Affinage

HOXA3

Homeobox protein Hox-A3 · UniProt O43365

Length
443 aa
Mass
46.4 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXA3 is a homeodomain transcription factor that serves as a master regulator of pharyngeal organ development and participates in diverse post-developmental processes including angiogenesis, haematopoietic specification, and immune cell polarization. Targeted disruption in mice causes athymia, aparathyroidism, thyroid hypoplasia, carotid body agenesis, and cardiovascular defects resembling DiGeorge syndrome, with the primary defect residing in impaired neural crest cell differentiation and third pharyngeal pouch endoderm patterning through a Hoxa3–Pax1–Gcm2 genetic pathway; tissue-specific conditional knockouts demonstrate distinct cell-autonomous roles in neural crest cells (morphogenesis) and endoderm (thymus/parathyroid differentiation) (PMID:1673020, PMID:7635047, PMID:11476574, PMID:25249461). HOXA3 expression in the hindbrain is initiated by kreisler/MafB binding to a dedicated enhancer and subsequently maintained by a Hox/Pbx auto-regulatory loop, while its translation is regulated by a 5′UTR uORF/IRES system requiring eIF2D (PMID:9895323, PMID:11566863, PMID:34076576). In adult contexts, HOXA3 promotes endothelial migration and angiogenesis via transcriptional upregulation of MMP-14 and uPAR, restrains hemogenic endothelium from haematopoietic transition by suppressing Runx1 and activating Jag1-mediated Notch cis-inhibition, and shifts macrophage polarization toward an M2 phenotype through PU.1/Stat6 modulation (PMID:15914537, PMID:21170035, PMID:29073173, PMID:27342843).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    The foundational question—what tissues require Hoxa3—was answered when targeted disruption revealed that Hoxa3 is essential for development of thymus, parathyroid, thyroid, and cardiovascular structures derived from pharyngeal arches/pouches, establishing it as a key regulator of pharyngeal organogenesis.

    Evidence Gene targeting in mouse ES cells with full phenotypic characterization of null embryos

    PMID:1673020

    Open questions at the time
    • Downstream transcriptional targets not identified
    • Cell-autonomous versus non-cell-autonomous roles not distinguished
    • Whether defect is in migration or differentiation of precursor cells unknown
  2. 1995 High

    The cellular mechanism was clarified: Hoxa3 does not affect neural crest cell migration but is required for their subsequent differentiation and for maintaining Pax1 expression in third pharyngeal pouch mesenchyme, placing Pax1 downstream of Hoxa3.

    Evidence DiI neural crest tracing combined with in situ hybridization for Pax1 and genetic epistasis with Pax1 mutants

    PMID:7635047

    Open questions at the time
    • Whether Pax1 is a direct transcriptional target of Hoxa3 not tested
    • Endodermal versus mesenchymal Hoxa3 requirements not separated
  3. 1994 High

    Paralog cooperation was demonstrated: Hoxa3 and Hoxd3 synergistically control atlas vertebra development in a dosage-dependent manner, revealing functional redundancy among group 3 Hox paralogs.

    Evidence Double mutant analysis of independently targeted Hoxa3 and Hoxd3 alleles

    PMID:7913519

    Open questions at the time
    • Molecular basis of paralog synergy (shared versus distinct targets) unknown
    • Whether other paralogs (Hoxb3, Hoxc3) contribute not tested
  4. 1999 High

    Transcriptional regulation of Hoxa3 itself was resolved in two phases: kreisler/MafB directly binds an enhancer to initiate Hoxa3 expression in rhombomeres 5/6, while a separate Hox/Pbx auto-regulatory element maintains expression independently of kreisler.

    Evidence Transgenic enhancer dissection with binding-site mutagenesis in mouse and chick embryos

    PMID:11566863 PMID:9895323

    Open questions at the time
    • Whether other upstream regulators (e.g., retinoic acid) act through these or additional enhancers not fully resolved
    • Chromatin-level regulation not examined
  5. 2001 High

    The Hoxa3–Pax1 genetic pathway was extended to organ-level differentiation: compound Hoxa3+/−;Pax1−/− mutants revealed that this pathway controls apoptosis, proliferation, and Gcm2 expression in pharyngeal pouch endoderm, defining a Hoxa3→Pax1→Gcm2 hierarchy for parathyroid/thymus specification.

