Affinage

HOXB1

Homeobox protein Hox-B1 · UniProt P14653

Length
301 aa
Mass
32.2 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXB1 is a homeodomain transcription factor that specifies and maintains rhombomere 4 (r4) identity in the developing hindbrain, controlling the specification, migration, and survival of facial branchiomotor and vestibuloacoustic efferent neurons. It binds DNA cooperatively with Pbx1 cofactors via a hexapeptide motif that inserts into a hydrophobic pocket on Pbx1, and assembles higher-order complexes with Prep1-Pbx heterodimers on its own autoregulatory enhancer and on downstream target genes including Hoxb2, Hoxa2, EphA2, and GATA2/GATA3 (PMID:7600572, PMID:10052460, PMID:9242495, PMID:17113575, PMID:10556076). Its expression is established through retinoic acid-responsive elements (3' DR5 and 5' DR2 RAREs) and a SOX/OCT-dependent mechanism on its autoregulatory enhancer, and is negatively regulated by Hoxb3 binding to the Hoxb1 locus (PMID:7914354, PMID:7916164, PMID:11278854, PMID:21320481). A homozygous HOXB1 missense mutation (Arg207Cys) that disrupts homeodomain-DNA minor-groove contacts causes hereditary congenital bilateral facial palsy with hearing loss in humans, recapitulating the mouse knockout phenotype (PMID:22770981).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 High

    The mechanism by which retinoic acid controls initial HOXB1 neuroectodermal expression was established: a 3' RARE is required for early expression and a separate repressor RARE restricts expression to r4, showing that retinoid signaling both activates and spatially sharpens HOXB1 transcription.

    Evidence Transgenic mouse analysis with RARE point mutations across mouse, chicken, and pufferfish regulatory regions

    PMID:7914354 PMID:7916164

    Open questions at the time
    • Identity of the trans-acting factors conferring repressor vs. activator RARE function was not determined
    • Whether these RAREs function cell-autonomously in neuroectoderm was not tested
  2. 1995 High

    The positive autoregulatory loop maintaining HOXB1 expression in r4 was discovered, revealing that Hoxb1 requires Pbx/Exd cofactors for cooperative DNA binding to its own regulatory region — the first demonstration that Hox autoregulation is cofactor-dependent.

    Evidence In vitro DNA binding assays plus transgenic mouse and Drosophila embryo functional analysis with mutational dissection

    PMID:7600572

    Open questions at the time
    • The structural basis of the Hoxb1-Pbx interaction was not yet resolved
    • Whether additional cofactors (e.g., Prep/Meis) participate in the autoregulatory complex was unknown
  3. 1995 Medium

    Two distinct retinoic acid response pathways controlling HOXB1 (a 5' DR2 and a 3' DR2/DR5) were functionally dissected, each utilizing different tissue-specific RA-dependent coactivators, establishing that HOXB1 integrates multiple RA-sensing mechanisms.

    Evidence Promoter element dissection by transfection and reporter assays in cell lines

    PMID:7831296 PMID:7831297

    Open questions at the time
    • The identities of the tissue-specific RA-inducible coactivators were not determined
    • In vivo validation in transgenic embryos was not performed in these studies
  4. 1996 High

    The developmental requirement for Hoxb1 was established by gene knockout: Hoxb1 maintains (but does not initiate) r4 identity and is essential for specification and migration of facial branchiomotor and vestibuloacoustic efferent neurons that form the VIIth nerve.

    Evidence Two independent targeted null alleles in mice with DiI tracing, lineage analysis, and molecular marker analysis

    PMID:8898234 PMID:8967950

    Open questions at the time
    • Whether Hoxb1 acts cell-autonomously in motor neurons versus their environment was unresolved
    • Downstream transcriptional targets mediating migration were unknown
  5. 1997 High

    Hoxb2 was identified as a direct transcriptional target of Hoxb1 in r4, demonstrating that Hoxb1 cross-regulates paralogous Hox genes through bipartite Hox/Pbx binding motifs to build the r4 gene regulatory network.

