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Gene Review

Hoxa1  -  homeobox A1

Mus musculus

Synonyms: ERA1, Early retinoic acid 1, Era-1, Homeobox protein Hox-1.6, Homeobox protein Hox-A1, ...
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Disease relevance of Hoxa1

  • Unexpectedly, in Hoxa1/Hoxa2 double mutants, the penetrance of cleft palate is dramatically reduced [1].
  • We have previously identified a 10 bp element, called CE2, which is located approximately 3 kilobases 3' of the Hoxa1 coding region in the RAIDR5 enhancer, and which binds to an approximately 170 kd protein in retinoic acid treated P19 embryonal carcinoma cells [2].
  • We previously identified a 3' enhancer called the RAIDR5, which contained a DR5 retinoic acid response element (RARE) and was responsible for the retinoic acid (RA)-associated expression of the murine Hoxa-1 gene in teratocarcinoma cells [3].
  • Of all common integration sites, a small region of 19 kb in the Hoxa gene locus, mostly between Hoxa6 and Hoxa10, represented 18% of all integrations in the E2a-PBX1 B-cell leukemia and was targeted in 86% of these leukemias compared to 17% in control tumors [4].

High impact information on Hoxa1


Biological context of Hoxa1


Anatomical context of Hoxa1

  • Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse [11].
  • Two of these genes, Hoxa1 and Hoxa2, have been shown to be required for proper patterning of the early mouse hindbrain and the associated neural crest [11].
  • We have generated Hoxa1(-/-) embryonic stem (ES) cells (named Hoxa1-15) from Hoxa1(-/-) mutant blastocysts to study the Hoxa1 signaling pathway [8].
  • While no obvious change in the morphology of the trigeminal or facial-acoustic ganglia is evident, phenotypic changes do occur in neurons that emanate from rhombomeres 2 and 3 in the Hoxa-1 transgenic embryos [10].
  • GFP expression in the foregut pocket of Hoxa1(GFPneo) embryos suggests a role for Hoxa1 in foregut-mediated differentiation of the cardiogenic mesoderm [12].

Associations of Hoxa1 with chemical compounds

  • Interestingly, we also find that the Hoxa-1 expression response to RA treatment is not entirely controlled by the RARE, suggesting the existence of other retinoid-induced factors mediating the Hoxa-1 response to RA and/or the presence of additional RAREs [13].

Physical interactions of Hoxa1


Regulatory relationships of Hoxa1


Other interactions of Hoxa1

  • 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 [11].
  • Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes [7].
  • Here, we show that the fluorescent signals produced by single-copy, targeted GFP in-frame fusions with two different murine Hox genes, Hoxa1 and Hoxc13, are readily detectable by using confocal microscopy [12].
  • In E8.0-8.5 Hoxa-1 mutants, cad6 expression was suppressed in the region of rhombomeres 4 to 6, although that in the other regions was not essentially affected [16].
  • The set of defects associated with the disruption of Hox-1.6 is distinct from and nonoverlapping with that of the closely linked Hox-1.5 gene [17].

Analytical, diagnostic and therapeutic context of Hoxa1


  1. Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants. Barrow, J.R., Capecchi, M.R. Development (1999) [Pubmed]
  2. An evolutionary conserved element is essential for somite and adjacent mesenchymal expression of the Hoxa1 gene. Thompson, J.R., Chen, S.W., Ho, L., Langston, A.W., Gudas, L.J. Dev. Dyn. (1998) [Pubmed]
  3. Retinoic acid-responsive enhancers located 3' of the Hox A and Hox B homeobox gene clusters. Functional analysis. Langston, A.W., Thompson, J.R., Gudas, L.J. J. Biol. Chem. (1997) [Pubmed]
  4. High incidence of proviral integrations in the Hoxa locus in a new model of E2a-PBX1-induced B-cell leukemia. Bijl, J., Sauvageau, M., Thompson, A., Sauvageau, G. Genes Dev. (2005) [Pubmed]
  5. Retinoic acid rescues inner ear defects in Hoxa1 deficient mice. Pasqualetti, M., Neun, R., Davenne, M., Rijli, F.M. Nat. Genet. (2001) [Pubmed]
  6. Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Lufkin, T., Dierich, A., LeMeur, M., Mark, M., Chambon, P. Cell (1991) [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. Differences in gene expression between wild type and Hoxa1 knockout embryonic stem cells after retinoic acid treatment or leukemia inhibitory factor (LIF) removal. Martinez-Ceballos, E., Chambon, P., Gudas, L.J. J. Biol. Chem. (2005) [Pubmed]
  9. Local alterations of Krox-20 and Hox gene expression in the hindbrain suggest lack of rhombomeres 4 and 5 in homozygote null Hoxa-1 (Hox-1.6) mutant embryos. Dollé, P., Lufkin, T., Krumlauf, R., Mark, M., Duboule, D., Chambon, P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  10. 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]
  11. 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]
  12. Detection of targeted GFP-Hox gene fusions during mouse embryogenesis. Godwin, A.R., Stadler, H.S., Nakamura, K., Capecchi, M.R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  13. In vivo functional analysis of the Hoxa-1 3' retinoic acid response element (3'RARE). Dupé, V., Davenne, M., Brocard, J., Dollé, P., Mark, M., Dierich, A., Chambon, P., Rijli, F.M. Development (1997) [Pubmed]
  14. Orientation of the Hoxa complex and placement of the Hd locus distal to Hoxa2 on mouse chromosome 6. Innis, J.W., Darling, S.M., Kazen-Gillespie, K., Post, L.C., Mortlock, D.P., Yang, T. Mamm. Genome (1996) [Pubmed]
  15. Mouse F9 teratocarcinoma stem cells expressing the stably transfected homeobox gene Hox 1.6 exhibit an altered morphology. Goliger, J.A., Gudas, L.J. Gene Expr. (1992) [Pubmed]
  16. Cadherin-6 expression transiently delineates specific rhombomeres, other neural tube subdivisions, and neural crest subpopulations in mouse embryos. Inoue, T., Chisaka, O., Matsunami, H., Takeichi, M. Dev. Biol. (1997) [Pubmed]
  17. Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. Chisaka, O., Musci, T.S., Capecchi, M.R. Nature (1992) [Pubmed]
  18. Region-specific expression in early chick and mouse embryos of Ghox-lab and Hox 1.6, vertebrate homeobox-containing genes related to Drosophila labial. Sundin, O.H., Busse, H.G., Rogers, M.B., Gudas, L.J., Eichele, G. Development (1990) [Pubmed]
  19. Molecular cloning and analysis of a group of genes differentially expressed in cells which overexpress the Hoxa-1 homeobox gene. Shen, J., Wu, H., Gudas, L.J. Exp. Cell Res. (2000) [Pubmed]
  20. Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation. Mamo, A., Krosl, J., Kroon, E., Bijl, J., Thompson, A., Mayotte, N., Girard, S., Bisaillon, R., Beslu, N., Featherstone, M., Sauvageau, G. Blood (2006) [Pubmed]
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