    Evidence Compound mutant analysis with fetal liver adoptive transfer, flow cytometry, and in situ hybridization for organ-specific markers

    PMID:10820253 PMID:11476574

    Open questions at the time
    • Direct Hoxa3 binding to Pax1 or Gcm2 regulatory regions not demonstrated
    • Whether additional parallel pathways exist alongside Pax1 not excluded
  6. 2002 High

    Hoxa3's vascular role was established: null mutants show bilateral degeneration of the third arch artery and absence of the carotid body, extending the phenotype beyond endoderm-derived organs to vascular morphogenesis.

    Evidence Null mutant analysis with vascular casting and scanning electron microscopy

    PMID:12074562 PMID:15714286

    Open questions at the time
    • Whether the vascular defect is cell-autonomous in endothelium or secondary to mesenchymal failure not resolved at this stage
  7. 2005 High

    An adult function for HOXA3 was discovered: HOXA3 promotes endothelial cell migration and angiogenesis by transcriptionally upregulating MMP-14 and uPAR, with uPAR required for the migratory response, and HOXA3 gene transfer rescues wound healing in diabetic mice.

    Evidence Endothelial migration assays with uPAR blocking; in vivo angiogenesis and wound healing in diabetic mice

    PMID:15914537

    Open questions at the time
    • Whether MMP-14 and uPAR are direct transcriptional targets not confirmed by promoter binding assays
    • Mechanism in keratinocytes not fully characterized
  8. 2010 High

    HOXA3 was shown to restrain the endothelial-to-haematopoietic transition by suppressing Runx1 and other haematopoietic transcription factors; epistasis established that Runx1 uniquely erases the endothelial identity maintained by HoxA3.

    Evidence Reciprocal gain/loss-of-function in mouse ES cell hemogenic endothelium differentiation with gene expression profiling and epistasis

    PMID:21170035

    Open questions at the time
    • Whether Hoxa3 directly represses Runx1 transcription or acts indirectly not determined
    • In vivo validation in definitive haematopoiesis not provided
  9. 2010 High

    Evolutionary divergence of Hoxa3 function was mapped to the C-terminal domain: zebrafish hoxa3a cannot fully substitute for mouse Hoxa3, and chimeric protein knock-in showed that tissue-specific functions diverged through C-terminal sequence evolution.

    Evidence Knock-in of zebrafish coding sequence into mouse Hoxa3 locus; chimeric protein phenotypic rescue

    PMID:20498049

    Open questions at the time
    • Specific C-terminal residues or interaction surfaces responsible not identified
    • Whether cofactor binding specificity differs not tested
  10. 2014 High

    Cell-type-specific conditional knockouts resolved that HOXA3 is required in neural crest cells for pharyngeal arch morphogenesis and in endoderm for temporal regulation of thymus/parathyroid differentiation, demonstrating distinct cell-autonomous roles in each tissue.

    Evidence Endoderm-Cre and NCC-Cre conditional knockouts with lineage tracing and multi-timepoint phenotyping

    PMID:25249461

    Open questions at the time
    • Direct transcriptional targets in each cell type remain uncharacterized on a genome-wide level
    • Whether mesoderm-intrinsic roles exist not addressed
  11. 2016 Medium

    HOXA3's immunomodulatory role was defined: enforced expression in macrophages promotes M2 polarization through PU.1 and Stat6, accelerating diabetic wound healing, and this function is DNA-binding independent, suggesting a non-canonical (protein–protein interaction) mechanism.

    Evidence Protein transduction of Hoxa3 into macrophages; in vivo diabetic wound assay; western blot for PU.1 and Stat6

    PMID:27342843

    Open questions at the time
    • DNA-binding-independent mechanism not molecularly resolved—protein interaction partners not identified
    • Single laboratory; awaits independent replication
  12. 2017 Medium

    The mechanism by which HOXA3 blocks endothelial-to-haematopoietic transition was extended: HOXA3 upregulates Jag1, causing Notch cis-inhibition in endothelial cells, and Notch activation can override HoxA3 to permit haematopoietic specification.

