Affinage

LMX1B

LIM homeobox transcription factor 1-beta · UniProt O60663

Length
402 aa
Mass
44.9 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LMX1B is a LIM-homeodomain transcription factor that binds AT-rich FLAT elements and gene-specific cis-regulatory modules to directly activate or repress target genes across limb, neural, ocular, and renal development (PMID:11175791, PMID:11956244, PMID:11956245, PMID:28455377). In the limb, Lmx1b is essential for specification of dorsal fates, acting cell-autonomously in skeletal progenitors and amplified through conserved Lmx1b-bound regulatory modules (LARM1/LARM2) that sustain its own expression (PMID:9590288, PMID:9590287, PMID:20215352, PMID:34545091). At the midbrain-hindbrain isthmic organizer it sits atop a regulatory cascade controlling Wnt1, Fgf8, En1 and Pax2, with Wnt1 maintenance and tectum/cerebellum development depending on Lmx1b (PMID:10751174, PMID:17166916, PMID:12399317). In dopaminergic and serotonergic neurons, Lmx1b (cooperating with Lmx1a, Foxa1/2, and Pet1) drives both initial specification and lifelong maintenance of neuronal identity, neurotransmitter biosynthesis genes, and axonal projection patterning (PMID:10725922, PMID:12897786, PMID:14602809, PMID:21880902, PMID:21246047, PMID:31355748). In adult midbrain dopaminergic neurons it additionally sustains the autophagic-lysosomal pathway and mitochondrial integrity, and its own stability and transcriptional output are reciprocally controlled by ATG8/LC3 binding, forming a feedback loop protective against oxidative and proteostatic stress (PMID:25915474, PMID:27407143, PMID:37014324). In kidney podocytes, Lmx1b directly regulates collagen IV (COL4A3/4), podocin (NPHS2) and CD2AP—often combinatorially with FoxC2—to build the glomerular basement membrane and slit diaphragm (PMID:11175791, PMID:11956244, PMID:11956245, PMID:24854274), and it acts as an anti-osteogenic factor by repressing Runx2 in calvarial and osteoblast mesenchyme (PMID:29852132, PMID:35563615). Human LMX1B haploinsufficiency through loss of DNA-binding and transactivation causes nail-patella syndrome with associated glaucoma (PMID:9590287, PMID:9618165).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 High

    Established that Lmx1b is required for dorsal limb identity and that human loss-of-function underlies a Mendelian disease, defining LMX1B as a developmental master regulator.

    Evidence Targeted knockout mice with skeletal phenotyping and patient mutation sequencing with in vitro DNA-binding assays

    PMID:9590287 PMID:9590288 PMID:9618165

    Open questions at the time
    • Direct transcriptional targets in the limb not yet identified
    • Mechanism of haploinsufficiency vs dominant-negative not yet dissected
  2. 2000 High

    Defined Lmx1b's position upstream of Wnt1 in the isthmic organizer cascade and its requirement for dopaminergic neuron and anterior eye development, extending its role beyond the limb.

    Evidence Chick retroviral misexpression with Fgf8 beads, in situ hybridization, and knockout mouse analysis of midbrain, eye, and TH+ neurons

    PMID:10660670 PMID:10725922 PMID:10751174

    Open questions at the time
    • Whether Wnt1 induction is direct or indirect not resolved
    • Direct DNA targets in neural tissue not identified
  3. 2001 High

    Demonstrated direct transcriptional control of glomerular basement membrane collagen, linking LMX1B molecular function to the renal phenotype of NPS.

    Evidence EMSA and reporter assays on a COL4A4 intronic enhancer plus knockout mouse collagen analysis

    PMID:11175791

    Open questions at the time
    • Full set of renal targets not yet defined
    • In vivo enhancer occupancy not shown by ChIP
  4. 2002 High

    Identified the FLAT element as the LMX1B-bound motif in the podocin promoter and tied podocyte slit-diaphragm gene expression to LMX1B, explaining glomerular failure in NPS.

    Evidence EMSA, co-transfection reporters, and Lmx1b knockout podocyte immunohistochemistry

    PMID:11956244 PMID:11956245

    Open questions at the time
    • Combinatorial cofactors at podocyte enhancers not yet identified
    • Adult vs developmental requirement not separated
  5. 2000 Medium

    Showed that LMX1B transactivation is modulated by cofactors and that NPS homeodomain mutants are simple loss-of-function rather than dominant-negative, clarifying the genetic mechanism of disease.

    Evidence Co-transfection reporter assays with E47 and LDB1 and mutant mixing experiments

    PMID:10767331

    Open questions at the time
    • Single-lab transfection assay
    • Endogenous relevance of E47 synergy not validated in vivo
  6. 2003 High

    Defined Lmx1b as a master regulator of central serotonergic neuron specification, placing it within the Nkx2-2 → Lmx1b → Pet1 hierarchy.

