12668639
2000 EMX2 is required for Reelin signaling in the developing neocortex: Reelin protein is absent from the neocortical marginal zone in Emx2 null mice when the cortical plate is laid down, leading to impaired radial glia development and abnormal neuronal migration patterns in the cortical plate. Emx2 knockout mice; immunohistochemistry for Reelin; analysis of radial glia and neuronal migration Journal of Neuroscience High 10648716
2002 EMX2 promotes symmetric cell divisions in cortical progenitors and instructs a multipotential fate: retroviral transduction of Emx2 in cortical precursors increases large clones generated by symmetric divisions containing multiple cell types (neurons and glia); in Emx2-/- mice, symmetric divisions are reduced. Retroviral Emx2 transduction in cortical precursors; clonal analysis; analysis of Emx2-/- cortex cell division Molecular and Cellular Neurosciences High 11922140
2002 EMX2 regulates proliferation of adult neural stem cells: abolishing Emx2 expression in adult neural stem cells greatly enhances proliferation, while increasing Emx2 reduces it; the mechanism involves regulation of symmetric (stem cell-generating) versus asymmetric divisions, without altering cell cycle length or differentiation capacity. Adult neural stem cell cultures; Emx2 gain- and loss-of-function; cell division mode analysis Development High 11923200
2004 EMX2 protein localizes to axons of olfactory sensory neurons, where it interacts with eukaryotic translation initiation factor 4E (eIF4E): co-immunoprecipitation and pull-down experiments demonstrate direct interaction; Emx2 co-sediments with high-density synaptosomal fractions containing eIF4E, suggesting a non-nuclear role in local translational control in axons. Subcellular fractionation; co-immunoprecipitation; pull-down; immunohistochemistry; chemical lesion experiments PNAS High 15247416
2003 HOXA10 directly represses EMX2 transcription in the reproductive tract: HOXA10 binds a 150-bp element in the EMX2 5' regulatory region (confirmed by EMSA and DNase I footprinting); site-directed mutagenesis of the HOXA10 consensus binding site abolishes both binding and transcriptional repression. Northern blot; in situ hybridization; deletion analysis of EMX2 promoter; EMSA; DNase I footprinting; site-directed mutagenesis; transient transfection assay Molecular and Cellular Biology High 12482956
2010 EMX2 promotes neuronogenesis and inhibits gliogenesis in cortical progenitors: lentiviral overexpression of Emx2 in embryonic cortical progenitors inhibits astrocyte/oligodendrocyte fates and promotes neuronal output, as quantified by multiplex cytofluorometry. Lentiviral overexpression; cytofluorometry with cell-type-specific fluorescent reporters; immunocytofluorescence Stem Cells Medium 20506244
2017 EMX2 controls stereociliary bundle (hair bundle) polarity reversal in mechanosensory hair cells: EMX2 expression is restricted to one side of the line of polarity reversal (LPR) in vestibular maculae and to one sibling hair cell in zebrafish neuromasts; Emx2 mediates the 180° reversal in hair bundle orientation in these restricted subsets, acting cell-autonomously via heterotrimeric G proteins. Emx2 knockout and gain-of-function in mouse and zebrafish; live imaging; immunohistochemistry; genetic epistasis eLife High 28266911
2021 EMX2 controls hair cell orientation via GPR156-Gαi signaling: EMX2 polarizes GPR156 distribution in hair cells, enabling GPR156 to signal through Gαi and trigger a 180° reversal in hair cell orientation; this mechanism is conserved in mouse otolith organs and zebrafish lateral line and is essential for bidirectional sensitivity. Conditional knockout of Emx2; GPR156 localization analysis; Gαi signaling assays; genetic epistasis in mouse and zebrafish Nature Communications High 34001891
2023 EMX2 represses Stk32a transcription, thereby regulating hair bundle polarity: STK32A is expressed complementary to EMX2 at the LPR; Stk32a KO and ectopic expression experiments show it aligns intrinsic polarity with PCP proteins in EMX2-negative regions; EMX2 establishes the LPR boundary by transcriptionally repressing Stk32a, which controls the apical localization of GPR156. Stk32a and Emx2 knockout mice; genetic epistasis (Gpr156;Stk32a and Emx2;Stk32a double mutants); hair cell polarity analysis; GPR156 localization eLife High 37144879