    Evidence Jag1 knockdown and Notch activation in ES cell-derived hemogenic endothelium with flow cytometry

    PMID:29073173

    Open questions at the time
    • Whether Jag1 is a direct transcriptional target of HOXA3 not demonstrated
    • In vivo relevance in embryonic haematopoiesis not tested
  13. 2021 High

    Translational control of Hoxa3 was elucidated: a 5′UTR uORF acts as a translation inhibitory element requiring the non-canonical initiation factor eIF2D for cap-dependent repression, while an IRES permits cap-independent translation, providing a dual regulatory switch.

    Evidence In vitro translation with uORF mutagenesis and eIF2D depletion; IRES activity assay

    PMID:34076576

    Open questions at the time
    • Physiological conditions under which IRES-dependent translation predominates not defined
    • In vivo relevance of eIF2D-dependent regulation not tested
  14. 2024 Medium

    A human stem cell model confirmed that HOXA3 regulates third pharyngeal pouch endoderm differentiation, proliferation, and migration through transcriptional activation of EPHB2 and downstream Wnt signaling, extending the developmental pathway to human biology.

    Evidence HOXA3 knockdown in hESC-derived 3PPE; EPHB2 expression and Wnt reporter analysis

    PMID:38259452

    Open questions at the time
    • Direct HOXA3 binding to EPHB2 regulatory regions not confirmed
    • Whether Wnt activation is EPHB2-dependent or parallel not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Genome-wide identification of direct HOXA3 transcriptional targets in each relevant cell type (neural crest, pharyngeal endoderm, endothelium, macrophages) by ChIP-seq, and structural resolution of how the C-terminal domain specifies cofactor interactions, remain major open questions.
  • No genome-wide HOXA3 ChIP-seq in pharyngeal tissues published
  • Structural basis for cofactor selectivity and DNA-binding-independent functions unknown
  • In vivo validation of the HOXA3→Runx1 and HOXA3→Jag1 axes in definitive haematopoiesis not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
HOXA2JAG1PAX1PBX1PU.1RUNX1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Targeted disruption of mouse Hoxa3 (hox-1.5) results in athymia, aparathyroidism, thyroid hypoplasia, and craniofacial/cardiovascular defects resembling DiGeorge syndrome, demonstrating Hoxa3 is required for development of pharyngeal arch/pouch-derived structures. Gene targeting (homologous recombination) in mouse ES cells; loss-of-function phenotypic analysis Nature High 1673020
1995 Hoxa3 loss-of-function affects the intrinsic capacity of mesenchymal neural crest cells to differentiate in the pharyngeal region (without altering their migration), and Hoxa3 is required to maintain Pax1 expression in neural crest cells of the third pharyngeal pouch; reduced Pax1 is implicated in the athymic phenotype. Carbocyanine dye (DiI) injection for neural crest cell tracing; in situ hybridization for Pax1; genetic epistasis with Pax1 mutants Development High 7635047
1994 Hoxa3 and Hoxd3 (paralogous Hox genes) interact synergistically in a dosage-dependent manner to control atlas vertebra development; in double mutants the atlas is deleted rather than homeotically transformed, suggesting these paralogs differentially regulate proliferation rates of precursor cells. Genetic epistasis: double mutant analysis of independently targeted Hoxa3 and Hoxd3 alleles Nature High 7913519
1999 The kreisler (Krml1) Maf bZIP transcription factor directly binds a single high-affinity site in a 600 bp enhancer in the Hoxa3 intergenic region, activating Hoxa3 expression specifically in rhombomeres 5 and 6 of the developing hindbrain. Transgenic enhancer analysis; deletion mapping; binding site mutagenesis; ectopic kreisler expression; kreisler loss-of-function Development High 9895323
2001 Hoxa3 expression in rhombomeres 5/6 is maintained in later hindbrain stages via a conserved auto/cross-regulatory enhancer containing two bipartite Hox/Pbx-binding sites, independent of kreisler; this separates initiation (kreisler-dependent) from maintenance (Hox/Pbx auto-regulatory loop) phases of Hoxa3 expression. Transgenic analysis in mouse and chick; cis-element deletion and mutagenesis of Hox/Pbx-binding sites; cross-species conservation analysis Development High 11566863
