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Nkx3-2  -  NK3 homeobox 2

Mus musculus

Synonyms: Bagpipe homeobox protein homolog 1, Bapx1, Homeobox protein NK-3 homolog B, Homeobox protein Nkx-3.2, NKX3.2, ...
 
 
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Disease relevance of Bapx1

 

High impact information on Bapx1

  • Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1-/- mice [2].
  • The homeobox genes Hox11 and Bapx1, shown previously to be essential regulators of spleen organogenesis, and a lacZ reporter introduced into the capsulin locus, were expressed in the early splenic primordium, derived from the splanchnic mesoderm, of homozygous mutant embryos [3].
  • Bapx1, similar to Drosophila, does have a conspicuous role in gut mesoderm; however, this appears to be restricted to development of the spleen [4].
  • We postulate that Bapx1 confers the capacity of cells to interact with the notochord, effecting inductive interactions essential for development of the vertebral column and chondrocranium [4].
  • 2. Furthermore, the recruitment of an HDAC/Sin3A complex to Nkx3.2 requires that Nkx3.2 interact with Smad1 and -4 [5].
 

Biological context of Bapx1

  • During embryogenesis, Bapx1 is expressed in a discrete domain within the mandibular component of the first branchial arch and later in the primordia of middle ear-associated bones, the gonium and tympanic ring [6].
  • The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen [7].
  • Our previous studies in both mouse and human identified the Bapx1 homeobox gene, a member of the NK gene family, as one of the earliest markers for prechondrogenic cells that will subsequently undergo mesenchymal condensation, cartilage production and, finally, endochondral bone formation [7].
  • Loss of Bapx1 is accompanied by an increase in apoptotic cell death in affected tissues, although cell cycling rates are unaltered [7].
  • The enhanced skeletal phenotype of double null mutants compared to the single Bapx1 mutation demonstrates that Nkx3.1 contributes to the formation of the axial skeleton in addition to the Bapx1 gene [8].
 

Anatomical context of Bapx1

  • Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation [1].
  • Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution [6].
  • In addition, Bapx1 is expressed both within and surrounding the incus and the malleus [6].
  • Contrary to expectations, murine Bapx1 does not affect the articulation of the malleus and incus [6].
  • Bapx1 null mice are affected by a perinatal lethal skeletal dysplasia and asplenia, with severe malformation or absence of specific bones of the vertebral column and cranial bones of mesodermal origin, with the most severely affected skeletal elements corresponding to ventral structures associated with the notochord [7].
 

Associations of Bapx1 with chemical compounds

 

Regulatory relationships of Bapx1

  • Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome [10].
  • We show that this change in role of Bapx1 following the transition to the mammalian ossicle configuration is not due to a change in expression pattern but results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be essential in joint formation [6].
 

Other interactions of Bapx1

  • Additionally, we demonstrate that while Nkx3.2 and Pod1 control spleen development via separate pathways, Pbx1 genetically regulates key players in both pathways, and thus emerges as a central hierarchical co-regulator in spleen genesis [11].
  • We show that, in combination with goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine middle ear [6].
  • Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in sclerotomal development of the mouse [8].
  • Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated Shh signaling in the developing limb [12].
  • We show that transgenic mice overexpressing Bapx1 are affected by skeletal defects including hindlimb preaxial polydactyly and tibial hypoplasia [12].
 

Analytical, diagnostic and therapeutic context of Bapx1

References

  1. Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation. Provot, S., Kempf, H., Murtaugh, L.C., Chung, U.I., Kim, D.W., Chyung, J., Kronenberg, H.M., Lassar, A.B. Development (2006) [Pubmed]
  2. Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1-/- mice. Asayesh, A., Sharpe, J., Watson, R.P., Hecksher-Sørensen, J., Hastie, N.D., Hill, R.E., Ahlgren, U. Genes Dev. (2006) [Pubmed]
  3. The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis. Lu, J., Chang, P., Richardson, J.A., Gan, L., Weiler, H., Olson, E.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. The mouse bagpipe gene controls development of axial skeleton, skull, and spleen. Lettice, L.A., Purdie, L.A., Carlson, G.J., Kilanowski, F., Dorin, J., Hill, R.E. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Kim, D.W., Lassar, A.B. Mol. Cell. Biol. (2003) [Pubmed]
  6. Bapx1 regulates patterning in the middle ear: altered regulatory role in the transition from the proximal jaw during vertebrate evolution. Tucker, A.S., Watson, R.P., Lettice, L.A., Yamada, G., Hill, R.E. Development (2004) [Pubmed]
  7. The murine Bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. Tribioli, C., Lufkin, T. Development (1999) [Pubmed]
  8. Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in sclerotomal development of the mouse. Herbrand, H., Pabst, O., Hill, R., Arnold, H.H. