Affinage

HESX1

Homeobox expressed in ES cells 1 · UniProt Q9UBX0

Length
185 aa
Mass
21.4 kDa
Annotated
2026-04-28
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HESX1 is a paired-like homeodomain transcriptional repressor essential for anterior forebrain, midline, and pituitary development during early embryogenesis. It acts cell-autonomously in the anterior neural ectoderm, where it suppresses Wnt/β-catenin signalling and represses homeodomain activators such as PROP1 by recruiting TLE1/TLE3 (Groucho family) corepressors through its N-terminal engrailed homology 1 (eh1) domain and binding target DNA via its homeodomain (Kd ~31 nM), with DNMT1 also recruited as an additional corepressor partner (PMID:11748154, PMID:14561704, PMID:20181723, PMID:17931718, PMID:17360769). Knock-in studies show that disruption of DNA binding (R160C) phenocopies the null, whereas disruption of TLE recruitment alone (I26T) produces a hypomorphic phenotype with pituitary defects but a normal telencephalon, demonstrating separable domain contributions to forebrain versus pituitary specification (PMID:19093031). Loss-of-function mutations cause septo-optic dysplasia and combined pituitary hormone deficiency, while a gain-of-repressor-function frameshift mutation reveals that excessive HESX1-mediated repression of PROP1 is also pathogenic (PMID:9620767, PMID:14557462).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Establishing that Hesx1 (Rpx) encodes a novel 185-amino-acid homeodomain protein expressed exclusively in early embryonic tissues defined the gene as a developmental transcription factor.

    Evidence Molecular cloning, Northern blot, and sequence analysis from embryonic stem cells

    PMID:7876132

    Open questions at the time
    • No functional assay performed
    • Target genes and binding sites unknown
    • Protein-protein interactions uncharacterized
  2. 1996 High

    Epistasis analysis placed Hesx1 downstream of the Ames dwarf (Prop1) locus and showed that persistent Hesx1 expression blocks pituitary lineage-specific proliferation, establishing Hesx1 downregulation as a prerequisite for pituitary differentiation.

    Evidence Double-mutant epistasis in df and Pit1dw mice with in situ hybridisation and cell proliferation assays

    PMID:8961267

    Open questions at the time
    • Direct transcriptional relationship between PROP1 and HESX1 not tested
    • Mechanism of Hesx1 downregulation unknown
  3. 1998 High

    Demonstrating that Hesx1-null mice have forebrain, midline, and pituitary defects and that a patient R53C homeodomain mutation abolishes DNA binding established HESX1 as a disease gene for septo-optic dysplasia and linked its function to homeodomain-mediated DNA binding.

    Evidence Knockout mouse phenotyping, human mutation screening, gel-shift DNA binding assay

    PMID:9620767

    Open questions at the time
    • Transcriptional targets not identified
    • Repression mechanism unknown
    • Heterozygous vs homozygous genotype-phenotype correlation incomplete
  4. 2000 High

    Chimera analysis resolved the tissue requirement, showing Hesx1 is needed cell-autonomously in the anterior neural ectoderm (not visceral endoderm) and its absence leads to loss of Six3 and Rax expression, placing it upstream of these forebrain determinants.

    Evidence ES-cell chimeric embryo analysis with RNA in situ hybridisation

    PMID:10882526

    Open questions at the time
    • Whether Hesx1 directly regulates Six3/Rax transcription or acts indirectly not determined
    • Downstream signalling pathways not identified
  5. 2001 High

    Quantitative biochemistry and reporter assays showed HESX1 is a promoter-specific transcriptional repressor that opposes homeodomain activators, with a minimal 36-amino-acid repression domain, and revealed that R160C acts as a dominant negative by sequestering wild-type protein through this domain.

    Evidence EMSA with Kd measurements, deletion mutagenesis, cell-based reporter assays, dominant-negative transfection experiments

    PMID:11136712 PMID:11748154

    Open questions at the time
    • Identity of the endogenous corepressor recruited by the repression domain not yet known
    • Direct genomic targets not identified
  6. 2003 High

    Identification that the I26T eh1-domain mutation disrupts TLE1 corepressor recruitment without affecting DNA binding, while a gain-of-function frameshift increases DNA binding and repression, established two distinct disease mechanisms — loss of corepressor recruitment and gain of repressor function.

    Evidence Corepressor recruitment assays, DNA binding assays, PROP1-dependent reporter assays, patient mutation analysis

    PMID:14557462 PMID:14561704

    Open questions at the time
    • Whether TLE1 is the sole corepressor mediating HESX1 repression in vivo unknown
    • Structural basis of eh1-TLE interaction not resolved
  7. 2004 Medium

    Upstream regulation was defined: Otx2 directly activates Hesx1 through conserved promoter sites, while Pax6 represses it, explaining how Hesx1 expression is restricted to the anterior forebrain domain.

    Evidence Transgenic reporter analysis, in vivo electroporation in chick, Pax6 knockout mouse in situ hybridisation, binding assays

    PMID:15110720

    Open questions at the time
    • Whether Otx2 and Pax6 are sufficient to account for all spatial regulation not tested
    • Chromatin context of regulation not examined
  8. 2006 Medium

    Identification of Lhx1/Lhx3 binding sites in the 5' upstream region and separate 3' elements for Rathke's pouch expression resolved the modular regulatory architecture of the Hesx1 locus across developmental stages.

    Evidence Transgenic mouse reporter deletion analysis and EMSA for LIM protein binding, cross-species validation

    PMID:16527264

    Open questions at the time
    • In vivo occupancy by Lhx1/Lhx3 not confirmed by ChIP
    • How 3' regulatory elements integrate with 5' elements during the transition from neural plate to Rathke's pouch unclear
  9. 2007 High

    Discovery that HESX1 represses Wnt/β-catenin signalling cell-autonomously in the anterior forebrain, with conditional rescue reversing anterior-to-posterior transformation, placed HESX1 squarely within the Wnt antagonism pathway during forebrain patterning.

    Evidence Conditional transgenic rescue in Hesx1-null mice, genetic cell labelling, in situ hybridisation for Wnt targets

    PMID:17360769

    Open questions at the time
    • Direct Wnt pathway target genes repressed by HESX1 not identified
    • Whether HESX1 represses Wnt ligands, receptors, or intracellular components unclear
  10. 2007 Medium

    Identification of DNMT1 as a HESX1-interacting protein suggested an epigenetic repression mechanism involving DNA methylation, adding a second corepressor axis beyond TLE.

    Evidence Yeast two-hybrid screen, deletion mapping, co-immunoprecipitation, immunofluorescence co-localisation

    PMID:17931718

    Open questions at the time
    • Functional consequence of HESX1-DNMT1 interaction on target gene methylation not demonstrated
    • Interaction not validated at endogenous expression levels
    • Relevance in vivo not tested
  11. 2008 High

    Knock-in of I26T (eh1) and R160C (homeodomain) mutations in mice dissected domain contributions in vivo: the homeodomain null phenocopies the full knockout (forebrain + pituitary defects), while the eh1 hypomorph selectively disrupts pituitary development, demonstrating that corepressor recruitment is specifically critical for pituitary but dispensable for telencephalon specification.

    Evidence Two independent knock-in mouse models with histological and developmental phenotyping compared to null allele

    PMID:19093031

    Open questions at the time
    • Why the eh1 domain is dispensable for forebrain function not mechanistically explained
    • Alternative corepressor recruitment in the forebrain not investigated
  12. 2008 High

    Genetic interaction between Hesx1 and Six3 was demonstrated by compound heterozygotes exhibiting severe pituitary hypoplasia, establishing a cooperative epistatic network between these homeobox genes in anterior pituitary organogenesis.

    Evidence Compound heterozygous Six3+/-;Hesx1Cre/+ mice with histology, proliferation, and endocrine phenotyping

    PMID:18775421

    Open questions at the time
    • Whether HESX1 and Six3 regulate shared target genes or act in parallel unknown
    • Biochemical interaction between HESX1 and SIX3 proteins not tested
  13. 2010 High

    Expanded characterisation showed HESX1 represses PROP1-mediated transcription through both TLE1 and TLE3, and that persistent HESX1 expression in transgenic pituitary suppresses terminal differentiation of thyrotrophs and gonadotrophs, confirming the in vivo repressor role against PROP1-driven differentiation.

    Evidence Co-immunoprecipitation, cell-based reporter assay, transgenic mouse pituitary overexpression with cell-type differentiation phenotyping

    PMID:20181723

    Open questions at the time
    • Direct genomic binding sites of the HESX1-TLE complex on PROP1 targets not mapped
    • Whether TLE1 and TLE3 are redundant or have distinct roles in pituitary cell fate not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct genomic targets of HESX1 remain unidentified genome-wide; the structural basis for its interactions with TLE corepressors and DNMT1 is unresolved; and the mechanism by which it selectively antagonises Wnt/β-catenin signalling in the anterior forebrain has not been molecularly defined.
  • No ChIP-seq or equivalent genome-wide binding data
  • No structural model of HESX1 or its corepressor complexes
  • Wnt target gene specificity of HESX1-mediated repression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 1
Partners
DNMT1PROP1SIX3TLE1TLE3ZYX

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 HESX1 encodes a homeodomain transcription factor required for forebrain, midline, and pituitary development; the Arg53Cys missense mutation within the homeodomain destroys its ability to bind target DNA in vitro. Homozygous knock-out mouse, human mutation screening, in vitro DNA binding assay (gel shift) Nature genetics High 9620767
1995 Hesx1 (Rpx) is expressed as two transcripts encoding an identical 185-amino-acid homeodomain protein; its homeodomain shares 80% identity with Xenopus XANF-1, defining a new homeodomain class; expression is restricted to early embryonic tissues and is absent in adult mice. Molecular cloning, Northern blot, sequence analysis of transcripts from embryonic stem cells The Journal of biological chemistry High 7876132
2001 HESX1 is a promoter-specific transcriptional repressor with a minimal 36-amino-acid repression domain that suppresses homeodomain-containing activator proteins; disease-associated mutations (R160C, S170L) reduce DNA-binding affinity (wild-type Kd 31 nM; S170L Kd 150 nM; R160C no binding), and R160C acts as a dominant negative by inhibiting wild-type HESX1 DNA binding both in vitro and in cell culture via the repression domain. Promoter-specific reporter assays, EMSA/gel shift with quantitative Kd measurement, dominant-negative cell culture transfection, deletion mutagenesis of repression domain Development (Cambridge, England) High 11748154
2001 Heterozygous HESX1 missense mutation S170L significantly reduces relative DNA-binding activity compared with wild-type HESX1, as demonstrated by gel shift analysis. Gel shift (EMSA) assay of mutant HESX1-S170L protein Human molecular genetics Medium 11136712
2003 A homozygous I26T mutation in the Engrailed homology 1 (eh1) repressor domain of HESX1 does not affect DNA binding but impairs recruitment of the Groucho/TLE1 corepressor, leading to partial loss of transcriptional repression; this establishes the eh1 domain as the interface for TLE corepressor interaction. In vitro DNA binding assay, corepressor recruitment assay, reporter gene repression assay in cell culture, patient mutation analysis The Journal of clinical investigation High 14561704
2003 A frameshift deletion mutation (g.1684delG) in HESX1 produces a mutant protein with increased DNA binding, causing enhanced repression of PROP1-dependent gene activity, revealing that gain-of-repressor-function is a novel disease mechanism. Reporter gene assay measuring PROP1-mediated transcriptional activation in the presence of mutant HESX1 The Journal of clinical endocrinology and metabolism Medium 14557462
2010 HESX1 interacts with both TLE1 and TLE3 corepressors through its engrailed homology domain to repress PROP1-mediated transcription; TLE1 and TLE3 can also repress PROP1 independently of HESX1 via protein-protein interaction, and ectopic HESX1 expression in transgenic mouse pituitary suppresses terminal differentiation of thyrotrophs and gonadotrophs. Cell-based reporter assay, co-immunoprecipitation, transgenic mouse overexpression with cell-type differentiation phenotyping Molecular endocrinology (Baltimore, Md.) High 20181723
2007 DNMT1 (DNA methyltransferase 1) is a HESX1-binding protein identified by yeast two-hybrid screen; interaction requires the entire HESX1 protein and a portion of the DNMT1 N-terminus plus its C-terminal catalytic domain; HESX1-DNMT1 complexes co-immunoprecipitate from cells and co-localise in the nucleus, suggesting DNMT1 recruitment as a mechanism for HESX1-mediated transcriptional repression. Yeast two-hybrid screen, deletion mapping, co-immunoprecipitation, co-localisation by immunofluorescence Biochimica et biophysica acta Medium 17931718
2007 Absence of Hesx1 leads to ectopic activation of Wnt/β-catenin signalling within the anterior forebrain expression domain of Hesx1, causing posterior transformation of the anterior forebrain; conditional re-expression of Hesx1 within the anterior forebrain rescues the forebrain defect, establishing that Hesx1 represses Wnt/β-catenin signalling cell-autonomously in the anterior neural plate. Genetic cell labelling, marker analysis, epistasis via conditional transgenic rescue, in situ hybridisation for Wnt target genes in Hesx1-/- mice Development (Cambridge, England) High 17360769
2000 Hesx1 is required cell-autonomously in the anterior neural ectoderm (ANE) for normal forebrain formation; chimera analysis shows that Hesx1-/- visceral endoderm does not cause forebrain defects, but Hesx1-/- cells in the ANE do; absence of Hesx1 in ANE leads to downregulation of Six3 and Rax/Rx by the early somite stage. Chimeric embryo analysis (ES cell injection into blastocysts), RNA in situ hybridisation for forebrain markers Developmental biology High 10882526
2008 Hesx1 and Six3 interact genetically in pituitary development: compound heterozygous Six3+/-;Hesx1Cre/+ mice display severe dwarfism and pituitary hypoplasia with expanded and bifurcated Rathke's pouch, phenocopying Hesx1-null defects, revealing a cooperative epistatic relationship between these two homeobox genes in anterior pituitary organogenesis. Double-heterozygous compound mutant mouse analysis, histology, cell proliferation assays, endocrine phenotyping Developmental biology High 18775421
2008 The Xanf1/Hesx1 homeodomain repressor binds the LIM-domain protein Zyxin; the eh1 (Engrailed-type) repressor domain of Xanf1 and LIM2-domain of Zyxin are primarily responsible for the interaction; Zyxin overexpression phenocopies Xanf1 loss-of-function, while repressor-fused Zyxin mimics Xanf1 overexpression, indicating Zyxin acts as a negative modulator of Xanf1 transcriptional repressing activity in the anterior neural plate. Co-immunoprecipitation, deletion mutant mapping, Xenopus overexpression/loss-of-function embryo assay Developmental dynamics Medium 18297730
2004 The transcription factor Otx2 binds conserved sites in the ANF/Hesx1 promoter and is required for its activation in the anterior embryonic region; Pax6 binds a site near the transcriptional start site and inhibits Hesx1 expression (Pax6-/- mice show expanded Hesx1 domain); these factors are key regulators of forebrain-specific Hesx1 gene expression. Transgenic reporter analysis, in vivo electroporation in chick, Pax6 knockout mouse in situ hybridisation, gel shift/in vivo ChIP-like binding assays Developmental biology Medium 15110720
2006 Regulatory sequences in the 5' upstream region of Rpx/Hesx1 control early expression in anterior endoderm/neural plate, while 3' regulatory elements are required for late expression in Rathke's pouch; the LIM homeodomain proteins Lim1/Lhx1 and Lhx3 directly bind two LIM protein-binding sites in the 5' upstream region, which are required for Rpx promoter activity in both mice and Xenopus. Transgenic mouse reporter assay with deletion analysis, EMSA for LIM protein binding to promoter sites, cross-species conservation analysis Developmental biology Medium 16527264
2008 Knock-in of the I26T mutation (in the eh1 repressor domain) produces a hypomorphic allele with pituitary defects comparable to Hesx1-null but normal telencephalon, while knock-in of R160C (homeodomain) produces a null allele with forebrain and pituitary defects identical to Hesx1-null mice, demonstrating that eh1 and homeodomain mutations have distinct phenotypic consequences consistent with their distinct molecular defects (corepressor recruitment vs. DNA binding). Knock-in mouse models, histological and developmental phenotyping, comparison with null allele Disease models & mechanisms High 19093031
1996 In Ames dwarf (df) mutant mice, Rpx (Hesx1) expression is not extinguished in the pituitary on embryonic day 13.5, while in Snell dwarf (Pit1dw) mutants Rpx is appropriately downregulated; double-mutant epistasis shows df acts upstream of Pit1 in the pituitary differentiation cascade, placing Hesx1 downregulation as a prerequisite for lineage-specific cell proliferation. Genetic epistasis with double-mutant analysis, in situ hybridisation for Rpx expression, cell proliferation assays Molecular endocrinology (Baltimore, Md.) High 8961267
2006 Two novel homozygous HESX1 mutations (frameshift c.449_450delAC and splice defect c.357+2T>C) produce truncated proteins lacking most or all of the homeodomain that are unable to repress PROP1 activity in a transcriptional reporter assay, confirming that HESX1 repressor function requires an intact homeodomain. Patient mutation sequencing, transcript analysis, transcriptional repression reporter assay The Journal of clinical endocrinology and metabolism Medium 16940453

