Gene Symbol: Hoxb4
Description: homeobox B4
Alias: Hox-2.6, homeobox protein Hox-B4, homeo box B4, homeobox protein Hox-2.6
Species: mouse
Products:     Hoxb4

Top Publications

  1. Brend T, Gilthorpe J, Summerbell D, Rigby P. Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression. Development. 2003;130:2717-28 pubmed
    ..In this study, we demonstrate that expression of Hoxb4 in the paraxial mesoderm of the mouse embryo is transcriptionally regulated in several distinct phases, and that ..
  2. Graham A, Maden M, Krumlauf R. The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development. Development. 1991;112:255-64 pubmed
    ..This suggests that, while genes in the different murine Hox clusters may have similar A-P domains of expression, they are responding to different dorsoventral patterning signals in the developing spinal cord. ..
  3. Graham A, Papalopulu N, Lorimer J, McVey J, Tuddenham E, Krumlauf R. Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene. Genes Dev. 1988;2:1424-38 pubmed
    ..The patterns of Hox-2.6 expression in both mesoderm and ectoderm are spatially restricted and may reflect a role for the gene in the response to or establishment of positional cues in the embryo. ..
  4. Bijl J, Thompson A, Ramirez Solis R, Krosl J, Grier D, Lawrence H, et al. Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells. Blood. 2006;108:116-22 pubmed
    Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell (HSC) populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program that determines self-renewal...
  5. Gaunt S, Krumlauf R, Duboule D. 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. 1989;107:131-41 pubmed
    ..We also propose how our new findings may help to explain any selective advantage to the vertebrates of homeo-gene duplication to form subfamilies. ..
  6. Conlon R, Rossant J. Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development. 1992;116:357-68 pubmed
  7. Sadl V, Sing A, Mar L, Jin F, Cordes S. Analysis of hindbrain patterning defects caused by the kreisler(enu) mutation reveals multiple roles of Kreisler in hindbrain segmentation. Dev Dyn. 2003;227:134-42 pubmed
    ..Hence, Kreisler regulates maintenance and expansion of r5 and specification of r6 but is not required for r3 development. ..
  8. Manzanares M, Trainor P, Nonchev S, Ariza McNaughton L, Brodie J, Gould A, et al. The role of kreisler in segmentation during hindbrain development. Dev Biol. 1999;211:220-37 pubmed
    ..We conclude that the mouse kreisler gene regulates multiple steps in segmental patterning involving both the formation of segments and their A-P identity. ..
  9. Gould A, Morrison A, Sproat G, White R, Krumlauf R. Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns. Genes Dev. 1997;11:900-13 pubmed
    ..During mouse hindbrain development, Hoxb3 and Hoxb4 share an expression domain caudal to the boundary between rhombomeres 6 and 7...

More Information


  1. Barrow J, Capecchi M. Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4. Development. 1996;122:3817-28 pubmed
    ..Hoxb-2 and hoxb-4 appear to function together to mediate proper closure of the ventral thoracic body wall. Failure in this closure results in severe defects of the sternum. ..
  2. Brun A, Bjornsson J, Magnusson M, Larsson N, Leveen P, Ehinger M, et al. Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. Blood. 2004;103:4126-33 pubmed
    Enforced expression of Hoxb4 dramatically increases the regeneration of murine hematopoietic stem cells (HSCs) after transplantation and enhances the repopulation ability of human severe combined immunodeficiency (SCID) repopulating ..
  3. Gutman A, Gilthorpe J, Rigby P. Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4. Mol Cell Biol. 1994;14:8143-54 pubmed
    ..The complex architecture of the Hoxb-4 promoter provides the framework for fine-tuned transcriptional regulation during embryonic development. ..
  4. Whiting J, Marshall H, Cook M, Krumlauf R, Rigby P, Stott D, et al. Multiple spatially specific enhancers are required to reconstruct the pattern of Hox-2.6 gene expression. Genes Dev. 1991;5:2048-59 pubmed
    ..The definition of such elements will allow the characterization of the trans-acting factors that mediate spatial regulation in the mammalian embryo. ..
  5. Bijl J, Krosl J, Lebert Ghali C, Vacher J, Mayotte N, Sauvageau G. Evidence for Hox and E2A-PBX1 collaboration in mouse T-cell leukemia. Oncogene. 2008;27:6356-64 pubmed publisher
    ..Results presented in this report show that the onset of T-cell leukemia is significantly accelerated in E2A-PBX1 x Hoxb4 compound transgenic animals when compared with control E2A-PBX1 or Hoxb4 littermates...
