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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review

Hoxb1  -  homeobox B1

Mus musculus

Synonyms: Homeobox protein Hox-2.9, Homeobox protein Hox-B1, Hox-2.9, Hoxb-1
 
 
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Disease relevance of Hoxb1

  • In addition, our transgenic data indicate that the Hoxb1 gene is expressed in other tissues such as the hernia gut, genital eminence, and lung [1].
  • We show that, in P19 embryonal carcinoma cells, GCs potentiate RA-induced expression of the murine Hoxb -1 gene through an autoregulatory element, b1-ARE, recognized by the Pbx1 and HOXB1 homoeodomain proteins [2].
 

High impact information on Hoxb1

  • Comparison of Hoxb-1 regulatory regions from different vertebrates identified three related sequence motifs critical for rhombomere 4 (r4) expression in the hindbrain [3].
  • These results demonstrate that, as a part of its role in maintaining rhombomere identity, Hoxb-1 is involved in controlling migratory properties of motor neurons in the hindbrain [4].
  • Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1 [4].
  • We have now identified two enhancers, 3' of the mouse Hoxb-1 gene, which together reconstruct the early endogenous expression pattern and mediate the early ectopic response to retinoic acid [5].
  • Therefore, this RARE is not only involved in the ectopic response to retinoic acid, but is also essential for establishing aspects of the early Hoxb-1 expression pattern [5].
 

Biological context of Hoxb1

  • The Hoxb1 autoregulatory enhancer directs segmental expression in vertebrate hindbrain [6].
  • The Hoxa1 mutant phenotype is consistent with a partial misspecification of the presumptive r4 territory that results from partial Hoxb1 activation [7].
  • Hoxb1 expression requires 3' and 5' RA response elements for widespread induction up to r4 and for r3/r5 repression, but RA has previously been detected only from r5-r8, and vHnf1 is required for repression of Hoxb1 posterior to r4 in zebrafish [8].
  • In contrast, the RA-responding Hoxb1lacZ transgene that faithfully mimics the endogenous gene (Marshall et al., 1994) did not exhibit the sensitivity of Hoxb1 to precocious activation [9].
  • In contrast, transcripts encoding Hoxb-1 (Hox-2.9) and cellular RA binding protein II (CRABPII) are activated by RA for a longer period of time in the RAR gamma-/- lines compared to the wild-type F9 line [10].
 

Anatomical context of Hoxb1

  • On the basis of these experiments we conclude that the r4-restricted domain of Hoxb2 in the hindbrain is the result of a direct cross-regulatory interaction by Hoxb1 involving vertebrate Pbx proteins as cofactors [11].
  • We show that, already before primitive streak formation, prior to initial expression of the first Hox gene, a dramatic transcriptional stimulation of the 3'most genes, Hoxb1 and Hoxb2, is observed upon a short pulse of exogenous retinoic acid (RA), whereas it is not in the case for more 5', cluster-internal, RA-responsive Hoxb genes [9].
  • Additionally, alterations in the pattern of Hoxa-2 and Hoxb-1 expression in a subpopulation of neural crest cells migrating from the rhombomere 2 region are detected in these transgenics [12].
  • Neurofilament staining and retrograde labelling of motor neurons indicated that Hoxa1 and Hoxb1 synergise in patterning the VIIth through XIth cranial nerves [13].
  • Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch [13].
 

Associations of Hoxb1 with chemical compounds

 

Regulatory relationships of Hoxb1

  • Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1 [11].
  • Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways [17].
  • In addition, we found that PIASxbeta is able to activate the r4-specific gene Hoxb1 [18].
 

Other interactions of Hoxb1

  • This suggests that part of the functional role of Hoxb1 in maintaining r4 identity may be mediated by the Hoxb2 gene [11].
  • Failure to express Hoxb1 to this boundary in Hoxa1 mutant embryos initiates a cascade of gene misexpressions that result in misspecification of the hindbrain compartments from r2 through r5 [19].
  • The expression domain of Hoxb-1 is affected differently from the other genes in kr/kr embryos; its rostral boundary at r3/4 is intact but the caudal boundary is displaced from its normal location at r4/5 to the approximate position of r5/6 [20].
  • However, no obvious alterations in the spatial pattern of expression of Hoxb-1, Hoxb-4 and Hoxb-5 were observed in day 9.5 p.c. embryos [21].
  • After Hoxb1 induction, the RA boundary quickly shifts to r4/r5, coincident with induction of Cyp26c1 in r4 [8].
 

Analytical, diagnostic and therapeutic context of Hoxb1

  • Using whole mount in situ hybridization and immunohistochemistry, we studied the expression of Hoxb-1, b-2, b-3, b-4 and b-5 in the E9.5-E14.5 foreguts and lungs [22].
  • Hoxb1, which is expressed throughout rhombomere 4 (r4), has been shown to be required for the specification of facial branchiomotor neuron progenitors that are programmed to innervate the muscles of facial expression [23].
  • The amount of individual Hox gene message varies considerably, but expression of all genes is detectable by RNase protection except Hoxb-1, which could not be detected even by the reverse transcription-polymerase chain reaction (RT-PCR) assay [24].