    Evidence In vitro cooperative DNA binding, transgenic gain-of-function, and Hoxb1 mutant loss-of-function analysis

    PMID:9242495

    Open questions at the time
    • Whether Hoxb2 mediates any specific aspect of the Hoxb1 KO phenotype was not shown
  6. 1998 High

    The regulatory hierarchy upstream of Hoxb1 was refined: the 3' RARE establishes early high-level expression, Hoxa1 pararegulates Hoxb1, and both are required for initial EphA2 activation in r4; EphA2 was confirmed as a direct Hox/Pbx transcriptional target.

    Evidence Double mutant genetic epistasis (Hoxa1/Hoxb1), in vitro EMSA, transactivation assays, and transgenic enhancer analysis

    PMID:9463349 PMID:9671595 PMID:9733765

    Open questions at the time
    • The functional significance of EphA2 activation for r4 identity or neuron migration was not tested
    • Whether the DR5 RARE gut expression has functional consequences was unresolved
  7. 1999 High

    The atomic mechanism of Hoxb1-Pbx1 cooperative DNA binding was resolved: the crystal structure revealed the hexapeptide inserts into a hydrophobic pocket formed partly by a Pbx1-specific three-amino-acid insertion and a fourth alpha-helix that folds upon DNA binding, establishing an ordered assembly mechanism.

    Evidence X-ray crystallography at 2.35 Å and multidimensional NMR of Pbx1 free versus DNA-bound

    PMID:10052460 PMID:10448033

    Open questions at the time
    • Whether hexapeptide-pocket interactions are druggable or regulable was unknown
    • The structural basis for Hox paralog specificity toward Pbx was not addressed
  8. 1999 High

    GATA2 and GATA3 were placed downstream of Hoxb1 in a transcriptional cascade controlling r4 ventral neuron specification, and ectopic Hoxb1 was shown to be sufficient to induce ectopic GATA2/3 in adjacent rhombomeres.

    Evidence Hoxb1 knockout and GATA2 knockout epistasis, ectopic Hoxb1 transgenic expression, in situ hybridization

    PMID:10556076

    Open questions at the time
    • Whether GATA2/3 are direct or indirect targets of Hoxb1 was not determined
    • The identity of GATA2/3-dependent effector genes in r4 was unknown
  9. 2000 High

    Hoxb1 was shown to control the entire dorsoventral axis of r4 progenitor specification, acting upstream of Shh and Mash1 pathways; its absence triggers programmed cell death of multiple neuronal populations, extending its role beyond motor neuron migration.

    Evidence Hoxb1 knockout with DV patterning marker analysis and progenitor population quantification

    PMID:11076756

    Open questions at the time
    • Whether Hoxb1 directly regulates Shh or Mash1 pathway components was not tested
    • The mechanism by which Hoxb1 loss triggers apoptosis was unknown
  10. 2001 High

    The Hoxb1 autoregulatory enhancer was shown to integrate SOX/OCT and HOX/PBX inputs combinatorially, and the HOXB1 N-terminal domain was identified as conferring higher transcriptional activity than HOXA1, explaining paralog-specific function at shared binding sites.

    Evidence Reporter assays with SOX/OCT site mutagenesis, domain mapping, transgenic mouse analysis, Hoxa1 mutant analysis

    PMID:11278854

    Open questions at the time
    • Which SOX and OCT family members operate in vivo at this enhancer in r4 was not determined
  11. 2002 High

    Conservation of Hoxb1 function in controlling VIIth nerve motor neuron migration was confirmed in zebrafish, and RNA rescue experiments demonstrated that paralogs hoxb1a and hoxb1b are biochemically non-interchangeable.

    Evidence Morpholino knockdown with mRNA rescue in zebrafish, neuroanatomical analysis

    PMID:11973267

    Open questions at the time
    • The molecular basis of paralog non-equivalence was not identified
  12. 2003 High

    The structural mechanism for combinatorial control at the Hoxb1 enhancer was resolved at the atomic level: NMR of the Oct1·Sox2·Hoxb1-DNA complex showed Sox2 locks Oct1-POUS orientation on DNA through a hydrophobic interface, increasing binding specificity. Separately, Hoxb1 mutant r4 neurons were shown to undergo homeotic re-specification toward r2-like (trigeminal) identity.