    Evidence Knockout mice, genetic epistasis, and gain-of-function ectopic expression in spinal cord

    PMID:12897786 PMID:14602809

    Open questions at the time
    • Direct vs indirect regulation of 5-HT synthesis genes not resolved
    • Cofactors mediating combinatorial specification unknown
  7. 2004 High

    Extended Lmx1b's role to dorsal horn sensory neuron differentiation and migration, identifying downstream activated and repressed transcription factor targets.

    Evidence Knockout mouse in situ hybridization and immunohistochemistry of dorsal horn markers

    PMID:15229182

    Open questions at the time
    • Direct DNA binding to Rnx/Drg11/Zic loci not shown
    • Mechanism of afferent ingrowth defect unclear
  8. 2006 High

    Distinguished maintenance from specification by showing postnatal Lmx1b is continuously required to keep serotonergic neurons alive and differentiated, and confirmed its requirement for the full MHB gene cascade.

    Evidence Cell-type-specific and conditional Cre-lox knockouts with marker and survival analysis

    PMID:17151281 PMID:17166916

    Open questions at the time
    • Molecular trigger of neuronal death after Lmx1b loss not defined
    • Direct targets among Tph2/Sert not proven by occupancy
  9. 2007 High

    Revealed a non-developmental gene-regulatory mode in which LMX1B cooperates with NF-κB to drive inflammatory cytokine transcription.

    Evidence Inducible expression, microarray, ChIP, reporter assays, and siRNA knockdown

    PMID:18996370

    Open questions at the time
    • Physiological context of LMX1B/NF-κB cooperation in disease unclear
    • Direct protein-protein contact with NF-κB not demonstrated
  10. 2008 Medium

    Began assembling the LMX1B protein interaction network in dopaminergic cells by identifying PSPC1/PSF as a transcriptional complex partner.

    Evidence Affinity purification-mass spectrometry and reciprocal co-IP in MN9D cells and in vivo

    PMID:23308148

    Open questions at the time
    • Functional consequence of PSPC1 binding on target genes not established
    • Single-lab interaction
  11. 2011 High

    Defined cooperative and adult-maintenance functions of Lmx1b with Lmx1a in dopaminergic progenitors and in adult serotonergic neurotransmitter biosynthesis.

    Evidence Compound and inducible conditional knockouts with gene expression analysis and HPLC measurement of 5-HT

    PMID:21246047 PMID:21752929 PMID:21880902

    Open questions at the time
    • Redundancy boundaries between Lmx1a and Lmx1b incompletely mapped
    • Direct targets controlling cell-cycle exit not confirmed by occupancy
  12. 2013 High

    Linked LMX1B to direct podocyte cytoskeletal-gene regulation and to an autoregulatory miRNA feedback loop modulating Wnt signaling.

    Evidence Inducible podocyte knockout, ChIP and EMSA on ABRA/ARL4C, zebrafish knockdown, and luciferase validation of miR135a2 targeting

    PMID:23990680 PMID:24348261

    Open questions at the time
    • Scope of miRNA feedback in other tissues unknown
    • Mechanism coupling ABRA/ARL4C to actin defects not detailed
  13. 2014 High

    Reconciled disease mechanism by showing that a specific DNA-binding-dead mutant acts dominant-negatively through LDB1-mediated dimerization, and established combinatorial podocin regulation with FoxC2.

    Evidence ENU mutant mice with co-IP and transgenic rescue, plus zebrafish enhancer mapping with EMSA and FoxC2 co-overexpression

    PMID:24809698 PMID:24854274

    Open questions at the time
    • Why most NPS alleles are pure loss-of-function while V265D is dominant-negative not fully generalized
    • Stoichiometry of LMX1B-LDB1-FoxC complexes unresolved
  14. 2015 High

    Identified an adult survival function in which Lmx1a/b sustain autophagic-lysosomal clearance, with loss producing α-synuclein inclusions and dopaminergic degeneration.

    Evidence Adult conditional double knockout with autophagy pathway and neuronal counting analysis

    PMID:25915474

    Open questions at the time
    • Direct autophagy gene targets not enumerated
    • Lmx1b-specific contribution vs Lmx1a not separated
  15. 2016 High

    Extended the adult dopaminergic role to mitochondrial homeostasis, showing Lmx1a/b control respiratory chain function and limit oxidative damage.

    Evidence Conditional double knockout with respiration assays, ROS measurement, and mtDNA damage analysis

    PMID:27407143

    Open questions at the time
    • Direct mitochondrial gene targets not defined
    • Lmx1b-only requirement not isolated
  16. 2017 High

    Provided genome-wide occupancy maps in limb and identified repression of axon-guidance receptor Plxnc1, mechanistically grounding LMX1B targeting at active regulatory elements.

    Evidence ChIP-seq in embryonic limb with in vivo CRM validation, and conditional knockout with ChIP-seq for Plxnc1 regulation

    PMID:28455377 PMID:29038581

    Open questions at the time
    • Functional impact of most of the ~617 bound intervals untested
    • Activator vs repressor determinants at individual sites unclear
  17. 2018 High

    Defined an anti-osteogenic function for Lmx1b in calvarial mesenchyme, with loss causing heterotopic ossification and craniosynostosis.

    Evidence Head-mesenchyme-specific conditional knockout and gain-of-function transgenic mice with calvarial phenotyping

    PMID:29852132

    Open questions at the time
    • Direct anti-osteogenic targets not yet identified in this study
    • Relationship to NPS bone phenotypes unclear
  18. 2019 High

    Showed Lmx1b governs successive stages of serotonergic axon outgrowth, routing, and arborization via a temporally controlled Lmx1b→Pet1 cascade.

    Evidence Stage-specific conditional targeting with axon morphology and target-gene analysis

    PMID:31355748

    Open questions at the time
    • Direct binding to Protocadherin-αc2 not shown
    • Stage-specific cofactors unidentified
  19. 2021 High

    Demonstrated that limb-specific enhancers (LARM1/LARM2) directly bound by Lmx1b amplify its expression and are themselves mutated in NPS patients lacking coding mutations, expanding the disease mechanism to regulatory elements.

    Evidence ChIP, CRISPR enhancer knockout, in vivo reporter assays, and patient variant identification

    PMID:34545091

    Open questions at the time
    • Whether analogous regulatory modules operate in non-limb tissues unknown
    • Quantitative threshold of Lmx1b dosage for dorsalization undefined
  20. 2022 Medium

    Provided a molecular basis for anti-osteogenesis by showing LMX1B physically binds and represses Runx2, reducing its promoter recruitment during BMP2-induced osteoblast differentiation.

    Evidence Co-IP, ChIP, gain/loss-of-function in osteoblast precursors, and in vivo ectopic bone assay

    PMID:35563615

    Open questions at the time
    • Single-lab interaction
    • Direct DNA binding vs tethered repression at Runx2 targets not distinguished
  21. 2023 High

    Established a reciprocal regulatory loop in which autophagy controls LMX1B protein stability while ATG8/LC3 binding stimulates LMX1B-mediated transcription, integrating its proteostatic and transcriptional roles in human dopaminergic neurons.

    Evidence iPSC-derived mDA neurons with co-IP of LMX1B and ATG8 proteins, fractionation, and rotenone toxicity and respiration assays

    PMID:37014324

    Open questions at the time
    • LIR motif and binding determinants not fully mapped
    • In vivo relevance to Parkinson's disease pathology untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LMX1B selects between activator and repressor outputs at its genome-wide binding sites, and which cofactors dictate tissue-specific target choice, remains unresolved.
  • No unified model linking ChIP-seq occupancy to activation vs repression
  • Tissue-specific cofactor logic incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9612973 Autophagy 2
Partners
E47FOXC2LDB1PAX2PSPC1RUNX2