2001 Hoxa3 and Pax1 act in a genetic pathway to regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis; Hoxa3+/-Pax1-/- compound mutants show increased apoptosis, reduced Gcm2 (parathyroid marker) and delayed/absent organ differentiation, with the defect residing in radio-resistant stromal cells. Compound mutant analysis; fetal liver adoptive transfer; flow cytometry; immunohistochemistry; in situ hybridization for organ-specific markers Developmental Biology High 10820253 11476574
2002 Hoxa3 is essential for development of the carotid body and proper third arch artery morphogenesis; in Hoxa3 null mutants the third arch artery degenerates bilaterally at E10.5–11.5, resulting in absence of the carotid body and malformation of the carotid artery system. Gene-targeted null mutant analysis; immunohistochemistry; vascular casting/scanning electron microscopy Developmental Biology High 12074562
2005 Hoxa3 is required for proliferation and differentiation of third pharyngeal arch mesenchyme; in null mutants, neural crest cell migration is normal but cell proliferation in the third arch is reduced, and arch fusion is delayed, leading to third arch artery regression. Connexin43-lacZ transgene for neural crest cell lineage tracing; BrdU proliferation assay; immunohistochemistry on null mutant embryos Cell and Tissue Research High 15714286
2005 HOXA3 promotes endothelial and keratinocyte cell migration, induces angiogenesis in vivo, and transcriptionally upregulates MMP-14 and uPAR in endothelial cells; migration is uPAR-dependent. HOXA3 gene transfer rescues angiogenesis and wound closure defects in diabetic mice. Gene transfer (plasmid) in vivo; endothelial cell migration assay in vitro; in vivo angiogenesis assay; qPCR/western blot for MMP-14 and uPAR; uPAR blocking experiments Journal of Cell Science High 15914537
2010 HoxA3 restrains haematopoietic differentiation of haemogenic endothelium by downregulating key haematopoietic transcription factors including Runx1, Gata1, Gfi1B, Ikaros, and PU.1; Runx1 is uniquely able to erase the endothelial program maintained by HoxA3. Loss- and gain-of-function epistasis demonstrates HoxA3 acts upstream of Runx1 in the endothelial-to-haematopoietic transition. Loss-of-function and gain-of-function in mouse ES cell differentiation system; gene expression profiling; epistasis experiments; flow cytometry for endothelial/haematopoietic markers Nature Cell Biology High 21170035
2010 Mouse and zebrafish Hoxa3 orthologs are not functionally interchangeable; using a chimeric allele knock-in, the difference maps primarily to the C-terminal domain of the protein, demonstrating that Hox protein function can evolve independently in different cell types. Knock-in of zebrafish hoxa3a coding sequence into the mouse Hoxa3 locus; chimeric protein allele analysis; phenotypic rescue assays in multiple tissues PNAS High 20498049
2014 HOXA3 has distinct, tissue-specific cell-autonomous and non-cell-autonomous roles in pharyngeal organ development: primarily required in neural crest cells (NCCs) for morphogenesis/migration, and in endoderm for temporal regulation of the thymus program and cell-autonomous parathyroid differentiation. Tissue-specific conditional knockout using endoderm-Cre and NCC-Cre drivers; Hoxa3-Cre lineage analysis; phenotypic analysis at multiple timepoints Development High 25249461
2009 HOXA3 gene transfer to diabetic wounds increases mobilization and recruitment of endothelial progenitor cells (EPCs) from bone marrow, suppresses NF-κB pathway gene expression (including MyD88 and TOLLIP), and reduces inflammatory cell recruitment, thereby accelerating wound repair. GFP bone marrow chimeras; microarray analysis of HOXA3-treated wounds; flow cytometry for EPC and inflammatory cell populations Stem Cells High 19544454
2010 Hoxa3 overexpression in diabetic-derived Gr-1+CD11b+ myeloid cells reverses their diabetic phenotype, restoring their ability to stimulate neovascularization and correcting defects in proliferation, chemotaxis, adhesion, and differentiation. Ex vivo retroviral transduction of bone marrow-derived Gr-1+CD11b+ cells; in vivo neovascularization assay; functional assays for chemotaxis, adhesion, differentiation Blood Medium 20974673