    Evidence Solution NMR with residual dipolar couplings; single and compound Hoxb1/Hoxa1/Hoxb2 mutant mice with migration and marker analysis

    PMID:14522873 PMID:14559893

    Open questions at the time
    • Whether the Oct1-Sox2 interaction is required in vivo for Hoxb1 r4 expression was not tested genetically
    • Whether r2 re-specification is a default state or requires active reprogramming was unknown
  13. 2004 High

    Hoxb1 was shown to function cell-autonomously in both motor neurons and neural crest-derived glia for VIIth nerve circuit formation, using conditional deletion to separate these lineage-specific requirements.

    Evidence Conditional Cre/loxP deletion of Hoxb1 in neural crest with lineage tracing and neural crest cell culture

    PMID:15198977

    Open questions at the time
    • The direct transcriptional targets of Hoxb1 in neural crest-derived glia were not identified
  14. 2005 High

    The autoregulatory enhancer architecture was refined: Prep1-Pbx and Pbx-Hoxb1 binding sites were shown to form ternary complexes, with a high-affinity Prep1-Pbx site (R2/PM3) acting as an inhibitor of ternary complex formation, providing a built-in negative regulatory mechanism.

    Evidence In vitro binding assays with site mutagenesis plus transgenic mouse and chicken embryo validation

    PMID:16166636

    Open questions at the time
    • Whether the inhibitory PM site is regulated dynamically during development was not tested
  15. 2006 High

    Hoxa2 was identified as another direct transcriptional target of Hoxb1 in r4, expanding the network of cross-regulated Hox genes controlled by Hoxb1 through conserved Hox/Pbx binding sites.

    Evidence Comparative genomics across 12 vertebrate species, in vitro binding, mutagenesis, and transgenic analysis with ectopic HOXB1

    PMID:17113575

    Open questions at the time
    • The functional consequence of Hoxa2 loss specifically in r4 downstream of Hoxb1 was not tested
  16. 2011 High

    A negative regulatory loop was identified in which Hoxb3 directly binds and represses the Hoxb1 locus, establishing a mechanism for temporal restriction of Hoxb1 expression after initial r4 specification.

    Evidence EMSA, in vivo ChIP in P19 cells and hindbrain tissue, chick in ovo luciferase reporter, gain-of-function transgenic mice

    PMID:21320481

    Open questions at the time
    • Whether other posterior Hox genes similarly repress Hoxb1 was not tested
    • The developmental timing of Hoxb3-mediated repression relative to autoregulatory maintenance was not precisely defined
  17. 2012 High

    The human disease relevance was established: a homozygous HOXB1 missense mutation (Arg207Cys) causing hereditary congenital facial paresis was shown to disrupt DNA minor-groove contacts and destabilize the HOXB1:PBX1:DNA complex, directly linking the cooperative binding mechanism to human pathology.

    Evidence Human genetic study, molecular modeling, in vitro DNA-protein binding assay

    PMID:22770981

    Open questions at the time
    • Whether residual HOXB1 activity remains in Arg207Cys patients was not quantified
    • No rescue experiment in model organisms with the human mutation was performed
  18. 2015 Medium

    Beyond the hindbrain, Hoxb1 was shown to regulate second heart field development by restraining FGF/ERK and BMP/SMAD signaling and preventing premature myocardial differentiation of cardiac progenitors.

    Evidence Hoxb1 knockout mice with cardiac morphological and signaling pathway analysis