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Targeted disruption of Lmx1b in mice causes absence of dorsal limb structures (nails, patellae), demonstrating Lmx1b is essential for specification of dorsal limb fates; limb phenotype mirrors nail patella syndrome (NPS). Targeted gene disruption (knockout mice) with skeletal phenotypic analysis Nature genetics High 9590287 9590288
1998 NPS-causing LMX1B mutations include missense mutations that disrupt sequence-specific DNA binding and nonsense mutations causing premature translation termination, establishing LMX1B haploinsufficiency as the pathogenic mechanism. Patient mutation sequencing; functional DNA-binding assay in vitro Nature genetics High 9590287 9618165
1998 LMX1B mutations causing NPS are loss-of-function (two stop codons, a frameshift deletion, and a missense in a functionally important homeodomain residue), confirming haploinsufficiency underlies NPS including glaucoma. Genomic sequencing of NPS patients; structural inference of missense impact on DNA-binding homeodomain Human molecular genetics High 9618165
2000 LMX1B transactivation is synergistically enhanced by co-transfection with E47/shPan1 (a helix-loop-helix protein), while LDB1 (a LIM domain-interacting protein) down-regulates LMX1B-mediated transactivation; LMX1B homeodomain mutations abolish transactivation and do not act as dominant negatives. Co-transfection reporter assays; mutant LMX1B mixing experiments Human molecular genetics Medium 10767331
2001 LMX1B directly binds a putative enhancer sequence in intron 1 of both mouse and human COL4A4 and upregulates reporter constructs containing this enhancer, thereby regulating coordinated expression of alpha3(IV) and alpha4(IV) collagen in the glomerular basement membrane. Gel shift (EMSA) and reporter transfection assay; Lmx1b knockout mouse collagen expression analysis Nature genetics High 11175791
2002 LMX1B binds two AT-rich sequences (FLAT elements) in the promoter region of NPHS2 (podocin) by gel shift assay and activates transcription through them in co-transfection assays; Lmx1b-/- podocytes have greatly reduced CD2AP and podocin levels, lack slit diaphragms, and have reduced foot processes. Gel shift (EMSA); co-transfection reporter assay; Lmx1b knockout mouse analysis; immunohistochemistry The Journal of clinical investigation High 11956244 11956245
2000 Lmx1b maintains Wnt1 expression at the isthmic organizer (IsO): Fgf8 induces Lmx1b expression, and retroviral ectopic expression of Lmx1b maintains Wnt1 expression in the mesencephalon, placing Lmx1b upstream of Wnt1 in the IsO gene cascade. In situ hybridization; retroviral (RCAS) ectopic expression; Fgf8-soaked bead implantation experiments in chick Development (Cambridge, England) High 10751174
2000 Lmx1b is required for normal anterior segment eye development; homozygous Lmx1b mutant mice display iris and ciliary body hypoplasia, corneal stromal defects, and aberrant expression of corneal genes (mf1, mfh1 persistent; keratocan absent), indicating Lmx1b regulates anterior segment morphogenesis. Targeted knockout mice; in situ hybridization; ultrastructural analysis Genesis High 10660670
2000 Lmx1b is required for a second molecular cascade in mesencephalic dopamine (mesDA) neuron development: Lmx1b null mice fail to induce Ptx3 in TH-positive neurons, and this small set of TH-positive neurons is subsequently lost during embryonic maturation. Lmx1b knockout mouse analysis; spatiotemporal expression studies; immunohistochemistry Nature neuroscience High 10725922
2003 Lmx1b is required for development of all central serotonergic (5-HT) neurons: Lmx1b null mice lose expression of genes necessary for serotonin synthesis and transport. Lmx1b acts downstream of Nkx2-2 and upstream of Pet1, coupling early specification with terminal differentiation. Ectopic Lmx1b + Pet-1 expression induces 5-HT cells in ventral spinal cord; combined Lmx1b + Pet-1 + Nkx2.2 drives 5-HT differentiation in dorsal spinal cord. Lmx1b knockout mice; gain-of-function ectopic expression; genetic epistasis experiments Nature neuroscience / The Journal of neuroscience High 12897786 14602809
2004 Lmx1b controls the differentiation and migration of superficial dorsal horn neurons, regulates expression of downstream transcription factors Rnx and Drg11, maintains Ebf gene expression, and represses Zic genes; Lmx1b mutants also show disruption of cutaneous afferent ingrowth. Lmx1b knockout mouse analysis; in situ hybridization; immunohistochemistry Development (Cambridge, England) High 15229182
2006 Conditional deletion of Lmx1b specifically in Pet1-expressing 5-HT neurons shows Lmx1b is required for maintenance of differentiated serotonergic neurons postnatally: loss of Lmx1b leads to downregulation of Tph2 and Sert (most sensitive targets), loss of Pet1 expression, and eventual death of almost all central 5-HT neurons. Conditional (Cre-lox) knockout mouse; immunohistochemistry; gene expression analysis The Journal of neuroscience High 17151281