  6. Frohman M, Martin G, Cordes S, Halamek L, Barsh G. Altered rhombomere-specific gene expression and hyoid bone differentiation in the mouse segmentation mutant, kreisler (kr). Development. 1993;117:925-36 pubmed
  7. Serpente P, Tümpel S, Ghyselinck N, Niederreither K, Wiedemann L, Dolle P, et al. Direct crossregulation between retinoic acid receptor {beta} and Hox genes during hindbrain segmentation. Development. 2005;132:503-13 pubmed
    ..border that regresses until, at later stages, it is stably maintained at the r6/r7 boundary by inputs from Hoxb4 and Hoxd4...
  8. Faubert A, Chagraoui J, Mayotte N, Frechette M, Iscove N, Humphries R, et al. Complementary and independent function for Hoxb4 and Bmi1 in HSC activity. Cold Spring Harb Symp Quant Biol. 2008;73:555-64 pubmed publisher
    ..we investigated possible genetic interactions between two well-recognized regulators of this process: Bmi1 and Hoxb4. Using complementation and overexpression strategies in mouse HSCs, we document that Bmi1 is not required for the ..
  9. Landsberg R, Awatramani R, Hunter N, Farago A, DiPietrantonio H, Rodriguez C, et al. Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6. Neuron. 2005;48:933-47 pubmed
    ..These studies suggest that underlying the diversity and proportions of fates produced by the LRL is a precise suborganization regulated by Pax6. ..
  10. Dupé V, Ghyselinck N, Wendling O, Chambon P, Mark M. Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse. Development. 1999;126:5051-9 pubmed
  11. Milsom M, Schiedlmeier B, Bailey J, Kim M, Li D, Jansen M, et al. Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-{alpha} on Fanconi anemia hematopoietic stem and progenitor cells. Blood. 2009;113:5111-20 pubmed publisher
    Ectopic delivery of HOXB4 elicits the expansion of engrafting hematopoietic stem cells (HSCs). We hypothesized that inhibition of tumor necrosis factor-alpha (TNF-alpha) signaling may be central to the self-renewal signature of HOXB4...
  12. Folberg A, Kovács E, Huang H, Houle M, Lohnes D, Featherstone M. Hoxd4 and Rarg interact synergistically in the specification of the cervical vertebrae. Mech Dev. 1999;89:65-74 pubmed
    ..Somitic expression of Hoxd4 is not altered in wild-type or Rarg mutant animals before or after RA treatment on day 10.5, suggesting that Hoxd4 and Rarg act in parallel to regulate the expression of target genes directing skeletogenesis. ..
  13. Giannola D, Shlomchik W, Jegathesan M, Liebowitz D, Abrams C, Kadesch T, et al. Hematopoietic expression of HOXB4 is regulated in normal and leukemic stem cells through transcriptional activation of the HOXB4 promoter by upstream stimulating factor (USF)-1 and USF-2. J Exp Med. 2000;192:1479-90 pubmed
    ..Since HOXB4 plays a key role in regulating the balance between hematopoietic stem cell renewal and differentiation, we studied ..
  14. Neijts R, Amin S, van Rooijen C, Deschamps J. Cdx is crucial for the timing mechanism driving colinear Hox activation and defines a trunk segment in the Hox cluster topology. Dev Biol. 2017;422:146-154 pubmed publisher
    ..Subsequently to initial Wnt-induced activation of 3' Hox genes, Cdx transcription factors would act as crucial effectors for activating central Hox genes, until the last gene of the cluster arrests the process. ..
  15. Madan V, Madan B, Brykczynska U, Zilbermann F, Hogeveen K, Dohner K, et al. Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog MLL5. Blood. 2009;113:1444-54 pubmed publisher
    ..Together, these in vivo findings establish several nonredundant functions for Mll5, including an essential role in regulating proliferation and functional integrity of hematopoietic stem/progenitor cells. ..
  16. Deschamps J, van Nes J. Developmental regulation of the Hox genes during axial morphogenesis in the mouse. Development. 2005;132:2931-42 pubmed
    ..In particular, we highlight the integration of these transducers of anteroposterior positional information into the genetic network that drives tissue generation and patterning during axial elongation. ..