2025 EMX2 represses Stk32a transcription, allowing GPR156-mediated bundle reversal in one hair cell group; in the utricle, GPR156 reverses stereociliary bundles relative to the PCP axis but is blocked by STK32A; EMX2 establishes the LPR boundary by repressing Stk32a. Similar functional relationships hold in the cochlea. Genetic epistasis experiments with Gpr156;Stk32a and Emx2;Stk32a combined mutant mice; stereociliary bundle orientation analysis Journal of Cell Science High 41208475
2018 EMX2 regulates afferent neuron directional selectivity in zebrafish neuromasts via two mechanisms: (1) reversing hair bundle orientation in half of hair cells (previously established), and (2) determining which hair cells afferent neurons innervate; in emx2 KO and gain-of-function neuromasts, all HCs are unidirectional and innervation patterns depend on Emx2 presence. emx2 knockout and gain-of-function in zebrafish; calcium imaging of afferent responses; anatomical tracing of innervation eLife High 29671737
2020 EMX2 pre-patterns hair cells prior to centriole migration to establish opposite bundle orientations: live imaging of GFP-labeled centrioles shows centrioles migrate toward opposite directions in the two utricular regions; ectopic Emx2 reverses centriole trajectory within hours during a critical time-window, indicating EMX2 acts upstream of centriole migration. Live imaging of GFP-labeled centrioles in embryonic utricles; ectopic Emx2 electroporation with time-lapse analysis eLife High 32965215
2020 Epithelial planar bipolarity in zebrafish neuromasts is established by asymmetric Emx2 expression initiated in hair cell progenitors and subsequently repressed in one sibling hair cell by Notch1a receptor signaling; Emx2 asymmetry is not due to auto-regulatory feedback, and Emx2 deficiency causes all hair cells to adopt identical orientation. Single-cell RNA sequencing; diffusion pseudotime analysis; lineage tracing; mutagenesis; Notch1a receptor analysis Current Biology High 32109392
2002 EMX2 and PAX6 are necessary for the specification of cortical versus ganglionic identity in the dorsal telencephalon: high-level expression of at least one functional allele of either Emx2 or Pax6 is necessary and sufficient to activate cortical morphogenesis and repress adjacent striatal fate; in Emx2-/-;Pax6(Sey/Sey) double mutants, the dorsal telencephalon is converted into basal ganglia. Emx2/Pax6 double knockout mice; molecular marker analysis of cortical vs. ganglionic identity Nature Neuroscience High 12118260
2010 EMX2 suppresses EGFR expression in gonadal epithelial cells and regulates tight junction assembly: Emx2 KO embryonic gonads show upregulation of Egfr (confirmed by microarray and cultured M15 cells), increased Src and EGFR tyrosine phosphorylation, aberrant tight junctions, and impaired epithelial cell migration to mesenchyme. Emx2 KO mice; microarray; in vitro M15 cell culture with Emx2 expression; immunofluorescence for tight junction proteins and phospho-Src/EGFR Endocrinology Medium 20962046
2010 EMX2 directly represses Sox2 telencephalic enhancers: Emx2 protein binds overlapping Emx2/POU binding sites in Sox2 enhancers (demonstrated by EMSA), prevents binding of POU activator Brn2, and directly interacts with Brn2 protein; loss of one Emx2 allele increases Sox2 levels in the hippocampal primordium and rescues hippocampal neurogenesis in hypomorphic Sox2 mutants. EMSA; transfection reporter assays; Emx2 haploinsufficiency analysis in Sox2 hypomorphs; transgene expression analysis Nucleic Acids Research High 22495934
2010 A mutual stimulating loop between Emx2 and canonical Wnt signaling specifically promotes expansion of the occipito-hippocampal anlage; in Emx2-/- mutants, progenitors exit the cell cycle prematurely due to misregulation of cell cycle, proneural, and lateral inhibition molecular machineries; reactivation of canonical Wnt signaling rescues molecular abnormalities and corrects differentiation rates. Emx2 KO mice; Wnt pathway activation in Emx2 mutants; gene expression analysis of cell cycle regulators Cerebral Cortex Medium 15800025
2011 Human teneurin-1 is a direct transcriptional target of EMX2: EMX2 induces transcription from a newly identified alternative promoter of teneurin-1 that contains a homeobox binding site; mutagenesis of this site reduces promoter activity in vitro and in vivo; direct in vivo binding of EMX2 to this promoter element was demonstrated. 5'RACE; promoter-reporter assays; mutagenesis; in vivo ChIP; in ovo electroporation in chick BMC Developmental Biology High 21651764