2006 Lmx1b is essential for expression of Fgf8, Wnt1, En1, and Pax2 at the midbrain-hindbrain boundary (MHB); Lmx1b-/- embryos lack Fgf8 expression at the 4-somite stage, with Wnt1 downregulated earlier, causing severe impairment of tectum and cerebellum development. Lmx1b knockout and conditional knockout mice; in situ hybridization; temporal expression analysis Development (Cambridge, England) High 17166916
2007 LMX1B directly regulates transcription of NF-κB target genes (IL-6, IL-8): ChIP demonstrates LMX1B binds the proximal promoters of IL-6 and IL-8 near the κB site; LMX1B-mediated transcription requires the κB site and an adjacent putative LMX1B binding motif; NF-κB activity is required for full induction. Tetracycline-inducible LMX1B expression system; microarray; ChIP; promoter-reporter assays; siRNA knockdown; Lmx1b-/- kidney expression analysis Experimental cell research High 18996370
2008 LMX1B is part of a transcriptional complex with PSPC1 and PSF in dopaminergic cells; affinity purification/MS identified PSPC1 as a binding partner, confirmed by co-immunoprecipitation in vitro and in vivo. Affinity purification + mass spectrometry; co-immunoprecipitation (reciprocal) in MN9D dopaminergic cells and in vivo PloS one Medium 23308148
2005 Lmx1b and Wnt1 are placed in a genetic hierarchy at the isthmus: Lmx1b misexpression in chick causes expansion of tectum and cerebellum, induces Wnt1 expression, and Wnt1 in turn induces Fgf8; Wnt1 cannot induce Lmx1b, placing Lmx1b upstream of Wnt1 in the cascade. Misexpression experiments in chick; in situ hybridization; genetic hierarchy analysis Development (Cambridge, England) Medium 12399317
2009 Foxa1 and Foxa2 positively regulate Lmx1b expression in mesodiencephalic dopaminergic progenitors; Foxa1/2 and Lmx1a/b subsequently cooperate to regulate mDA neuron differentiation; ChIP shows Nkx2.2 and TH are likely direct Foxa1/2 targets in mDA cells in vivo. Conditional knockout mice; ChIP; in situ hybridization Developmental biology Medium 19607821
2011 Lmx1a and Lmx1b function cooperatively to regulate proliferation and neuronal commitment of mDA progenitors through expression of Wnt1 and Ngn2; they negatively regulate Hes1 and promote p27Kip1-mediated cell cycle exit; they also regulate floor plate genes Corin and Slit2. Double conditional knockout (Lmx1a/Lmx1b) mice with ShhCre; gene expression analysis; neuronal counting The Journal of neuroscience High 21880902
2011 Lmx1b specifically regulates lateral mDA progenitors that do not originate from the floor plate; additionally, Lmx1b regulates Phox2a expression and the sequential specification of ocular motor neurons and red nucleus neurons in the midbrain. Conditional Lmx1b knockout mice; in situ hybridization; immunohistochemistry Development (Cambridge, England) Medium 21752929
2011 Adult raphe-specific inducible deletion of Lmx1b reduces brain 5-HT levels to ~60% of controls and greatly downregulates Tph2, Sert and Vmat2 expression, demonstrating Lmx1b is required for 5-HT biosynthesis and gene maintenance in adult serotonergic neurons. Inducible Cre-lox conditional KO (Pet1-CreERT2); tamoxifen induction; HPLC measurement of 5-HT; gene expression analysis PloS one High 21246047
2013 Inducible podocyte-specific Lmx1b knockout in adult mice causes proteinuria with actin cytoskeleton dysregulation; LMX1B binds AT-rich FLAT elements in promoters of ABRA and ARL4C by ChIP (human podocytes) and gel shift assays, identifying these as direct LMX1B targets in podocytes. Inducible podocyte-specific Cre-lox KO; ChIP; EMSA; DNA microarray; zebrafish morpholino knockdown Journal of the American Society of Nephrology High 23990680
2013 LMX1B forms an autoregulatory negative feedback loop with miR135a2 to modulate Wnt1/Wnt signaling: Lmx1b promotes Wnt1/Wnt signaling and miR135a2 expression, while miR135a2 targets Lmx1b and Wnt pathway genes; luciferase assay confirmed miR135a2 targets Lmx1b directly. Conditional gain/loss-of-function mouse models; luciferase reporter assay; bioinformatics; conditional Dicer1 deletion PLoS genetics Medium 24348261
2014 A dominant-negative Lmx1b mutation (V265D) that abolishes DNA binding causes glaucoma and semi-lethality in heterozygous mice via LDB1-mediated dimerization: co-IP shows both wild-type and mutant LMX1B form complexes with LDB1, reducing effective functional LMX1B in heterozygotes. ENU-induced mouse mutant; co-immunoprecipitation; transgenic rescue experiments PLoS genetics High 24809698
2014 LMX1B and FoxC2 combinatorially regulate podocin expression: a 49-bp enhancer containing adjacent FLAT-E and forkhead binding sites is bound by LMX1B and FoxC; double knockdown of both in zebrafish disrupts podocyte development synergistically, and co-overexpression potently induces nphs2. Zebrafish Tol2-mediated transgenesis; morpholino double knockdown; co-overexpression; EMSA; genome-wide motif search Journal of the American Society of Nephrology High 24854274
2015 Conditional ablation of Lmx1a and Lmx1b in adult mDA neurons leads to autophagic-lysosomal pathway impairment, α-synuclein(+) inclusions, and progressive dopaminergic neuron loss; Lmx1b is required for normal execution of autophagy in mDA neurons. Conditional knockout mice; autophagy pathway analysis; immunohistochemistry; neuronal counting; gene expression analysis Nature neuroscience High 25915474