  17. van Rooijen C, Simmini S, Bialecka M, Neijts R, van de Ven C, Beck F, et al. Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence. Development. 2012;139:2576-83 pubmed publisher
    ..Cdx requirement for the post-head section of the axis is ancestral as it takes place in arthropods as well. ..
  18. Yagi H, Deguchi K, Aono A, Tani Y, Kishimoto T, Komori T. Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice. Blood. 1998;92:108-17 pubmed
    ..These data show that the hematopoietic precursors were greatly reduced in mutant mice, and suggest that Mll functions as a regulator of the growth of hematopoietic precursors. ..
  19. Kyba M, Perlingeiro R, Daley G. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell. 2002;109:29-37 pubmed
    ..progenitors derived from yolk sac or embryonic stem (ES) cells, we examined the effect of ectopic expression of HoxB4, a homeotic selector gene implicated in self-renewal of definitive HSCs...
  20. Gordon Keylock S, Jackson M, Huang C, Samuel K, Axton R, Oostendorp R, et al. Induction of hematopoietic differentiation of mouse embryonic stem cells by an AGM-derived stromal cell line is not further enhanced by overexpression of HOXB4. Stem Cells Dev. 2010;19:1687-98 pubmed publisher
    ..co-culture with stromal cells derived from hematopoietic tissues and by overexpression of the transcription factor HOXB4. In this study, we compare the hematopoietic inductive effects of stromal cell lines derived from different ..
  21. Liang S, Moghimi B, Crusselle Davis V, Lin I, Rosenberg M, Li X, et al. Defective erythropoiesis in transgenic mice expressing dominant-negative upstream stimulatory factor. Mol Cell Biol. 2009;29:5900-10 pubmed publisher
    ..Previous work demonstrated that USF regulates genes during erythroid differentiation, including HoxB4 and beta-globin...
  22. Kirito K, Fox N, Kaushansky K. Thrombopoietin stimulates Hoxb4 expression: an explanation for the favorable effects of TPO on hematopoietic stem cells. Blood. 2003;102:3172-8 pubmed
    ..To explore the molecular basis of this effect, we postulated that Hoxb4 might mediate at least part of the TPO effect on these cells...
  23. Luo J, Pasceri P, Conlon R, Rossant J, Giguere V. Mice lacking all isoforms of retinoic acid receptor beta develop normally and are susceptible to the teratogenic effects of retinoic acid. Mech Dev. 1995;53:61-71 pubmed
    ..These experiments demonstrate that RAR beta isoforms are not absolutely required for embryonic development and provide additional support to the concept of functional redundancy among members of the RAR family. ..
  24. di Meglio T, Kratochwil C, Vilain N, Loche A, Vitobello A, Yonehara K, et al. Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons. Science. 2013;339:204-7 pubmed publisher
    ..Thus, Ezh2-dependent epigenetic regulation of intrinsic and extrinsic transcriptional programs controls topographic neuronal guidance and connectivity in the cortico-ponto-cerebellar pathway. ..
  25. Minoux M, Antonarakis G, Kmita M, Duboule D, Rijli F. Rostral and caudal pharyngeal arches share a common neural crest ground pattern. Development. 2009;136:637-45 pubmed publisher
    ..These results provide insights into how facial and throat structures are assembled during development, and have implications for the evolution of the pharyngeal region of the vertebrate head. ..
  26. Yu H, Neale G, Zhang H, Lee H, Ma Z, Zhou S, et al. Downregulation of Prdm16 mRNA is a specific antileukemic mechanism during HOXB4-mediated HSC expansion in vivo. Blood. 2014;124:1737-47 pubmed publisher
    Overexpression of HOXB4 in hematopoietic stem cells (HSCs) leads to increased self-renewal without causing hematopoietic malignancies in transplanted mice...
  27. Tabayoyong W, Salas J, Bonde S, Zavazava N. HOXB4-transduced embryonic stem cell-derived Lin-c-kit+ and Lin-Sca-1+ hematopoietic progenitors express H60 and are targeted by NK cells. J Immunol. 2009;183:5449-57 pubmed publisher
    ..we demonstrate that hematopoietic progenitor cells (HPCs) derived from mouse ES cells ectopically expressing HOXB4 fail to engraft long-term in the presence of NK cells...
  28. Schmittwolf C, Porsch M, Greiner A, Avots A, Müller A. HOXB4 confers a constant rate of in vitro proliferation to transduced bone marrow cells. Oncogene. 2005;24:561-72 pubmed
    b>HOXB4 overexpression mediates increased self-renewal of haematopoietic stem cells (HSCs) ex vivo...