    PMID:26284287

    Open questions at the time
    • Whether Hoxb1 directly regulates FGF or BMP pathway components or acts indirectly was not determined
    • The Hoxb1-expressing cardiac progenitor population was not precisely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the full catalog of direct Hoxb1 transcriptional targets genome-wide (by ChIP-seq in r4), the structural basis for Hox paralog specificity in Pbx complex function, and the mechanism by which Hoxb1 loss triggers apoptosis of r4 progenitors.
  • No genome-wide direct target map in r4 tissue exists
  • Structural basis for paralog-specific Pbx complex activity is unresolved
  • Mechanism linking Hoxb1 loss to progenitor cell death is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-74160 Gene expression (Transcription) 7
Partners
HOXA1HOXB3PBX1POU2F1PREP1SOX2
Complex memberships
HoxB1-Pbx1-DNA ternary complexOct1-Sox2-Hoxb1-DNA complexPrep1-Pbx1-HoxB1 ternary complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Hoxb-1 autoregulates its own expression in rhombomere 4 through a positive autoregulatory loop requiring cooperative binding with Pbx/Exd cofactors to conserved sequence motifs in its regulatory region; in vitro binding of Hoxb-1 to these elements requires Pbx cofactors, and in vivo expression mediated by the r4 enhancer depends on both labial (Hoxb-1 ortholog) and extradenticle (Pbx ortholog) in Drosophila. In vitro DNA binding assays, transgenic mouse and Drosophila embryo functional analysis, deletion and mutational analysis of conserved regulatory elements Cell High 7600572
1994 A retinoic acid response element (RARE) in a 3' enhancer of Hoxb-1 is required for early expression in neuroectoderm and mediates the ectopic response to retinoic acid; point mutations in the RARE abolish neuroectodermal expression in transgenic mice. Transgenic mouse analysis with point mutations in conserved RARE within identified enhancers; comparison across mouse, chicken, and pufferfish Nature High 7914354
1994 A conserved RARE in a repressor element of Hoxb-1 cooperates with a positive enhancer to restrict expression to rhombomere 4; point mutations in this RARE allow expression to spread into adjacent rhombomeres r3 and r5, indicating retinoids sharpen segment-restricted expression during boundary formation. Regulatory analysis in chick and mouse Hoxb-1 genes, transgenic mouse assays with RARE point mutations Science High 7916164
1999 Crystal structure (2.35 Å) of the HoxB1-Pbx1 heterodimer bound to DNA revealed that the HoxB1 hexapeptide inserts into a hydrophobic pocket in Pbx1 formed partly by a three-amino-acid insertion; Pbx1 contains an additional fourth alpha-helix that contributes to hexapeptide binding and stable DNA association. X-ray crystallography of ternary HoxB1-Pbx1-DNA complex at 2.35 Å resolution Cell High 10052460
1996 Loss of Hoxb-1 in mice leads to loss of r4 identity maintenance (not initiation), and r4-derived facial branchiomotor (FBM) and contralateral vestibuloacoustic efferent (CVA) neurons fail to migrate to their proper positions; instead they form an ectopic motor nucleus, demonstrating Hoxb-1 controls migratory properties of hindbrain motor neurons. Targeted gene knockout in mice, DiI tracing of motor neurons, lineage analysis, molecular marker analysis Nature High 8967950
1996 Targeted disruption of Hoxb-1 results in failure to form the somatic motor component of the VIIth (facial) nerve, likely through failure to specify these neurons; the phenotype resembles Bell's Palsy and Moebius Syndrome. Gene targeting in mice (two independent targeted alleles disrupting homeodomain and/or first exon), histological and neuroanatomical analysis Development High 8898234
1997 Hoxb1 directly cross-regulates Hoxb2 expression in rhombomere 4 through a bipartite Hox/Pbx binding motif in the Hoxb2 r4 enhancer; Hoxb1 cooperatively binds this site in a Pbx/Exd-dependent manner in vitro, and the endogenous Hoxb2 gene is no longer upregulated in r4 in Hoxb1 homozygous mutant embryos. Deletion analysis in transgenic mice, in vitro DNA binding assays (cooperative binding), ectopic expression in transgenic mice, Hoxb1 mutant analysis Genes & Development High 9242495
1998 HOXA1 and HOXB1 proteins, in combination with Pbx1, bind to multiple Hox-Pbx consensus sites in the EphA2 (Eck) r4 enhancer in vitro and transactivate EphA2 enhancer-dependent reporter expression; EphA2 expression is reduced in hoxa1/hoxb1 double mutant mice, establishing EphA2 as a direct transcriptional target of these Hox proteins in r4. In vitro DNA binding (EMSA), co-transfection transactivation assays, transgenic enhancer analysis, double mutant mouse analysis Journal of Biological Chemistry High 9733765
1999 GATA2 and GATA3 lie downstream of Hoxb1 in a transcriptional cascade in r4: absence of Hoxb1 causes loss of GATA2 expression in r4, which in turn causes loss of GATA3 expression; ectopic Hoxb1 in the hindbrain induces ectopic GATA2 and GATA3 in ventral r2 and r3. Hoxb1 knockout analysis, GATA2 knockout analysis, ectopic Hoxb1 expression in transgenic mice, in situ hybridization Development High 10556076