2010 Emx2 regulates early cochlear development including hair cell number, supporting cell differentiation, and cochlear length: Emx2 null mice have ~60% fewer auditory hair cells, appear to lack outer hair cells, show expanded Bmp4 domain and reduced Fgfr1 and Prox1 expression in cochlear sensory epithelium; vestibular planar cell polarity is unaffected but polarity reversal across the striola is absent. Emx2 knockout mice; hair cell counting; immunohistochemistry; polarity measurements; in situ hybridization for Bmp4, Fgfr1, Prox1 Developmental Biology Medium 20152827
2010 Pbx1 and Emx2 physically interact as heterodimers binding specific DNA sequences and cooperatively activate Alx1 transcription: Pbx1 and Emx2 bind in vivo to a conserved sequence upstream of Alx1 and cooperatively activate transcription via this regulatory element, with Alx1 expression absent in all compound Pbx/Emx2 mutants. Compound mutant mouse analysis; heterodimer DNA binding assay; in vivo ChIP at Alx1 regulatory element; reporter assay Development High 20627960
2011 Pax2 is a direct upstream regulator of Emx2 expression in the Wolffian duct: Pax2+/-;Emx2+/- compound heterozygous mice show high incidence of CAKUT-like urinary tract anomalies, and Pax2 is identified as a direct regulator of Emx2 expression. Compound heterozygous mouse model; early embryo analysis of ureter budding; Pax2 regulation of Emx2 expression PloS One Medium 21731775
2005 EMX2 regulates endometrial cell proliferation to control implantation: intrauterine overexpression of Emx2 reduces implantation rate ~40% and decreases PCNA expression and BrdU incorporation in endometrial cells; Emx2 reduces cell number in human endometrial epithelial cells in vitro, without affecting differentiation or apoptosis markers. Intrauterine lipofection of Emx2 expression construct; PCNA and BrdU incorporation assays; in vitro human endometrial cell proliferation assay Molecular Endocrinology Medium 15994197
2018 DMRT3, DMRT5, and EMX2 cooperatively repress Gsx2 at the pallium-subpallium boundary to maintain cortical identity: both DMRT3, DMRT5, and EMX2 bind to a ventral telencephalon-specific enhancer in the Gsx2 locus; Emx2;Dmrt5 double KO phenotype resembles Dmrt3;Dmrt5 double KO with ventralized dorsal telencephalon. Single and double KO mice; Dmrt5 overexpression in ventral telencephalon; chromatin binding assay at Gsx2 enhancer Journal of Neuroscience High 30143575
2025 EMX2 coordinates with LIM domain-binding protein Ldb1 to execute activation and repression of downstream targets in cortical progenitors: co-immunoprecipitation and interaction partner identification identified Ldb1 as an EMX2 interaction partner; EMX2 and Dmrta2 regulate a similar set of genes but have limited common direct targets including key cortical development regulators. Immunoprecipitation/mass spectrometry to identify EMX2 interaction partners; ChIP-seq; RNA-seq; mouse genetic models Journal of Neuroscience Medium 40456611
2010 Emx2 antisense RNA (Emx2OS) contributes to post-transcriptional downregulation of Emx2 sense mRNA in cortical precursors, possibly by a Dicer-promoted mechanism; conversely, Emx2 KO dramatically impairs Emx2OS transcription, indicating a reciprocal regulatory loop between Emx2 and its antisense transcript at the same locus. Lentiviral gene delivery; RNAi; TetON technology; morpholino knockdown; quantitative RT-PCR in primary CNS precursor cultures PloS One Medium 20066053
2016 EMX2 is required for male gonocyte differentiation via regulation of the FGF9/NODAL pathway: in conditional Emx2-knockdown testes, FGF9 and NODAL signaling are maintained at abnormally high levels, preventing G1/G0 arrest and pluripotency marker downregulation; blocking FGF9 with SU5402 or NODAL with SB431542 rescues germ cell differentiation in vitro. Tamoxifen-inducible Cre-loxP Emx2 knockdown; FGF9 and NODAL inhibitors (SU5402, SB431542); germ cell colony formation assays; pluripotency marker analysis Reproduction Medium 27002001
2024 Emx2 is an essential regulator of ciliogenesis across embryonic tissues including ear, neuromasts, and Kupffer's vesicle: emx2-deficient zebrafish embryos show decreased multiciliated cells in kidney, aberrant basal body positioning, and disrupted renal monociliated cells; mechanistically, Emx2 regulates prostaglandin biosynthesis (via ppargc1a, ptgs1, and PGE2) as part of its ciliogenesis regulatory role. emx2 loss-of-function in zebrafish; multiciliated cell quantification; basal body positioning analysis; prostaglandin biosynthesis gene expression iScience Medium 39687012
1999 Yeast two-hybrid screening identified Cnot6l and QkI-7 as novel EMX2-binding partners; these proteins are involved in mRNA metabolism including splicing, mRNA export, translation, and mRNA destruction. Yeast two-hybrid screen using embryonic mouse cDNA library The Protein Journal Low 30628007