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nature genetics 511 9620767
2002 Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Genes & development 292 12023302
1996 Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo. Development (Cambridge, England) 245 8565852
2001 Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Human molecular genetics 208 11136712
1986 Myocardial recruitment during ANF mRNA increase with volume overload in the rat. The American journal of physiology 204 2430471
1985 Localization of immunoreactive synthetic atrial natriuretic factor (ANF) in the heart of various animal species. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 191 3158698
1996 The Ames dwarf gene, df, is required early in pituitary ontogeny for the extinction of Rpx transcription and initiation of lineage-specific cell proliferation. Molecular endocrinology (Baltimore, Md.) 138 8961267
2001 Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders. Development (Cambridge, England) 104 11748154
2006 HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. The Journal of clinical endocrinology and metabolism 103 17148560
1985 Dopamine receptor antagonists inhibit the natriuretic response to atrial natriuretic factor (ANF). Life sciences 103 3158789
2003 A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. The Journal of clinical investigation 102 14561704
1995 Sequence, genomic organization, and expression of the novel homeobox gene Hesx1. The Journal of biological chemistry 93 7876132
1991 Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity. The Journal of antibiotics 93 1849131
2000 The homeobox gene Hesx1 is required in the anterior neural ectoderm for normal forebrain formation. Developmental biology 91 10882526
1995 Divergent pathways mediate the induction of ANF transgenes in neonatal and hypertrophic ventricular myocardium. The Journal of clinical investigation 84 7657806
1992 Neurohormonal inhibition and hemodynamic unloading during prolonged inhibition of ANF degradation in patients with severe chronic heart failure. Circulation 79 1394917
1989 UK-69,578, a novel inhibitor of EC 3.4.24.11 which increases endogenous ANF levels and is natriuretic and diuretic. Biochemical and biophysical research communications 78 2529858
1985 Structure-activity relationships of atrial natriuretic factor (ANF). II. Effect of chain-length modifications on vascular reactivity. Biochemical and biophysical research communications 78 4038600
2007 Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. Development (Cambridge, England) 68 17360769
1994 Classical, novel and atypical isoforms of PKC stimulate ANF- and TRE/AP-1-regulated-promoter activity in ventricular cardiomyocytes. FEBS letters 68 7805853
1991 Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments. The Journal of antibiotics 67 1826288
2005 Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia. Clinical endocrinology 63 15670191
1991 Kidney function in ANF-transgenic mice: effect of blood volume expansion. The American journal of physiology 62 1825155
2003 Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. The Journal of clinical endocrinology and metabolism 61 14557462
1989 Mammalian cAMP-responsive element can activate transcription in yeast and binds a yeast factor(s) that resembles the mammalian transcription factor ANF. Proceedings of the National Academy of Sciences of the United States of America 61 2538834
1991 The presence of atrial-natriuretic-factor receptors of ANF-R2 subtype in rat platelets. Coupling to adenylate cyclase/cyclic AMP signal-transduction system. The Biochemical journal 59 1652938
1988 Glomerular ANF receptor regulation during changes in sodium and water metabolism. The American journal of physiology 59 2827518
2006 Novel HESX1 mutations associated with a life-threatening neonatal phenotype, pituitary aplasia, but normally located posterior pituitary and no optic nerve abnormalities. The Journal of clinical endocrinology and metabolism 58 16940453
1986 Dopaminergic mediation of the diuretic and natriuretic effects of ANF in the rat. Life sciences 58 2941632
2008 Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Developmental biology 51 18775421
2001 Regulation of the ANF and BNP promoters by GATA factors: lessons learned for cardiac transcription. Canadian journal of physiology and pharmacology 51 11558676
1990 Degradation and clearance of atrial natriuretic factors (ANF). Life sciences 50 2173807
1989 Urodilatin and beta-ANF: binding properties and activation of particulate guanylate cyclase. Biochemical and biophysical research communications 50 2570574
2000 The Rho effector, PKN, regulates ANF gene transcription in cardiomyocytes through a serum response element. American journal of physiology. Heart and circulatory physiology 49 10843871
1976 Cooperative control of translational fidelity by ribosomal proteins in Escherichia coli. III. A ram mutation in the structural gene for protein S5 (rpx E). Molecular & general genetics : MGG 48 772415