2016 Hoxa3 enforced expression in macrophages inhibits M1 (classical) polarization and promotes M2 (alternative) polarization, in part through regulation of PU.1/Spi1 and Stat6, and accelerates healing in diabetic wounds in a DNA-binding independent manner. Protein transduction of Hoxa3 into macrophages in vitro; in vivo wound healing in diabetic mice; immunohistochemistry for M1/M2 markers (Nos2, Arg1, VEGF); western blot for PU.1 and Stat6 Journal of Immunology Medium 27342843
2003 Targeted overexpression of Hoxa3 in the rostral hindbrain (rhombomeres 1–4) leads to ectopic generation of somatic motoneurones and repression of the dorsoventral patterning gene Irx3, demonstrating Hoxa3 can specify motoneurone identity and acts upstream of Irx3. In ovo electroporation for targeted Hoxa3 overexpression; heterotopic rhombomere transplantation; retinoic acid bead implantation; ISH for Hoxa3, Hoxd4, Irx3 Development Medium 12756180
2001 Hoxa3 is required for correct axon projection patterns of all three components of the IXth (glossopharyngeal) nerve, including motor neurons, proximal ganglion sensory neurons, and distal ganglion placode-derived neurons; loss of Hoxa3 causes abnormal caudal migration of neural crest cells and defective placode cell migration. Analysis of Hoxa3 null mutant embryos; neural crest and placode cell fate mapping by ISH and immunohistochemistry Developmental Biology Medium 11784044
2017 HoxA3 prevents endothelial-to-haematopoietic transition (EHT) also by inducing Jag1 ligand upregulation in endothelial cells, causing cis-inhibition of the Notch pathway; Notch activation or Jag1 knockdown can downregulate the endothelial phenotype as a prerequisite for EHT, even in the presence of HoxA3. Gain- and loss-of-function in hemogenic endothelium ES cell system; Jag1 knockdown; Notch pathway activation; flow cytometry PLoS One Medium 29073173
2020 GDF11 promotes HOXA3 overexpression through the Smad2/3 signaling pathway; HOXA3 then binds the NLRP3 promoter (confirmed by ChIP assay) to suppress NLRP3-mediated cardiomyocyte pyroptosis in myocardial infarction. AAV9-mediated GDF11 overexpression in mice; ChIP assay for HOXA3 binding to NLRP3 promoter; western blot for Smad2/3 pathway; PROMO/JASPAR prediction Cell Death & Disease Medium 33100331
2021 The Hoxa3 5'UTR contains a translation inhibitory element (TIE) with an upstream ORF (uORF) that inhibits cap-dependent translation; the non-canonical initiation factor eIF2D is required for this uORF-mediated cap-dependent translation inhibition, while an IRES enables cap-independent translation. In vitro translation assay; mutagenesis of uORF; eIF2D knockdown/depletion experiments; IRES activity assay eLife High 34076576
2021 In the context of PRRSV infection, HOXA3 negatively regulates HO-1 gene transcription; reduced HO-1 weakens the HO-1–IRF3 interaction, inhibiting IRF3 phosphorylation and nuclear translocation, thereby suppressing type I IFN production and promoting viral immune evasion. Co-immunoprecipitation (HO-1/IRF3 interaction); HOXA3 knockdown and overexpression; IRF3 nuclear translocation assay; IFN-β and ISG expression measurement Journal of Virology Medium 34851144
2024 HOXA3 regulates the differentiation, proliferation, and migration of third pharyngeal pouch endoderm (3PPE) derived from human embryonic stem cells, acting through transcriptional activation of EPHB2, which in turn activates the Wnt signaling pathway. hESC differentiation to 3PPE; HOXA3 knockdown; EPHB2 expression analysis; Wnt pathway reporter assays; functional assays for proliferation and migration Frontiers in Immunology Medium 38259452
2021 HOXA2 and HOXA3 can heterodimerise with each other, and the highest enriched motif in HOXA2 ChIP-seq peaks in vivo is not recognized by HOXA2 in vitro, highlighting that HOX binding specificity is context-dependent. In vitro DNA binding assays; ChIP-seq; protein-protein interaction assays for heterodimerization Journal of Developmental Biology Medium 34940502
2019 Hoxa3 protein transduction in human diabetic macrophages rescues maturation and inflammatory defects by upregulating RUNX1, modulating p65/NF-κB levels, and altering histone acetyltransferase/deacetylase activity, as well as inhibiting acetylation of the TNF promoter. Hoxa3 protein transduction into primary human macrophages; western blot for RUNX1 and p65/NF-κB; ChIP for histone acetylation at TNF promoter; flow cytometry PLoS One Medium 31626638