2024 EMX2 lineage tracing reveals that Emx2 is expressed before hair cell specification in the prosensory domain, and precursors labeled at this stage give rise to hair cells on one side of the LPR in the mature utricle/saccule, indicating LPR positioning is pre-determined in the prosensory domain before hair cell specification. Emx2-CreERt2 transgenic lineage tracing; tamoxifen induction at different developmental stages; analysis in Dreher mutants Development High 38682291

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. Science (New York, N.Y.) 434 10764649
1997 Defects of urogenital development in mice lacking Emx2. Development (Cambridge, England) 340 9165114
1997 Emx1 and Emx2 functions in development of dorsal telencephalon. Development (Cambridge, England) 312 9006071
1996 Dentate gyrus formation requires Emx2. Development (Cambridge, England) 214 9012509
2000 Area identity shifts in the early cerebral cortex of Emx2-/- mutant mice. Nature neuroscience 201 10862700
2002 Distinct actions of Emx1, Emx2, and Pax6 in regulating the specification of areas in the developing neocortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 187 12196586
1996 Emx1 and Emx2 show different patterns of expression during proliferation and differentiation of the developing cerebral cortex in the mouse. The European journal of neuroscience 176 8743751
2004 EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors. Neuron 173 15294144
2002 Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon. Development (Cambridge, England) 156 12070081
2003 Emx2 patterns the neocortex by regulating FGF positional signaling. Nature neuroscience 146 12872126
2002 Emx2 and Pax6 control regionalization of the pre-neuronogenic cortical primordium. Cerebral cortex (New York, N.Y. : 1991) 136 11739261
2003 Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding. The Journal of comparative neurology 126 12561075
2002 Conversion of cerebral cortex into basal ganglia in Emx2(-/-) Pax6(Sey/Sey) double-mutant mice. Nature neuroscience 122 12118260
2002 Emx2 regulates the proliferation of stem cells of the adult mammalian central nervous system. Development (Cambridge, England) 114 11923200
2000 The lack of Emx2 causes impairment of Reelin signaling and defects of neuronal migration in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 114 10648716
1998 EMX2 protein in the developing mouse brain and olfactory area. Mechanisms of development 110 9831645
2008 Frontal cortex subdivision patterning is coordinately regulated by Fgf8, Fgf17, and Emx2. The Journal of comparative neurology 107 18459137
1997 Familial schizencephaly associated with EMX2 mutation. Neurology 107 9153481
2003 Transcriptional repression of peri-implantation EMX2 expression in mammalian reproduction by HOXA10. Molecular and cellular biology 106 12482956
2001 Emx2 promotes symmetric cell divisions and a multipotential fate in precursors from the cerebral cortex. Molecular and cellular neurosciences 93 11922140
2017 Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells. eLife 91 28266911
2010 Emx2 and Foxg1 inhibit gliogenesis and promote neuronogenesis. Stem cells (Dayton, Ohio) 89 20506244
2000 Emx2 is required for growth of the hippocampus but not for hippocampal field specification. The Journal of neuroscience : the official journal of the Society for Neuroscience 87 10729342
2003 Emx1, emx2 and pax6 in specification, regionalization and arealization of the cerebral cortex. Cerebral cortex (New York, N.Y. : 1991) 81 12764040
2007 Genetic interplay between the transcription factors Sp8 and Emx2 in the patterning of the forebrain. Neural development 80 17470284
2005 Emx2 and Pax6 function in cooperation with Otx2 and Otx1 to develop caudal forebrain primordium that includes future archipallium. The Journal of neuroscience : the official journal of the Society for Neuroscience 79 15917450
2004 Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 75 15247416
2010 Abnormal epithelial cell polarity and ectopic epidermal growth factor receptor (EGFR) expression induced in Emx2 KO embryonic gonads. Endocrinology 67 20962046
2002 Emx2: a gene responsible for cortical development, regionalization and area specification. Gene 66 12095673
2005 A mutually stimulating loop involving emx2 and canonical wnt signalling specifically promotes expansion of occipital cortex and hippocampus. Cerebral cortex (New York, N.Y. : 1991) 63 15800025
2002 Role of Emx2 in the development of the reciprocal connectivity between cortex and thalamus. The Journal of comparative neurology 63 12209834