1993 Characterization of anf genes specific for the alternative nitrogenase and identification of nif genes required for both nitrogenases in Rhodobacter capsulatus. Molecular microbiology 47 8332060
1986 Localization and characterization of atrial natriuretic factor (ANF)-like peptide in the frog atrium. Peptides 46 2945164
1985 Structure-activity relationships of atrial natriuretic factor (ANF). III. Correlation of receptor affinity with relative potency on aldosterone production in zona glomerulosa cells. Biochemical and biophysical research communications 45 2998358
1991 RT-PCR microlocalization of mRNA for guanylyl cyclase-coupled ANF receptor in rat kidney. The American journal of physiology 43 1721496
2004 Involvement of Pax6 and Otx2 in the forebrain-specific regulation of the vertebrate homeobox gene ANF/Hesx1. Developmental biology 42 15110720
1993 Differential antimitogenic effectiveness of atrial natriuretic peptides in primary versus subcultured rat aortic smooth muscle cells: relationship to expression of ANF-C receptors. Journal of cellular physiology 40 7678266
1995 Atrial natriuretic factor modulates nitric oxide production: an ANF-C receptor-mediated effect. Journal of hypertension 39 7594419
1992 Captopril enhances renal responsiveness to ANF in dogs with compensated high-output heart failure. The American journal of physiology 39 1313653
1988 ANF receptors: distribution and regulation in central and peripheral tissues. Neuroscience and biobehavioral reviews 39 2845313
1995 Heterogeneity within human-derived centers for disease control and prevention (CDC) coryneform group ANF-1-like bacteria and description of Corynebacterium auris sp. nov. International journal of systematic bacteriology 37 7547292
2008 Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism. Disease models & mechanisms 35 19093031
2007 Hormonal, pituitary magnetic resonance, LHX4 and HESX1 evaluation in patients with hypopituitarism and ectopic posterior pituitary lobe. Clinical endocrinology 34 17201807
2003 Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging. Hormone research 34 14646405
1993 Taxonomic study of Corynebacterium Group ANF-1 strains: Proposal of Corynebacterium afermentans sp. nov. containing the subspecies C. afermentans subsp. afermentans subsp. nov. and C. afermentans subsp. lipophilum subsp. nov. International journal of systematic bacteriology 34 8494739
2000 Dopamine induces a biphasic modulation of hypothalamic ANF neurons: a ligand concentration-dependent effect involving D5 and D2 receptor interaction. Molecular psychiatry 33 10673767
1994 Losartan improves the natriuretic response to ANF in rats with high-output heart failure. The Journal of pharmacology and experimental therapeutics 33 8301562
1993 Immunocytochemical localization of atrial natriuretic factor (ANF)-like peptides in the brain and heart of the treefrog Hyla japonica: effect of weightlessness on the distribution of immunoreactive neurons and cardiocytes. The Journal of comparative neurology 33 8468402
2010 PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Hormone research in paediatrics 32 20389107
2007 Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arquivos brasileiros de endocrinologia e metabologia 32 18157385
1992 Role of spleen in ANF-induced reduction in plasma volume. Canadian journal of physiology and pharmacology 32 1473042
1991 Cellular signals regulating the release of ANF. Canadian journal of physiology and pharmacology 32 1838021
1988 Involvement of Ni protein in the functional coupling of the atrial natriuretic factor (ANF) receptor to adenylate cyclase in rat lung plasma membranes. European journal of biochemistry 31 2839333
2009 beta-Catenin/TCF/LEF1 can directly regulate phenylephrine-induced cell hypertrophy and Anf transcription in cardiomyocytes. Biochemical and biophysical research communications 30 19799869
1995 Blood pressure and fluid-electrolyte balance in ANF-transgenic mice on high- and low-salt diets. The American journal of physiology 30 7631892
2011 GATA4 regulates ANF expression synergistically with Sp1 in a cardiac hypertrophy model. Journal of cellular and molecular medicine 29 20874724
1992 Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition. The American journal of physiology 27 1443119
2008 The LIM-domain protein Zyxin binds the homeodomain factor Xanf1/Hesx1 and modulates its activity in the anterior neural plate of Xenopus laevis embryo. Developmental dynamics : an official publication of the American Association of Anatomists 26 18297730
2004 Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK. Biochemical and biophysical research communications 26 15465036
1995 C-type natriuretic peptide and brain natriuretic peptide inhibit adenylyl cyclase activity: interaction with ANF-R2/ANP-C receptors. FEBS letters 26 7649305
2010 Corepressors TLE1 and TLE3 interact with HESX1 and PROP1. Molecular endocrinology (Baltimore, Md.) 25 20181723
2000 Expression of atrial natriuretic factor (ANF) during Xenopus cardiac development. Development genes and evolution 25 11151301