1995 HOXB1 gene activation is controlled by a tripartite retinoic acid-triggered cascade: a DR-2 sequence targeted by the RAR-RXR heterodimer, a motif for a RA-inducible tissue-specific coactivator (retinoid-inducible protein), and a proximal autoregulatory site for HOXB1 itself; neither enhancer alone is functional but combined they strongly activate HOXB1 in a cell-specific and retinoid-dependent manner. Identification and functional dissection of promoter elements by transfection and reporter assays PNAS Medium 7831296
1995 A second distinct RA-responsive site in the 3' region of HOXB1 contains a DR-2-type target of the RAR-RXR complex (DR-2B) and a binding site for a distinct RA-dependent coactivator (retinoid-activating protein) with different tissue-specificity from the 5' site, demonstrating two distinct RA response pathways for HOXB1 activation. Identification and functional dissection of a second 3' RARE by reporter assays and binding studies PNAS Medium 7831297
2003 NMR solution structure of the 42-kDa Oct1·Sox2·Hoxb1-DNA ternary complex revealed that Sox2 and the Oct1 POUS domain interact through a predominantly hydrophobic interface surrounded by electrostatic interactions; Sox2 binding locks the POUS domain in a single orientation on DNA, increasing Oct1 site-specific affinity. This provides a mechanism for combinatorial transcriptional control at the Hoxb1 regulatory element. Solution NMR structure determination using residual dipolar couplings and conjoined rigid body/torsion angle dynamics Journal of Biological Chemistry High 14559893
1999 NMR studies showed that the fourth (additional) alpha-helix of Pbx1 is unfolded in solution but folds upon DNA binding; mixing HoxB1 with Pbx1 in the absence of DNA produces no conformational change in Pbx1, suggesting ternary complex assembly requires DNA binding first. Multidimensional NMR spectroscopy (1H, 15N, 13C) of Pbx1 free and DNA-bound, comparison with HoxB1 mixing experiments Journal of Molecular Biology High 10448033
2001 NMR structural analysis showed the HoxB1 hexapeptide adopts a preformed turn structure in solution similar to that seen in the crystal structure of the HoxB1/Pbx1/DNA complex, suggesting the hexapeptide is at least partially prefolded before interaction with Pbx1. NMR structural calculations of hexapeptide of HoxB1 in isolation Protein Science Medium 11369863
1999 Retroviral misexpression of Hoxb1 in a specific rhombomere of chick embryos, combined with orthotopic grafting, caused homeotic transformation of that rhombomere, revealed by reorganization of motor axon projections, demonstrating Hoxb1 specifies rhombomere identity. Retroviral misexpression combined with orthotopic grafting in chick embryos, motor axon projection analysis Science High 10381880
2001 The Hoxb1 autoregulatory enhancer (b1-ARE) contains a bipartite SOX/OCT binding site that confers cell context-specific activity and is required for maximal transcriptional activity of HOX/PBX complexes; HOXB1 has significantly higher transcriptional activity than its paralog HOXA1 due to differences in the HOXB1 N-terminal activation domain; Hoxa1 is the primary mediator of the b1-ARE response to retinoic acid in vivo, dependent on SOX/OCT binding. Reporter assays in embryonal carcinoma cells, domain mapping, transgenic mouse analysis, SOX/OCT site mutagenesis, HOXA1 mutant mouse analysis Journal of Biological Chemistry High 11278854
2005 The Hoxb1 autoregulatory enhancer contains multiple Prep1-Pbx1 (PM) and Pbx1-Hoxb1 (PH) binding sites; a new PM2 site cooperates with R3 (PH site) to form ternary Prep1-Pbx1-Hoxb1 complexes; the R2/PM3 site has high PM binding affinity and acts to inhibit ternary complex formation, thereby restricting reporter expression in transgenic embryos. In vitro binding assays, identification of new binding sites, mutagenesis, transgenic analysis in mouse and chicken embryos Molecular and Cellular Biology High 16166636
2006 Hoxa2 expression in rhombomere 4 is directly regulated by Hoxb1 through three bipartite Hox/Pbx binding sites (PH1-3) and a single Pbx-Prep/Meis (PM) site in a conserved intronic r4 enhancer; the enhancer responds to ectopic HOXB1 expression, placing Hoxa2 downstream of Hoxb1 in the r4 gene regulatory network. Comparative genomics across 12 vertebrate species, in vitro binding studies, mutational analysis, transgenic mouse and chicken analysis, ectopic HOXB1 expression Developmental Biology High 17113575
2000 Hoxb1 controls the specification of progenitor cells along the entire dorsoventral axis of rhombomere 4 by acting early in hindbrain neurogenesis to specify effectors of the sonic hedgehog and Mash1 signaling pathways; in the absence of Hoxb1, multiple neurons normally specified in r4 are programmed for early cell death. Targeted disruption of Hoxb1, analysis of DV patterning markers (Shh and Mash1 pathway effectors), comparison of progenitor populations Development High 11076756