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 755 1673020
1991 Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 637 1680563
1992 Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. Nature 481 1346922
1995 The role of Hoxa-3 in mouse thymus and thyroid development. Development (Cambridge, England) 354 7635047
1990 Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice. Cell 347 1970515
1993 Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development (Cambridge, England) 309 7903632
1992 Identification of a retinoic acid responsive enhancer 3' of the murine homeobox gene Hox-1.6. Mechanisms of development 245 1360810
1989 Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox-1.1 in transgenic mice. Cell 240 2568891
1994 Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions. Nature 226 7913519
1990 The segment-specific gene Krox-20 encodes a transcription factor with binding sites in the promoter region of the Hox-1.4 gene. The EMBO journal 190 1969796
1989 Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature 185 2563568
1989 Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue-dependent differences in their regulation. Development (Cambridge, England) 184 2576400
1993 Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes & development 167 7901120
1988 Mouse homeobox gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of Hox-3.1 and Hox-1.5. Development (Cambridge, England) 134 2904354
1993 The establishment of murine Hox-1 expression domains during patterning of the limb. Developmental biology 131 8099045
1989 The Hox-1.3 homeo box protein is a sequence-specific DNA-binding phosphoprotein. Genes & development 130 2565857
1987 Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex. The EMBO journal 118 2891503
1986 A new homeo-box is present in overlapping cosmid clones which define the mouse Hox-1 locus. The EMBO journal 118 3019676
2001 Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Developmental biology 113 11476574
1993 The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene. Genes & development 110 8095481
2005 HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair. Journal of cell science 106 15914537
1987 Differential expression of the mouse homeobox-containing gene Hox-1.4 during male germ cell differentiation and embryonic development. Proceedings of the National Academy of Sciences of the United States of America 104 2441396
1999 Conserved and distinct roles of kreisler in regulation of the paralogous Hoxa3 and Hoxb3 genes. Development (Cambridge, England) 103 9895323
1991 Separate elements cause lineage restriction and specify boundaries of Hox-1.1 expression. Development (Cambridge, England) 101 1685116
1989 The mouse Hox-1.4 gene: primary structure, evidence for promoter activity and expression during development. Development (Cambridge, England) 101 2576648
1987 Homoeobox gene Hox-1.5 expression in mouse embryos: earliest detection by in situ hybridization is during gastrulation. Development (Cambridge, England) 98 2452725
1993 Sequences 5' of the homeobox of the Hox-1.4 gene direct tissue-specific expression of lacZ during mouse development. Development (Cambridge, England) 91 8100763
2004 Retinoic acid signaling acts via Hox1 to establish the posterior limit of the pharynx in the chordate amphioxus. Development (Cambridge, England) 88 15576409
2001 Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms. Development (Cambridge, England) 85 11566863
1990 Position-specific activity of the Hox1.1 promoter in transgenic mice. Development (Cambridge, England) 75 1971214
2006 Reversal of Hox1 gene subfunctionalization in the mouse. Developmental cell 74 16890163
1987 Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression. Molecular and cellular biology 74 2891029
2010 HoxA3 is an apical regulator of haemogenic endothelium. Nature cell biology 68 21170035
1988 Differential expression of the homeobox gene Hox-1.3 in F9 embryonal carcinoma cells. Proceedings of the National Academy of Sciences of the United States of America 66 2456573
2020 GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3. Cell death & disease 65 33100331
2019 LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells. Oncogenesis 61 31615976
2000 Hoxa3 and pax1 transcription factors regulate the ability of fetal thymic epithelial cells to promote thymocyte development. Journal of immunology (Baltimore, Md. : 1950) 61 10820253
2019 LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis. Human gene therapy 59 30375256