2008 Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development. The European journal of neuroscience 61 18973570
1997 A number of schizencephaly patients including 2 brothers are heterozygous for germline mutations in the homeobox gene EMX2. European journal of human genetics : EJHG 60 9359037
2001 Emx2 directs the development of diencephalon in cooperation with Otx2. Development (Cambridge, England) 58 11493561
2010 Emx2 and early hair cell development in the mouse inner ear. Developmental biology 57 20152827
2004 Emx1 and Emx2 cooperate in initial phase of archipallium development. Mechanisms of development 56 15147765
2010 Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1. Development (Cambridge, England) 53 20627960
2006 Potential target genes of EMX2 include Odz/Ten-M and other gene families with implications for cortical patterning. Molecular and cellular neurosciences 52 16919471
2001 Agenesis of the scapula in Emx2 homozygous mutants. Developmental biology 51 11254354
2005 Emx2 regulates mammalian reproduction by altering endometrial cell proliferation. Molecular endocrinology (Baltimore, Md.) 50 15994197
2021 EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia. Nature communications 49 34001891
2003 Loss of Emx2 function leads to ectopic expression of Wnt1 in the developing telencephalon and cortical dysplasia. Development (Cambridge, England) 49 12668639
1997 Emx2 developmental expression in the primordia of the reproductive and excretory systems. Anatomy and embryology 48 9453363
2010 EMX2 is epigenetically silenced and suppresses growth in human lung cancer. Oncogene 47 20697358
2001 Emx2 in adult neural precursor cells. Mechanisms of development 39 11731244
2010 Regulation of Emx2 expression by antisense transcripts in murine cortico-cerebral precursors. PloS one 38 20066053
2022 Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2. Nature communications 37 36280667
2003 Antisense transcripts at the EMX2 locus in human and mouse. Genomics 36 12573261
2011 A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype. Neural development 34 21214893
2001 Characterization of the homeodomain gene EMX2: sequence conservation, expression analysis, and a search for mutations in endometrial cancers. Genomics 31 11549315
2018 DMRT5, DMRT3, and EMX2 Cooperatively Repress Gsx2 at the Pallium-Subpallium Boundary to Maintain Cortical Identity in Dorsal Telencephalic Progenitors. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 30143575
2008 No major role for the EMX2 gene in schizencephaly. American journal of medical genetics. Part A 30 18409201
2007 Variants in EMX2 and PTEN do not contribute to risk of endometriosis. Molecular human reproduction 30 17563403
2006 The transcription factors Emx1 and Emx2 suppress choroid plexus development and promote neuroepithelial cell fate. Developmental biology 28 16793035
2020 Epithelial Planar Bipolarity Emerges from Notch-Mediated Asymmetric Inhibition of Emx2. Current biology : CB 27 32109392
2003 The homeobox gene Emx2 underlies middle ear and inner ear defects in the deaf mouse mutant pardon. Journal of neurocytology 27 15044845
2018 Directional selectivity of afferent neurons in zebrafish neuromasts is regulated by Emx2 in presynaptic hair cells. eLife 25 29671737
2004 The role of Emx2 during scapula formation. Developmental biology 25 15501221
2012 Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers. Nucleic acids research 24 22495934
2011 Control of pelvic girdle development by genes of the Pbx family and Emx2. Developmental dynamics : an official publication of the American Association of Anatomists 22 21455939
2011 Vesicoureteral reflux and other urinary tract malformations in mice compound heterozygous for Pax2 and Emx2. PloS one 22 21731775
2010 The same enhancer regulates the earliest Emx2 expression in caudal forebrain primordium, subsequent expression in dorsal telencephalon and later expression in the cortical ventricular zone. Development (Cambridge, England) 22 20667915
2018 Wnt and BMP signaling pathways co-operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2. Journal of cellular biochemistry 21 30450775
2011 Downregulation of EMX2 is associated with clinical outcomes in lung adenocarcinoma patients. Clinical lung cancer 21 21726823
2015 Nonsense mutation of EMX2 is potential causative for uterus didelphysis: first molecular explanation for isolated incomplete müllerian fusion. Fertility and sterility 20 25577462
2003 Cloning and cortical expression of rat Emx2 and adenovirus-mediated overexpression to assess its regulation of area-specific targeting of thalamocortical axons. Cerebral cortex (New York, N.Y. : 1991) 19 12764041