1989 Localization of atrial natriuretic factor (ANF) binding sites in the central nervous system of the frog. The Journal of comparative neurology 25 2522951
2005 Comparative analysis of the natriuretic peptide precursor gene cluster in vertebrates reveals loss of ANF and retention of CNP-3 in chicken. Developmental dynamics : an official publication of the American Association of Anatomists 24 15895405
1995 Effects of urodilatin in the rat kidney: comparison with ANF and interaction with vasoactive substances. Kidney international 24 7643524
1988 ANF inhibits vasopressin-induced Ca2+ mobilization and contraction in glomerular mesangial cells. The American journal of physiology 24 2972215
2012 Characterization of a long-acting recombinant human serum albumin-atrial natriuretic factor (ANF) expressed in Pichia pastoris. Regulatory peptides 23 22296859
2014 Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study. Endocrine 22 25500790
2008 A novel SNP of the Hesx1 gene in bovine and its associations with average daily gain. Molecular biology reports 22 18853282
2005 Osteoblast calcium-sensing receptor has characteristics of ANF/7TM receptors. Journal of cellular biochemistry 22 15962313
1995 Catalytic activation of guanylate cyclase/atrial natriuretic factor receptor by combined effects of ANF and GTP gamma S in plasma membranes of Leydig tumor cells: involvement of G-proteins. Archives of biochemistry and biophysics 22 7840642
1990 Dehydration increases the density of C receptors for ANF on rat glomerular membranes. The American journal of physiology 22 2158751
1988 Blunted cGMP response to ANF in vascular smooth muscle cells of SHR. The American journal of physiology 22 2847533
2013 Identification of HESX1 mutations in Kallmann syndrome. Fertility and sterility 21 23465708
2011 Ca2+-induced PARP-1 activation and ANF expression are coupled events in cardiomyocytes. The Biochemical journal 21 21635224
2006 Conserved regulatory elements establish the dynamic expression of Rpx/HesxI in early vertebrate development. Developmental biology 21 16527264
1999 HESX1: a novel gene implicated in a familial form of septo-optic dysplasia. Acta paediatrica (Oslo, Norway : 1992). Supplement 21 10626545
1991 Studies of ANF processing and secretion using a primary cardiocyte culture model. Canadian journal of physiology and pharmacology 21 1838022
1987 A serum protease cleaves proANF into a 14-kilodalton peptide and ANF. The American journal of physiology 21 2949627
2007 DNMT1 interacts with the developmental transcriptional repressor HESX1. Biochimica et biophysica acta 20 17931718
2000 Sulfonylurea receptor ligands modulate stretch-induced ANF secretion in rat atrial myocyte culture. American journal of physiology. Heart and circulatory physiology 20 10843902
1993 Ascorbic acid enhances forskolin-induced cyclic AMP production and pro-ANF mRNA expression of hypothalamic neurons in culture. Endocrinology 20 8386616
1992 ANF and bradykinin synergistically inhibit transport in M-1 cortical collecting duct cell line. The American journal of physiology 20 1322053
1987 Comparative effect of ANF and various diuretics on isolated nephron segments. Kidney international 20 2953924
1991 Experimental glaucoma significantly decreases atrial natriuretic factor (ANF) receptors in the ciliary processes of the rabbit eye. Experimental eye research 19 1660404
1991 CGRP and ANF cause relaxation of opossum internal anal sphincter via different mechanisms. The American journal of physiology 19 1852117
1990 Photoaffinity labelling of atrial natriuretic factor (ANF)-R1 receptor by underivatized 125I-ANF. Involvement of lipid peroxidation. The Biochemical journal 18 2159278
2010 Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort. American journal of medical genetics. Part A 17 20949537
1995 Localization of mRNA coding for the three subtypes of atrial natriuretic factor (ANF) receptors in rat anterior pituitary gland cells. Journal of neuroendocrinology 16 8745272
1994 Functional characterization of ribozymes expressed using U1 and T7 vectors for the intracellular cleavage of ANF mRNA. Biochemistry 16 7918434
1992 The pharmacokinetics of 125I-atrial natriuretic factor in anaesthetized rats. Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF-C receptor blockade. Biochemical pharmacology 16 1417928
1991 Developing essential hypertension: a syndrome involving ANF deficiency? Canadian journal of physiology and pharmacology 16 1838026
1991 Neutral metalloendopeptidase inhibitors as ANF potentiators: sites and mechanisms of action. Canadian journal of physiology and pharmacology 16 1838029
1991 Proteinase activities in bovine atrium and the possible role of mast cell tryptase in the processing of atrial natriuretic factor (ANF). Comparative biochemistry and physiology. B, Comparative biochemistry 16 1838723
2003 A novel inducible element, activated by contact with Rathke's pouch, is present in the regulatory region of the Rpx/Hesx1 homeobox gene. Developmental biology 15 12885556
1987 Chemical synthesis and structure-activity relations for ANF analogues. Endocrinology and metabolism clinics of North America 15 2962866