1992 Murine Hox-1.11 homeobox gene structure and expression. Proceedings of the National Academy of Sciences of the United States of America 59 1352886
2003 Expression of Raldh2, Cyp26 and Hox-1 in normal and retinoic acid-treated Ciona intestinalis embryos. Gene expression patterns : GEP 56 12799071
1998 Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1. Teratology 54 9894676
1996 Rhombomere of origin determines autonomous versus environmentally regulated expression of Hoxa-3 in the avian embryo. Development (Cambridge, England) 54 8631267
2002 Conserved regulation of the Caenorhabditis elegans labial/Hox1 gene ceh-13. Developmental biology 53 11820809
2002 Homeobox gene hoxa3 is essential for the formation of the carotid body in the mouse embryos. Developmental biology 53 12074562
1987 A mouse homeo box gene, Hox-1.5, and the morphological locus, Hd, map to within 1 cM on chromosome 6. Genetics 49 2887485
2017 HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway. Journal of cellular biochemistry 47 29073728
2003 Somatic motoneurone specification in the hindbrain: the influence of somite-derived signals, retinoic acid and Hoxa3. Development (Cambridge, England) 45 12756180
1991 Isolation and mapping of EVX1, a human homeobox gene homologous to even-skipped, localized at the 5' end of HOX1 locus on chromosome 7. Nucleic acids research 45 1684419
2012 Retinoic acid-driven Hox1 is required in the epidermis for forming the otic/atrial placodes during ascidian metamorphosis. Development (Cambridge, England) 42 22573621
1988 Genetic analysis and developmental regulation of testis-specific RNA expression of Mos, Abl, actin and Hox-1.4. Oncogene 42 2895445
2005 Hoxa3 regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice. Cell and tissue research 38 15714286
2014 Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development (Cambridge, England) 37 25249461
2009 Hoxa3 and signaling molecules involved in aortic arch patterning and remodeling. Cell and tissue research 35 19290546
2009 HOXA3 modulates injury-induced mobilization and recruitment of bone marrow-derived cells. Stem cells (Dayton, Ohio) 35 19544454
2010 Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells. Blood 34 20974673
2003 Disruption of the Hoxa3 homeobox gene results in anomalies of the carotid artery system and the arterial baroreceptors. Cell and tissue research 33 12658442
2005 Identification and linkage mapping of the genes for the putative homeodomain protein (hox1) and the putative pheromone receptor protein homologue (rcb1) in a bipolar basidiomycete, Pholiota nameko. Current genetics 32 16096791
2018 TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEK/ERK pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 30551418
2004 The role of Hoxa3 gene in parathyroid gland organogenesis of the mouse. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 29 15100241
2018 Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis. International journal of oncology 28 30066858
2010 Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function. Proceedings of the National Academy of Sciences of the United States of America 28 20498049
2007 Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese population. Oncology reports 28 17203192
2011 A retinoic acid responsive Hoxa3 transgene expressed in embryonic pharyngeal endoderm, cardiac neural crest and a subdomain of the second heart field. PloS one 27 22110697
1993 Conservation and divergence of patterns of expression and lineage-specific transcripts in orthologues and paralogues of the mouse Hox-1.4 gene. Developmental biology 27 7680626
2021 Induction of HOXA3 by Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Response through Negative Regulation of HO-1 Transcription. Journal of virology 26 34851144
2016 Enforced Expression of Hoxa3 Inhibits Classical and Promotes Alternative Activation of Macrophages In Vitro and In Vivo. Journal of immunology (Baltimore, Md. : 1950) 26 27342843
2001 Hoxa3 regulates integration of glossopharyngeal nerve precursor cells. Developmental biology 26 11784044
2008 Evolution of the thyroid: anterior-posterior regionalization of the Oikopleura endostyle revealed by Otx, Pax2/5/8, and Hox1 expression. Developmental dynamics : an official publication of the American Association of Anatomists 25 18386819
2009 Epidermal expression of Hox1 is directly activated by retinoic acid in the Ciona intestinalis embryo. Developmental biology 24 19782671