2013 EMX2 is downregulated in endometrial cancer and correlated with tumor progression. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 18 23370654
2012 Adenoviral delivery of the EMX2 gene suppresses growth in human gastric cancer. PloS one 18 23029345
2024 Emx2 underlies the development and evolution of marsupial gliding membranes. Nature 17 38658750
2015 EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas. PloS one 17 26132438
2016 Emx2 as a novel tool to suppress glioblastoma. Oncotarget 16 27191499
2020 Emx2 regulates hair cell rearrangement but not positional identity within neuromasts. eLife 15 33377867
2018 Cohesive Regulation of Neural Progenitor Development by microRNA miR-26, Its Host Gene Ctdsp and Target Gene Emx2 in the Mouse Embryonic Cerebral Cortex. Frontiers in molecular neuroscience 15 29515367
2016 HOXA10, EMX2 and TENM1 expression in the mid-secretory endometrium of infertile women with a Müllerian duct anomaly. Reproductive biomedicine online 15 26896429
1998 Graded expression of Emx-2 in the adult newt limb and its corresponding regeneration blastema. Journal of molecular biology 15 9641974
2011 Human teneurin-1 is a direct target of the homeobox transcription factor EMX2 at a novel alternate promoter. BMC developmental biology 14 21651764
2021 Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2. Cell death & disease 13 34016958
2018 The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line. BMC cancer 13 30514244
2023 The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear. eLife 11 37144879
2021 Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis. Journal of experimental & clinical cancer research : CR 11 34364391
2020 Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2. eLife 11 32965215
2015 Identification and expression of the target gene emx2 of miR-26a and miR-26b in Paralichthys olivaceus. Gene 11 26079439
2006 Emx2 in the developing hippocampal fissure region. The European journal of neuroscience 11 16819978
2002 Impaired postnatal development of hippocampal neurons and axon projections in the Emx2-/- mutants. Journal of neurochemistry 11 12437591
2019 EMX2 is epigenetically silenced and suppresses epithelial‑mesenchymal transition in human esophageal adenocarcinoma. Oncology reports 10 31432154
2016 Empty Spiracles Homeobox 2 (EMX2) Inhibits the Invasion and Tumorigenesis in Colorectal Cancer Cells. Oncology research 10 27712600
2016 Critical role of Emx2 in the pluripotency - differentiation transition in male gonocytes via regulation of FGF9/NODAL pathway. Reproduction (Cambridge, England) 9 27002001
2013 Promotion of cortico-cerebral precursors expansion by artificial pri-miRNAs targeted against the Emx2 locus. Current gene therapy 9 23317055
1999 Mutation analysis of the EMX2 gene in Kallmann's syndrome. Fertility and sterility 8 10560999
2021 Binding of microRNA-135a (miR-135a) to homeobox protein A10 (HOXA10) mRNA in a high-progesterone environment modulates the embryonic implantation factors beta3-integrin (ITGβ3) and empty spiracles homeobox-2 (EMX2). Annals of translational medicine 7 33987360
2022 An Association between EMX2 Variations and Mayer-Rokitansky-Küster-Hauser Syndrome: A Case-Control Study of Chinese Women. Journal of healthcare engineering 5 35463657
1999 Mouse forebrain development. The role of Emx2 homeobox gene. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie 5 10609088
2024 EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway. Molecular carcinogenesis 4 38362840
2024 Emx2 lineage tracing reveals antecedent patterns of planar polarity in the mouse inner ear. Development (Cambridge, England) 4 38682291
2024 CRISPR/dCas9-Mediated DNA Methylation Editing on emx2 in Chinese Tongue Sole (Cynoglossus semilaevis) Testis Cells. International journal of molecular sciences 3 39062879
2025 Novel Insights into Emx2 and Dmrta2 Cooperation during Cortex Development and Evidence for Dmrta2 Function in the Choroid Plexus. The Journal of neuroscience : the official journal of the Society for Neuroscience 1 40456611
2024 Emx2 is an essential regulator of ciliated cell development across embryonic tissues. iScience 1 39687012
2019 Identification of Novel Binding Partners for Transcription Factor Emx2. The protein journal 1 30628007
2025 Planar polarized organization of mouse hair cells is established and maintained by STK32A, GPR156 and EMX2. Journal of cell science 0 41208475
2022 The tissue-specificity associated region and motif of an emx2 downstream enhancer CNE2.04 in zebrafish. Gene expression patterns : GEP 0 35970322