  29. Yasunaga S, Ohtsubo M, Ohno Y, Saeki K, Kurogi T, Tanaka Okamoto M, et al. Scmh1 has E3 ubiquitin ligase activity for geminin and histone H2A and regulates geminin stability directly or indirectly via transcriptional repression of Hoxa9 and Hoxb4. Mol Cell Biol. 2013;33:644-60 pubmed publisher
    ..Loss of Scmh1 caused derepression of Hoxb4 and Hoxa9, direct targets of PcG complex 1-mediated transcriptional silencing in hematopoietic cells...
  30. Frison H, Giono G, Thebault P, Fournier M, Labrecque N, Bijl J. Hoxb4 overexpression in CD4 memory phenotype T cells increases the central memory population upon homeostatic proliferation. PLoS ONE. 2013;8:e81573 pubmed publisher
    ..The transcription factor Hoxb4 has been shown to promote self-renewal divisions of hematopoietic stem cells resulting in an expansion of these ..
  31. Schwarz D, Varum S, Zemke M, Schöler A, Baggiolini A, Draganova K, et al. Ezh2 is required for neural crest-derived cartilage and bone formation. Development. 2014;141:867-77 pubmed publisher
    ..Our data indicate that craniofacial skeleton formation in higher vertebrates is crucially dependent on epigenetic regulation that keeps in check inhibitors of an osteochondrogenic differentiation program. ..
  32. Lengerke C, McKinney Freeman S, Naveiras O, Yates F, Wang Y, Bansal D, et al. The cdx-hox pathway in hematopoietic stem cell formation from embryonic stem cells. Ann N Y Acad Sci. 2007;1106:197-208 pubmed
    ..We show here that brief pulses of ectopic Cdx4 or HoxB4 expression are sufficient to enhance hematopoiesis during ESC differentiation, presumably by acting as ..
  33. Wilkinson D, Bhatt S, Cook M, Boncinelli E, Krumlauf R. Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature. 1989;341:405-9 pubmed
    ..These data indicate that Hox genes specify segment phenotype, a role analogous to that of their Drosophila homologues. ..
  34. Horan G, Ramirez Solis R, Featherstone M, Wolgemuth D, Bradley A, Behringer R. Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed. Genes Dev. 1995;9:1667-77 pubmed
  35. Park I, Qian D, Kiel M, Becker M, Pihalja M, Weissman I, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302-5 pubmed
    ..Expression of p16Ink4a and p19Arf in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs. ..
  36. Boulet A, Capecchi M. Targeted disruption of hoxc-4 causes esophageal defects and vertebral transformations. Dev Biol. 1996;177:232-49 pubmed
    ..Therefore, this mutation is likely to cause a reduction of hoxc-5 function as well as complete loss of hoxc-4 function. ..
  37. Sham M, Hunt P, Nonchev S, Papalopulu N, Graham A, Boncinelli E, et al. 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. EMBO J. 1992;11:1825-36 pubmed
    ..6 gene and the expression of transgenic and endogenous transcripts in a Hox-2.8 pattern, suggest that regulatory elements may be shared by neighbouring genes to establish the complete expression pattern. ..
  38. Pilon N, Oh K, Sylvestre J, Savory J, Lohnes D. Wnt signaling is a key mediator of Cdx1 expression in vivo. Development. 2007;134:2315-23 pubmed
    ..As Wnt signaling is implicated in somitogenesis upstream of the Notch pathway, it is conceivable that Cdx1 might play a role in this process. However, none of the Notch pathway genes assessed was overtly affected. ..
  39. Hunt P, Wilkinson D, Krumlauf R. Patterning the vertebrate head: murine Hox 2 genes mark distinct subpopulations of premigratory and migrating cranial neural crest. Development. 1991;112:43-50 pubmed
  40. Ahn Y, Mullan H, Krumlauf R. Long-range regulation by shared retinoic acid response elements modulates dynamic expression of posterior Hoxb genes in CNS development. Dev Biol. 2014;388:134-44 pubmed publisher
    ..Our data demonstrate that multiple RAREs cooperate to remotely regulate 5? Hoxb genes during CNS development, providing a new insight into the mechanisms for gene regulation within the Hox clusters. ..
