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Gene Review

Hoxa2  -  homeobox A2

Mus musculus

Synonyms: AI324701, HOX1.11, Homeobox protein Hox-1.11, Homeobox protein Hox-A2, Hox-1.11, ...
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Disease relevance of Hoxa2

  • Interestingly, the abnormal trajectory of two of these muscles, the styloglossus and the stylohyoideus, blocked the attachment of the hyoglossus to the greater horn of the hyoid, which in turn correlated exactly with the presence of cleft palate in Hoxa2 mutants [1].
  • Using transgenic analysis with E. coli lacZ reporter genes we have identified and mapped an r3/r5 enhancer in the 5' flanking region of the Hoxa-2 gene [2].

High impact information on Hoxa2


Chemical compound and disease context of Hoxa2


Biological context of Hoxa2

  • Temporal requirement of Hoxa2 in cranial neural crest skeletal morphogenesis [8].
  • Immunocytochemical analysis of primary mixed glial cultures demonstrated that Hoxa2 was expressed throughout oligodendrogenesis, diminishing only with the acquisition of a myelinating phenotype [9].
  • One such TF is the homeobox gene Hoxa2, which was recently shown to be expressed by O4(+) pro-oligodendrocytes [9].
  • We mapped lit (by phenotype) relative to Hoxa2 and Igk on 72 F2 chromosomes of offspring of a B6CZ lit/ + x B6FVB lit/ + intercross and 18 chromosomes of offspring of a B6FVB lit/ + intercross [10].
  • Unexpectedly, in Hoxa1/Hoxa2 double mutants, the penetrance of cleft palate is dramatically reduced [1].

Anatomical context of Hoxa2

  • Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse [11].
  • Here, we show that Hoxa2 is selectively required in cranial neural crest cells (NCCs) [8].
  • In Hoxa2 mouse mutants, the hyoid skeleton is replaced by a duplicated set of mandibular and middle ear structures [8].
  • Hence, although Hoxa2 is expressed throughout OG development, it does not appear to be critical for early stages of oligodendrogenesis in the murine spinal cord [9].
  • Hoxd1 expression decreased significantly in the third stage of diencephalic development (E16-postnatal) such that only Hoxa2 expression persisted in the diencephalon of newborn mice [12].

Associations of Hoxa2 with chemical compounds

  • We have produced complete and reversible inactivation of the Hoxa2 gene in the mouse using the control elements of the tetracycline-resistance operon [13].
  • Experimental loss of the tympanic ring by retinoic acid treatment, or duplication of the ring in Hoxa-2 null mutant embryos, resulted in corresponding alterations in formation of the external acoustic meatus [14].
  • The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos [15].

Regulatory relationships of Hoxa2


Other interactions of Hoxa2

  • 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 [18].
  • Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the developing diencephalon [12].
  • Moreover, Hoxa2 and Hoxb2 can functionally synergize in controlling the development of ventral neuronal subtypes in rhombomere 3 (r3) [6].
  • To investigate this problem, we have cloned and sequenced the intergenic region between Hoxa2 and Hoxa3 in the chick HoxA complex and used it for making comparative analyses with the respective human, mouse, and horn shark regions [19].
  • There was a clear loss of expression in r3, which indicated that Hoxa-2 was downstream of Krox-20 [2].
  • We propose that Six2 acts to mediate Hoxa2 control over the insulin-like growth factor pathway during branchial arch development [20].

Analytical, diagnostic and therapeutic context of Hoxa2


  1. Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants. Barrow, J.R., Capecchi, M.R. Development (1999) [Pubmed]
  2. Segmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox-20. Nonchev, S., Vesque, C., Maconochie, M., Seitanidou, T., Ariza-McNaughton, L., Frain, M., Marshall, H., Sham, M.H., Krumlauf, R., Charnay, P. Development (1996) [Pubmed]
  3. SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Dobreva, G., Chahrour, M., Dautzenberg, M., Chirivella, L., Kanzler, B., Fariñas, I., Karsenty, G., Grosschedl, R. Cell (2006) [Pubmed]
  4. Hoxa-2 mutant mice exhibit homeotic transformation of skeletal elements derived from cranial neural crest. Gendron-Maguire, M., Mallo, M., Zhang, M., Gridley, T. Cell (1993) [Pubmed]
  5. A homeotic transformation is generated in the rostral branchial region of the head by disruption of Hoxa-2, which acts as a selector gene. Rijli, F.M., Mark, M., Lakkaraju, S., Dierich, A., Dollé, P., Chambon, P. Cell (1993) [Pubmed]
  6. Hoxa2 and Hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain. Davenne, M., Maconochie, M.K., Neun, R., Pattyn, A., Chambon, P., Krumlauf, R., Rijli, F.M. Neuron (1999) [Pubmed]
  7. Temporal and spatial expression of Hoxa-2 during murine palatogenesis. Nazarali, A., Puthucode, R., Leung, V., Wolf, L., Hao, Z., Yeung, J. Cell. Mol. Neurobiol. (2000) [Pubmed]
  8. Temporal requirement of Hoxa2 in cranial neural crest skeletal morphogenesis. Santagati, F., Minoux, M., Ren, S.Y., Rijli, F.M. Development (2005) [Pubmed]
  9. Early stages of oligodendrocyte development in the embryonic murine spinal cord proceed normally in the absence of Hoxa2. Nicolay, D.J., Doucette, J.R., Nazarali, A.J. Glia (2004) [Pubmed]
  10. The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse chromosome 6. Chua, S.C., Hennessey, K., Zeitler, P., Leibel, R.L. Mamm. Genome (1993) [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. Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the developing diencephalon. Wolf, L.V., Yeung, J.M., Doucette, J.R., Nazarali, A.J. Neuroreport (2001) [Pubmed]
  13. Reversible gene inactivation in the mouse. Mallo, M., Kanzler, B., Ohnemus, S. Genomics (2003) [Pubmed]
  14. Development of the mammalian ear: coordinate regulation of formation of the tympanic ring and the external acoustic meatus. Mallo, M., Gridley, T. Development (1996) [Pubmed]
  15. The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos. Taneja, R., Thisse, B., Rijli, F.M., Thisse, C., Bouillet, P., Dollé, P., Chambon, P. Dev. Biol. (1996) [Pubmed]
  16. Mesenchymal patterning by Hoxa2 requires blocking Fgf-dependent activation of Ptx1. Bobola, N., Carapuço, M., Ohnemus, S., Kanzler, B., Leibbrandt, A., Neubüser, A., Drouin, J., Mallo, M. Development (2003) [Pubmed]
  17. Hoxa2 downregulates Six2 in the neural crest-derived mesenchyme. Kutejova, E., Engist, B., Mallo, M., Kanzler, B., Bobola, N. Development (2005) [Pubmed]
  18. 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]
  19. Conservation and diversity in the cis-regulatory networks that integrate information controlling expression of Hoxa2 in hindbrain and cranial neural crest cells in vertebrates. Tümpel, S., Maconochie, M., Wiedemann, L.M., Krumlauf, R. Dev. Biol. (2002) [Pubmed]
  20. Six2 functions redundantly immediately downstream of Hoxa2. Kutejova, E., Engist, B., Self, M., Oliver, G., Kirilenko, P., Bobola, N. Development (2008) [Pubmed]
  21. Murine Hox-1.11 homeobox gene structure and expression. Tan, D.P., Ferrante, J., Nazarali, A., Shao, X., Kozak, C.A., Guo, V., Nirenberg, M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
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