2016 Conditional Lmx1a and Lmx1b inactivation in adult mDA neurons impairs respiratory chain activity, increases oxidative stress, and causes mitochondrial DNA damage, revealing Lmx1a/b control key mitochondrial function genes in adult dopaminergic neurons. Conditional double knockout mice; mitochondrial respiration assay; ROS measurement; mitochondrial DNA damage assay; gene expression analysis Proceedings of the National Academy of Sciences High 27407143
2017 Lmx1a and Lmx1b transcriptionally repress Plxnc1 (an axon guidance receptor), while Otx2 enhances it; Sema7a/Plxnc1 interactions mediated by Lmx1a/b repression are responsible for segregation of nigrostriatal and mesolimbic dopaminergic pathways. Conditional knockout mice; gene expression analysis; ChIP-seq (for Lmx1b binding); axonal projection analysis Nature communications Medium 29038581
2017 Genome-wide ChIP-seq in mouse limbs at E12.5 identified ~617 Lmx1b-bound genomic intervals; 84% overlap chromatin regulatory marks of active CRMs; Lmx1b directly binds a CRM associated with Gdf5 (joint-related gene) and a CRM associated with Lmx1b itself (autoregulation). ChIP-seq in mouse embryonic limbs; in vivo CRM validation; gene expression analysis Development (Cambridge, England) High 28455377
2018 Lmx1b functions as an anti-osteogenic transcription factor in early migrating mesenchyme (EMM) of the calvaria: head mesenchyme-specific deletion causes heterotopic ossification at the vertex and craniosynostosis; forced expression of Lmx1b in osteogenic mesenchyme inhibits osteogenic specification. Conditional head mesenchyme-specific KO; gain-of-function transgenic mice; calvarial phenotype analysis Developmental biology High 29852132
2019 Lmx1b is required at successive stages for 5-HT axon primary outgrowth, selective routing, and terminal arborization; a Lmx1b→Pet1 regulatory cascade temporally controls 5-HT arborization and upregulates Protocadherin-αc2 during postnatal forebrain 5-HT axon development. Stage-specific conditional targeting of Lmx1b; axonal projection analysis; gene expression analysis in serotonergic neurons eLife High 31355748
2021 Two conserved Lmx1b-associated cis-regulatory modules (LARM1 and LARM2) in the limb are directly bound by Lmx1b (ChIP), amplify Lmx1b expression in the limb, and are necessary for Lmx1b-mediated limb dorsalization; NPS patients carry loss-of-function variants in LARM1/2 without LMX1B coding mutations. ChIP; CRISPR/functional KO of LARM1/2; in vivo enhancer reporter assays; patient variant identification Nature communications High 34545091
2022 Lmx1b physically interacts with and represses the transcriptional activity of Runx2 by reducing Runx2 recruitment to its target gene promoters, thereby negatively regulating BMP2-induced osteoblast differentiation. Co-immunoprecipitation; ChIP; overexpression and knockdown in osteoblast precursors; in vivo BMP2-induced ectopic bone formation assay International journal of molecular sciences Medium 35563615
2023 LMX1B stability is regulated by autophagy; LMX1B binds multiple ATG8/LC3 proteins in a nutrient-status- and localization-dependent manner (nuclear under basal conditions, cytosolic+nuclear during starvation); ATG8 binding stimulates LMX1B-mediated transcription for efficient autophagy and stress protection in mDA neurons. iPSC-derived mDA neurons; co-IP of LMX1B with ATG8 proteins; subcellular fractionation; overexpression/knockdown; rotenone toxicity assay; mitochondrial respiration analysis The Journal of cell biology High 37014324
2003 LMX1B interacts with PAX2 protein as demonstrated by yeast two-hybrid assay and co-immunoprecipitation. Yeast two-hybrid; co-immunoprecipitation European journal of human genetics Low 15785774
2003 CLIM2/LDB1 interaction with LMX1B confirmed by yeast two-hybrid screening, consistent with prior biochemical reports. Yeast two-hybrid International journal of molecular medicine Low 12792813
2008 In Xenopus, lmx1b morpholino knockdown causes reduced glomus size and reduced/absent pronephric tubule coiling; co-injection experiments show lmx1b overexpression with Lim1 and Ldb1 partially rescues Lim1/Ldb1 phenotypes, and animal cap assays show co-injection upregulates pronephric markers, placing lmx1b upstream of wt1 in glomus differentiation. Morpholino knockdown in Xenopus; mRNA overexpression; animal cap assay; in situ hybridization Developmental biology Medium 18687324
2010 In Xenopus, spontaneous calcium spike activity in the hindbrain regulates serotonergic neuron specification via regulation of Lmx1b expression; activity acts downstream of Nkx2.2 but upstream of Lmx1b in the 5-HT specification cascade. Calcium imaging; targeted Lmx1b expression manipulation; cell counting in Xenopus laevis larvae Neuron Medium 20670838
2010 Lmx1b activity is required cell-autonomously in skeletal progenitors to direct dorsal pattern, but loss or gain of Lmx1b in skeletal progenitors (via Sox9-Cre) has no effect on muscle or connective tissue patterning, demonstrating that skeletal and connective tissue patterning can be uncoupled. Conditional gain- and loss-of-function with Sox9-Cre in mice; limb skeletal and muscle phenotype analysis Development (Cambridge, England) High 20215352