2004 Hoxb1 is required both in facial branchiomotor neurons and in r4-derived neural crest cells (which generate glial cells myelinating the VIIth nerve) for formation and maintenance of the VIIth cranial nerve circuitry; conditional deletion of Hoxb1 in neural crest disrupts glial formation without affecting overall glial progenitor specification, indicating a later glial function. Conditional Cre/loxP deletion of Hoxb1 in neural crest, Cre-lineage analysis, neural crest cell cultures, anatomical analysis Genes & Development High 15198977
2003 In Hoxb1 mutant mice, neurons derived from the presumptive r4 territory are re-specified towards an r2-like identity; motoneurons resemble trigeminal motoneurons in migration patterns and molecular marker expression, demonstrating Hoxb1 is required to maintain r4 identity and prevent r2-like re-specification. Hoxb1, Hoxa1, and Hoxb2 single and compound mutant analysis, molecular marker expression, motoneuron migration patterns, apoptosis pathway manipulation Development High 14522873
2008 Timely induction of Hoxb1 in ESC-derived neural stem cells specifies them toward a hindbrain-specific (r4) identity, represses anterior neural identity, and mediates maintenance and expansion of posterior neural progenitors through activation of the Notch signaling pathway and Notch-dependent STAT3 phosphorylation at Ser 727. Inducible Hoxb1 transgene in ESC differentiation, neural progenitor marker analysis, Notch pathway and JAK/STAT pathway analysis Stem Cells Medium 18499896
2012 A homozygous missense mutation in HOXB1 (Arg207Cys, corresponding to the conserved Arg5 of the homeodomain) in humans causes bilateral facial palsy, hearing loss, and strabismus recapitulating the Hoxb1-/- mouse phenotype; molecular modeling and in vitro DNA-protein binding assays show the mutation disrupts hydrogen bonding and electrostatic interactions with thymine in the DNA minor groove, destabilizing the HOXB1:PBX1:DNA complex and altering HOXB1 transcriptional activity. Human genetic analysis, molecular modeling, in vitro DNA-protein binding assay, structural analysis of homeodomain-DNA contacts American Journal of Human Genetics High 22770981
2011 Hoxb3 directly represses Hoxb1 transcription by binding to a novel site (S3) on the Hoxb1 locus; this was confirmed by EMSA, in vivo ChIP in P19 cells and hindbrain tissues, and chick in ovo luciferase reporter assays showing suppression of Hoxb1 transcriptional activity. EMSA, in vivo ChIP, chick in ovo luciferase reporter assay, gain-of-function transgenic mouse (Hoxb3 driven by Hoxb2 r4 enhancer) Developmental Biology High 21320481
1998 The DR5 RARE (RAIDR5 enhancer) 3' of Hoxb-1 is required for expression in the developing foregut/gut endoderm in transgenic mice; point mutations in the DR5 RARE abolish gut expression without affecting r4 expression, demonstrating tissue-specific RARE function. Transgenic mouse analysis with RARE point mutations and enhancer deletions, lacZ reporter expression analysis Development High 9671595
2015 Hoxb1 deficiency results in a shorter outflow tract and ventricular septal defects; mechanistically, both FGF/ERK and BMP/SMAD signaling (which regulate proliferation and differentiation of cardiac progenitors) are enhanced in the pharyngeal region of Hoxb1 mutants, and absence of Hoxb1 leads to premature myocardial differentiation of second heart field progenitors. Targeted gene knockout, signaling pathway analysis (FGF/ERK and BMP/SMAD), cardiac morphological analysis, compound mutant analysis with Hoxa1 Developmental Biology Medium 26284287
2012 Hoxb1 is required for the anteroposterior identity of rhombomere 4-derived lateral vestibular nucleus (LVN) precursors; loss of Hoxb1 does not alter the glutamatergic phenotype of dB2 neurons but alters their stereotyped spinal cord projection and causes ectopic expression of Lmx1b and Tlx3 at the expense of Phox2a. Hoxb1-GFP reporter mouse, Hoxb1 knockout analysis, retrograde tracing, transcription factor marker analysis PLoS One Medium 22485187
1998 Hoxa1 and Hoxb1 participate in both establishment and maintenance of Hoxb1 expression in r4 through auto- and para-regulatory interactions; the Hoxb1 3' RARE is required for establishing early high levels of Hoxb1 expression; in the absence of both genes, the earliest r4 marker EphA2 fails to be activated, indicating a failure to initiate r4 specification. Double mutant analysis (Hoxa1 null × Hoxb1 3'RARE targeted mutation × Hoxb1 null combinations), molecular marker analysis Development High 9463349
2002 Zebrafish hoxb1a has equivalent function to mouse Hoxb1 in controlling migration of VIIth cranial nerve branchiomotor neurons from r4 posteriorly; RNA rescue experiments show that hoxb1a and hoxb1b (equivalent to mouse Hoxa1) do not have interchangeable biochemical functions—only hoxb1a can properly pattern the VIIth cranial nerve. Morpholino-based knockdown, mRNA rescue experiments, neuroanatomical analysis of VIIth nerve Development High 11973267