References

  1. Analysis of two distinct retinoic acid response elements in the homeobox gene Hoxb1 in transgenic mice. Huang, D., Chen, S.W., Gudas, L.J. Dev. Dyn. (2002) [Pubmed]
  2. Cross-talk between glucocorticoid and retinoic acid signals involving glucocorticoid receptor interaction with the homoeodomain protein Pbx1. Subramaniam, N., Campión, J., Rafter, I., Okret, S. Biochem. J. (2003) [Pubmed]
  3. Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Pöpperl, H., Bienz, M., Studer, M., Chan, S.K., Aparicio, S., Brenner, S., Mann, R.S., Krumlauf, R. Cell (1995) [Pubmed]
  4. Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Studer, M., Lumsden, A., Ariza-McNaughton, L., Bradley, A., Krumlauf, R. Nature (1996) [Pubmed]
  5. A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Marshall, H., Studer, M., Pöpperl, H., Aparicio, S., Kuroiwa, A., Brenner, S., Krumlauf, R. Nature (1994) [Pubmed]
  6. Hoxb1 enhancer and control of rhombomere 4 expression: complex interplay between PREP1-PBX1-HOXB1 binding sites. Ferretti, E., Cambronero, F., Tümpel, S., Longobardi, E., Wiedemann, L.M., Blasi, F., Krumlauf, R. Mol. Cell. Biol. (2005) [Pubmed]
  7. Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes. Gavalas, A., Ruhrberg, C., Livet, J., Henderson, C.E., Krumlauf, R. Development (2003) [Pubmed]
  8. Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression. Sirbu, I.O., Gresh, L., Barra, J., Duester, G. Development (2005) [Pubmed]
  9. Hox cluster polarity in early transcriptional availability: a high order regulatory level of clustered Hox genes in the mouse. Roelen, B.A., de Graaff, W., Forlani, S., Deschamps, J. Mech. Dev. (2002) [Pubmed]
  10. Loss of retinoic acid receptor gamma function in F9 cells by gene disruption results in aberrant Hoxa-1 expression and differentiation upon retinoic acid treatment. Boylan, J.F., Lohnes, D., Taneja, R., Chambon, P., Gudas, L.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  11. Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Maconochie, M.K., Nonchev, S., Studer, M., Chan, S.K., Pöpperl, H., Sham, M.H., Mann, R.S., Krumlauf, R. Genes Dev. (1997) [Pubmed]
  12. Ectopic Hoxa-1 induces rhombomere transformation in mouse hindbrain. Zhang, M., Kim, H.J., Marshall, H., Gendron-Maguire, M., Lucas, D.A., Baron, A., Gudas, L.J., Gridley, T., Krumlauf, R., Grippo, J.F. Development (1994) [Pubmed]
  13. Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch. Gavalas, A., Studer, M., Lumsden, A., Rijli, F.M., Krumlauf, R., Chambon, P. Development (1998) [Pubmed]
  14. Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick. Roberts, C., Ivins, S., Cook, A.C., Baldini, A., Scambler, P.J. Hum. Mol. Genet. (2006) [Pubmed]
  15. Postimplantation mouse embryos cultured in vitro. Assessment with whole-mount immunostaining and in situ hybridization. Van Maele-Fabry, G., Clotman, F., Gofflot, F., Bosschaert, J., Picard, J.J. Int. J. Dev. Biol. (1997) [Pubmed]
  16. MEIS C termini harbor transcriptional activation domains that respond to cell signaling. Huang, H., Rastegar, M., Bodner, C., Goh, S.L., Rambaldi, I., Featherstone, M. J. Biol. Chem. (2005) [Pubmed]
  17. Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Gaufo, G.O., Flodby, P., Capecchi, M.R. Development (2000) [Pubmed]
  18. PIASxbeta acts as an activator of Hoxb1 and is antagonized by Krox20 during hindbrain segmentation. Garcia-Dominguez, M., Gilardi-Hebenstreit, P., Charnay, P. EMBO J. (2006) [Pubmed]
  19. Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Barrow, J.R., Stadler, H.S., Capecchi, M.R. Development (2000) [Pubmed]
  20. Altered rhombomere-specific gene expression and hyoid bone differentiation in the mouse segmentation mutant, kreisler (kr). Frohman, M.A., Martin, G.R., Cordes, S.P., Halamek, L.P., Barsh, G.S. Development (1993) [Pubmed]
  21. Mice lacking all isoforms of retinoic acid receptor beta develop normally and are susceptible to the teratogenic effects of retinoic acid. Luo, J., Pasceri, P., Conlon, R.A., Rossant, J., Giguère, V. Mech. Dev. (1995) [Pubmed]
  22. Expression of Hoxb genes in the developing mouse foregut and lung. Bogue, C.W., Lou, L.J., Vasavada, H., Wilson, C.M., Jacobs, H.C. Am. J. Respir. Cell Mol. Biol. (1996) [Pubmed]
  23. Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry. Arenkiel, B.R., Tvrdik, P., Gaufo, G.O., Capecchi, M.R. Genes Dev. (2004) [Pubmed]
  24. Expression of class I homeobox genes in fetal and adult murine skin. Detmer, K., Lawrence, H.J., Largman, C. J. Invest. Dermatol. (1993) [Pubmed]
 
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