2019 miR-10b suppresses cell invasion and metastasis through targeting HOXA3 regulated by FAK/YAP signaling pathway in clear-cell renal cell carcinoma. BMC nephrology 23 30975094
2016 Temporal and spatial requirements for Hoxa3 in mouse embryonic development. Developmental biology 20 27178667
1992 Hox-1.11 and Hox-4.9 homeobox genes. Proceedings of the National Academy of Sciences of the United States of America 19 1348361
2021 ARID1B/SUB1-activated lncRNA HOXA-AS2 drives the malignant behaviour of hepatoblastoma through regulation of HOXA3. Journal of cellular and molecular medicine 18 33683826
2018 Hox genes in the pharyngeal region: how Hoxa3 controls early embryonic development of the pharyngeal organs. The International journal of developmental biology 18 30604847
2019 Dysregulation of macrophage development and phenotype in diabetic human macrophages can be rescued by Hoxa3 protein transduction. PloS one 17 31626638
2020 LINC00689 induces gastric cancer progression via modulating the miR-338-3p/HOXA3 axis. The journal of gene medicine 16 32926751
2020 A six-amino-acid motif is a major determinant in functional evolution of HOX1 proteins. Genes & development 16 33184220
2016 Chicken gga-miR-130a targets HOXA3 and MDFIC and inhibits Marek's disease lymphoma cell proliferation and migration. Molecular biology reports 16 27178573
1990 Alternatively spliced Hox-1.7 transcripts encode different protein products. DNA sequence : the journal of DNA sequencing and mapping 15 1983703
1989 Progressive restriction in the distribution of the Hox-1.3 homeodomain protein during embryogenesis. Journal of neuroscience research 13 2689656
2002 Stage-specific changes in fetal thymocyte proliferation during the CD4-8- to CD4+8+ transition in wild type, Rag1-/-, and Hoxa3,Pax1 mutant mice. BMC immunology 11 12241558
2007 Expression of homeotic genes Hoxa3, Hoxb3, Hoxd3 and Hoxc4 is decreased in the lungs but not in the hearts of adriamycin-exposed mice. Pediatric surgery international 10 17211587
2021 Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition. eLife 9 34076576
2013 Identification of a retinoic acid-responsive neural enhancer in the Ciona intestinalis Hox1 gene. Development, growth & differentiation 9 23302037
2011 Chicken HOXA3 gene: its expression pattern and role in branchial nerve precursor cell migration. International journal of biological sciences 9 21278919
1993 Protein product of the somatic-type transcript of the Hoxa-4 (Hox-1.4) gene binds to homeobox consensus binding sites in its promoter and intron. Journal of cellular biochemistry 8 7901228
2024 HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway. Frontiers in immunology 7 38259452
2019 miR‑338‑3p suppresses the malignancy of T‑cell lymphoblastic lymphoma by downregulating HOXA3. Molecular medicine reports 7 31322185
2023 ENPP4 and HOXA3 as potential leukaemia stem cell markers in acute myeloid leukaemia. The Malaysian journal of pathology 5 37119247
2023 HOXA3 accelerates wound healing in diabetic and aged non-diabetic mammals. Scientific reports 5 37337031
2014 Secreted HoxA3 Promotes Epidermal Proliferation and Angiogenesis in Genetically Modified Three-Dimensional Composite Skin Constructs. Advances in wound care 5 25302136
2010 HOX-1 and COX-2: Two differentially regulated key mediators of skeletal myoblast tolerance under oxidative stress. Free radical research 5 20370564
1991 Murine embryonic spinal cord and adult testis Hox-1.4 cDNAs are identical 3' to the homeo box. DNA sequence : the journal of DNA sequencing and mapping 5 1686835
2017 Notch activation is required for downregulation of HoxA3-dependent endothelial cell phenotype during blood formation. PloS one 4 29073173
1993 Multiple levels of regulation exist for expression of the Hoxa-4 (Hox-1.4) gene in the mouse testis. Cellular & molecular biology research 4 7909702
2025 High expression and regulatory mechanisms of ANGPT1 and HOXA3 in acute myeloid leukemia. Bulletin du cancer 3 40107921
2024 Epigenetic regulation of HOXA3 and its impact on oral squamous cell carcinoma progression. Oral surgery, oral medicine, oral pathology and oral radiology 3 39658479
2021 Molecular Characterization of HOXA2 and HOXA3 Binding Properties. Journal of developmental biology 3 34940502
2017 Escapees from Rhombomeric Lineage Restriction: Extensive Migration Rostral to the r4/r5 Border of Hox-a3 Expression. Anatomical record (Hoboken, N.J. : 2007) 3 28667681
2014 The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis. Journal of pediatric endocrinology & metabolism : JPEM 3 24127533