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature 515 2571936
1990 Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 474 1975088
1995 Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell 443 7600572
1992 Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development (Cambridge, England) 442 1363087
1994 A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Nature 389 7914354
1996 Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 344 8967950
1993 The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation. Cell 291 8093858
1990 Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development (Cambridge, England) 287 1983472
1991 Introduction of a subtle mutation into the Hox-2.6 locus in embryonic stem cells. Nature 282 1672446
1999 Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation. Cell 279 10052460
1998 Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch. Development (Cambridge, England) 261 9463359
1998 Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning. Development (Cambridge, England) 252 9463349
1994 Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1. Science (New York, N.Y.) 245 7916164
1996 Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development (Cambridge, England) 244 8898234
1992 Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4. Proceedings of the National Academy of Sciences of the United States of America 221 1347944
1991 Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. The EMBO journal 219 1915273
1997 Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Genes & development 171 9242495
1999 Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development (Cambridge, England) 163 10529420
1990 Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and larvae. Cell 163 1979525
2002 Knockdown of duplicated zebrafish hoxb1 genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention. Development (Cambridge, England) 155 11973267
1992 Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions. Nature 151 1545869
1988 Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene. Genes & development 143 2463210
2003 Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex. The Journal of biological chemistry 132 14559893
1989 Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic acids research 130 2564662
1999 Homeotic transformation of rhombomere identity after localized Hoxb1 misexpression. Science (New York, N.Y.) 120 10381880
1996 Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4. Development (Cambridge, England) 120 9012503
1992 Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions in the nervous system and the potential for shared regulatory regions. The EMBO journal 118 1582411
2000 Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology 110 11091361
2006 Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 109 16823611
1990 Hox-2.3 upstream sequences mediate lacZ expression in intermediate mesoderm derivatives of transgenic mice. Development (Cambridge, England) 105 1977573
1991 The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development. Development (Cambridge, England) 100 1685115
1991 The expression of murine Hox-2 genes is dependent on the differentiation pathway and displays a collinear sensitivity to retinoic acid in F9 cells and Xenopus embryos. Nucleic acids research 99 1682879
1993 Conditional immortalization of mouse myelomonocytic, megakaryocytic and mast cell progenitors by the Hox-2.4 homeobox gene. The EMBO journal 97 8104786
2003 Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes. Development (Cambridge, England) 94 14522873
1998 A conserved retinoic acid responsive element in the murine Hoxb-1 gene is required for expression in the developing gut. Development (Cambridge, England) 94 9671595
1998 An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins. The Journal of biological chemistry 91 9733765
2001 Synergy between Hoxa1 and Hoxb1: the relationship between arch patterning and the generation of cranial neural crest. Development (Cambridge, England) 89 11532923
1999 The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4. Development (Cambridge, England) 87 10556076
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