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nature genetics 402 9590288
1998 Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nature genetics 364 9590287
2000 A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nature neuroscience 316 10725922
2003 Lmx1b is essential for the development of serotonergic neurons. Nature neuroscience 213 12897786
2006 Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 170 17151281
1998 Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome. Human molecular genetics 165 9618165
2001 Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nature genetics 142 11175791
2003 Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype. The Journal of neuroscience : the official journal of the Society for Neuroscience 140 14602809
1998 Mutation analysis of LMX1B gene in nail-patella syndrome patients. American journal of human genetics 128 9837817
2000 LMX1B, a LIM homeodomain class transcription factor, is necessary for normal development of multiple tissues in the anterior segment of the murine eye. Genesis (New York, N.Y. : 2000) 124 10660670
2011 Lmx1a and lmx1b function cooperatively to regulate proliferation, specification, and differentiation of midbrain dopaminergic progenitors. The Journal of neuroscience : the official journal of the Society for Neuroscience 117 21880902
2009 Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Developmental biology 116 19607821
2002 Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. The Journal of clinical investigation 114 11956244
2005 Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. European journal of human genetics : EJHG 107 15928687
2011 Specific and integrated roles of Lmx1a, Lmx1b and Phox2a in ventral midbrain development. Development (Cambridge, England) 106 21752929
2002 The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. The Journal of clinical investigation 105 11956245
2000 The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer. Development (Cambridge, England) 101 10751174
2009 Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of dopaminergic neurons and control of floor plate cell differentiation in the developing mesencephalon. Developmental biology 96 20035737
2004 Lmx1b controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord. Development (Cambridge, England) 95 15229182
2002 Role of Lmx1b and Wnt1 in mesencephalon and metencephalon development. Development (Cambridge, England) 82 12399317
2006 Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development (Cambridge, England) 80 17166916
1998 A mutation in NPS1/STH1, an essential gene encoding a component of a novel chromatin-remodeling complex RSC, alters the chromatin structure of Saccharomyces cerevisiae centromeres. Nucleic acids research 79 9628931
2000 LMX1B transactivation and expression in nail-patella syndrome. Human molecular genetics 78 10767331
2016 Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons. Proceedings of the National Academy of Sciences of the United States of America 76 27407143
2007 Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and noradrenergic neuronal development. BMC developmental biology 74 18053265
2010 Activity-dependent expression of Lmx1b regulates specification of serotonergic neurons modulating swimming behavior. Neuron 73 20670838
2013 LMX1B mutations cause hereditary FSGS without extrarenal involvement. Journal of the American Society of Nephrology : JASN 72 23687361
1992 The Saccharomyces cerevisiae NPS1 gene, a novel CDC gene which encodes a 160 kDa nuclear protein involved in G2 phase control. The EMBO journal 72 1396591
2010 Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling influences the neurogenic and non-neurogenic domains in the chick otic placode. Developmental biology 70 20043898
2015 Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease. Nature neuroscience 66 25915474
2011 Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency. PloS one 63 21246047
2008 Postnatal ontogeny of the transcription factor Lmx1b in the mouse central nervous system. The Journal of comparative neurology 60 18512225
2015 Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b. FEBS letters 57 26526610
2009 Overlapping function of Lmx1a and Lmx1b in anterior hindbrain roof plate formation and cerebellar growth. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 19741143
2002 Interactions between dorsal-ventral patterning genes lmx1b, engrailed-1 and wnt-7a in the vertebrate limb. The International journal of developmental biology 55 12455631
2002 CNS expression pattern of Lmx1b and coexpression with ptx genes suggest functional cooperativity in the development of forebrain motor control systems. Molecular and cellular neurosciences 54 12498783
2013 An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool. PLoS genetics 53 24348261
2013 LMX1B is essential for the maintenance of differentiated podocytes in adult kidneys. Journal of the American Society of Nephrology : JASN 52 23990680
2007 The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Developmental biology 48 17316599
2004 The human LMX1B gene: transcription unit, promoter, and pathogenic mutations. Genomics 46 15498463
2000 Nail-patella syndrome: identification of mutations in the LMX1B gene in Dutch families. Journal of the American Society of Nephrology : JASN 43 10966502
1998 Multiple calvarial defects in lmx1b mutant mice. Developmental genetics 43 9664684
2007 Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1 deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar syndrome. American journal of medical genetics. Part A 42 17431898
2020 Lmx1a and Lmx1b are Redundantly Required for the Development of Multiple Components of the Mammalian Auditory System. Neuroscience 41 33246067
2005 Functional characterization of LMX1B mutations associated with nail-patella syndrome. Pediatric research 40 15774843
2005 Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. Development (Cambridge, England) 40 15944182
1999 Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients. Human mutation 39 10571942
2003 In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys. The American journal of pathology 38 12819019
2015 Hoxb8 intersection defines a role for Lmx1b in excitatory dorsal horn neuron development, spinofugal connectivity, and nociception. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 25834049
2014 A dominant-negative mutation of mouse Lmx1b causes glaucoma and is semi-lethal via LDB1-mediated dimerization [corrected]. PLoS genetics 34 24809698
2008 Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man. European journal of human genetics : EJHG 34 18414507
2012 Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats. Neuroscience 33 22641087
2010 Uncoupling skeletal and connective tissue patterning: conditional deletion in cartilage progenitors reveals cell-autonomous requirements for Lmx1b in dorsal-ventral limb patterning. Development (Cambridge, England) 32 20215352