  41. Bentley K, Bradshaw M, Ruddle F. Physical linkage of the murine Hox-b cluster and nerve growth factor receptor on yeast artificial chromosomes. Genomics. 1993;18:43-53 pubmed
    ..These clones confirm the pulsed-field restriction map of uncloned mouse DNA and represent a contig of approximately 600 kb of cloned material from mouse chromosomes 11. ..
  42. Jackson M, Axton R, Taylor A, Wilson J, Gordon Keylock S, Kokkaliaris K, et al. HOXB4 can enhance the differentiation of embryonic stem cells by modulating the hematopoietic niche. Stem Cells. 2012;30:150-60 pubmed publisher
    ..development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells (HPCs) where it promotes self-renewal, but it is also ..
  43. Fleury M, Petit Cocault L, Clay D, Souyri M. Mpl receptor defect leads to earlier appearance of hematopoietic cells/hematopoietic stem cells in the Aorta-Gonad-Mesonephros region, with increased apoptosis. Int J Dev Biol. 2010;54:1067-74 pubmed publisher
    ..formation of hematopoietic progenitor (HP) cells and HSCs from the vasculature, as well as expression of Meis1 and HoxB4, known to play a role in self-renewal and expansion of HSCs, were found to be down regulated in E10.5 Mpl-/- AGMs...
  44. Ikeya M, Takada S. Wnt-3a is required for somite specification along the anteroposterior axis of the mouse embryo and for regulation of cdx-1 expression. Mech Dev. 2001;103:27-33 pubmed
    ..These results indicate that Wnt-3a is necessary for correct anteroposterior patterning of vertebra, and that cdx-1 may be one of the mediator genes of Wnt-3a signaling in this process. ..
  45. Savory J, Pilon N, Grainger S, Sylvestre J, Béland M, Houle M, et al. Cdx1 and Cdx2 are functionally equivalent in vertebral patterning. Dev Biol. 2009;330:114-22 pubmed publisher
  46. Isono K, Mizutani Koseki Y, Komori T, Schmidt Zachmann M, Koseki H. Mammalian polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1. Genes Dev. 2005;19:536-41 pubmed
    ..Importantly, the levels of Sf3b1 in PcG complexes were decreased in Sf3b1-heterozygous embryos. These findings suggest that Sf3b1-PcG protein interaction is essential for true PcG-mediated repression of Hox genes. ..
  47. Guris D, Duester G, Papaioannou V, Imamoto A. Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Dev Cell. 2006;10:81-92 pubmed
    ..Thus, we suggest that del22q11 is a contiguous gene syndrome involving dose-sensitive interaction of CRKL and TBX1 and locally aberrant RA signaling. ..
  48. Medina Martinez O, Bradley A, Ramirez Solis R. A large targeted deletion of Hoxb1-Hoxb9 produces a series of single-segment anterior homeotic transformations. Dev Biol. 2000;222:71-83 pubmed
    ..Thus, Hoxb13 expression seems to be independent of the deleted region, suggesting that its expression pattern could be achieved independent of the colinear pattern of the cluster or by a regulatory element located 5' of Hoxb9. ..
  49. McKinney Freeman S, Naveiras O, Yates F, Loewer S, Philitas M, Curran M, et al. Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells. Blood. 2009;114:268-78 pubmed publisher
    ..The prospective fractionation of ESC-HSCs will facilitate studies of HSC maturation essential for normal functional engraftment in irradiated adults. ..
  50. Gaufo G, Thomas K, Capecchi M. Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motoneurons. Development. 2003;130:5191-201 pubmed
  51. Hong S, Yang S, Kim T, Shim J, Lee H, Lee G, et al. Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem cells: a model of molecular convergence for stemness. Stem Cells. 2014;32:1313-22 pubmed publisher
    The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells (HSCs) without overriding the normal stem cell pool size...
  52. Graham A, Papalopulu N, Krumlauf R. The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell. 1989;57:367-78 pubmed
    ..Our results argue that these complexes arose from a common ancestor, present before the divergence of lineages that gave rise to arthropods and vertebrates. ..
  53. Pilat S, Carotta S, Schiedlmeier B, Kamino K, Mairhofer A, Will E, et al. HOXB4 enforces equivalent fates of ES-cell-derived and adult hematopoietic cells. Proc Natl Acad Sci U S A. 2005;102:12101-6 pubmed
    ..and differentiation properties of adult bone marrow cells, in vitro and in vivo, when ectopically expressing HOXB4. Myeloid development was enforced and (T) lymphoid development suppressed over a wide range of expression levels, ..