2019 Lmx1b is required at multiple stages to build expansive serotonergic axon architectures. eLife 31 31355748
2013 LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 31 24042019
2009 Manifold functions of the Nail-Patella Syndrome gene Lmx1b in vertebrate development. Development, growth & differentiation 31 19222527
2008 Identification of genes controlled by LMX1B in the developing mouse limb bud. Developmental dynamics : an official publication of the American Association of Anatomists 31 18351676
2014 Lmx1b and FoxC combinatorially regulate podocin expression in podocytes. Journal of the American Society of Nephrology : JASN 30 24854274
1999 Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome. International journal of molecular medicine 30 10425280
1986 Characterization of NPS-1, a novel plasmid-mediated beta-lactamase, from two Pseudomonas aeruginosa isolates. Antimicrobial agents and chemotherapy 28 3089139
2017 Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation. Nature communications 27 29038581
2021 Genetic background modifies vulnerability to glaucoma-related phenotypes in Lmx1b mutant mice. Disease models & mechanisms 26 33462143
2021 Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity. Nature communications 24 34545091
2014 A novel LMX1B mutation in a family with end-stage renal disease of 'unknown cause'. Clinical kidney journal 24 25713721
1999 Nps1/Sth1p, a component of an essential chromatin-remodeling complex of Saccharomyces cerevisiae, is required for the maximal expression of early meiotic genes. Genes to cells : devoted to molecular & cellular mechanisms 24 10320476
2004 Lmx1b expression during joint and tendon formation: localization and evaluation of potential downstream targets. Gene expression patterns : GEP 23 15183306
2001 Twenty-two novel LMX1B mutations identified in nail patella syndrome (NPS) patients. Human mutation 23 11668639
2010 A spectrum of LMX1B mutations in Nail-Patella syndrome: new point mutations, deletion, and evidence of mosaicism in unaffected parents. Genetics in medicine : official journal of the American College of Medical Genetics 22 20531206
2009 Lmx1b-expressing cells in the mouse limb bud define a dorsal mesenchymal lineage compartment. Genesis (New York, N.Y. : 2000) 22 19298015
2008 The LIM-homeodomain transcription factor LMX1B regulates expression of NF-kappa B target genes. Experimental cell research 22 18996370
2005 A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression. European journal of human genetics : EJHG 22 15562281
2017 Lmx1b-targeted cis-regulatory modules involved in limb dorsalization. Development (Cambridge, England) 21 28455377
2015 Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic Neurons. PloS one 21 26444681
2012 Detection of genes regulated by Lmx1b during limb dorsalization. Development, growth & differentiation 20 22417325
2012 The signaling pathways of LMX1B and its role in glomerulosclerosis. Journal of receptor and signal transduction research 20 23046462
2018 Anti-osteogenic function of a LIM-homeodomain transcription factor LMX1B is essential to early patterning of the calvaria. Developmental biology 19 29852132
2019 Deletion of the Nonribosomal Peptide Synthetase Gene nps1 in the Fungus Clonostachys rosea Attenuates Antagonism and Biocontrol of Plant Pathogenic Fusarium and Nematodes. Phytopathology 18 31120795
2013 LMX1B is part of a transcriptional complex with PSPC1 and PSF. PloS one 18 23308148
2013 Lmx-1b and Wnt-7a expression in axolotl limb during development and regeneration. Okajimas folia anatomica Japonica 18 23614984
2013 Identification of LMX1B as a novel oncogene in human ovarian cancer. Oncogene 18 24056967
2020 Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis. Pediatric nephrology (Berlin, Germany) 17 32356190
2016 Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons. Neural development 17 27553035
2011 c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail-patella syndrome associated with glaucoma. Molecular vision 17 21850167
2010 Increased symptoms of attention deficit hyperactivity disorder and major depressive disorder symptoms in Nail-patella syndrome: potential association with LMX1B loss-of-function. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 17 21184584
2008 The lmx1b gene is pivotal in glomus development in Xenopus laevis. Developmental biology 17 18687324
2005 Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in Nail-Patella syndrome. European journal of human genetics : EJHG 17 15785774
2004 Characterization of migration behavior of myogenic precursor cells in the limb bud with respect to Lmx1b expression. Anatomy and embryology 17 15007643
2003 Isolation and growth factor inducibility of the Xenopus laevis Lmx1b gene. The International journal of developmental biology 17 12755330
2023 ATG8-dependent LMX1B-autophagy crosstalk shapes human midbrain dopaminergic neuronal resilience. The Journal of cell biology 16 37014324
2010 The transcription factor, Lmx1b, is necessary for the development of the principal trigeminal nucleus-based lemniscal pathway. Molecular and cellular neurosciences 16 20621716
2003 Confirmation of CLIM2/LMX1B interaction by yeast two-hybrid screening and analysis of its involvement in nail-patella syndrome. International journal of molecular medicine 16 12792813
2022 Knockdown of LMX1B Suppressed Cell Apoptosis and Inflammatory Response in IL-1β-Induced Human Osteoarthritis Chondrocytes through NF-κB and NLRP3 Signal Pathway. Mediators of inflammation 14 36133743
2016 Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation. Nephrology (Carlton, Vic.) 14 26560070
2007 Novel LMX1B mutation in familial nail-patella syndrome with variable expression of open angle glaucoma. Molecular vision 14 17515884
2006 Genitopatellar syndrome: expanding the phenotype and excluding mutations in LMX1B and TBX4. American journal of medical genetics. Part A 14 16761293
2022 LMX1B Activated Circular RNA GFRA1 Modulates the Tumorigenic Properties and Immune Escape of Prostate Cancer. Journal of immunology research 13 35832649
2015 9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping. European journal of human genetics : EJHG 13 26395556
2017 LMX1B-Associated Nephropathy With Type III Collagen Deposition in the Glomerular and Tubular Basement Membranes. American journal of kidney diseases : the official journal of the National Kidney Foundation 12 29246420
2000 Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome. European journal of human genetics : EJHG 12 10854116
2022 Transcription Factor Lmx1b Negatively Regulates Osteoblast Differentiation and Bone Formation. International journal of molecular sciences 11 35563615

Missed literature

Know a paper Affinage missed for LMX1B? Flag it for the maintainers and the community.

No submissions yet.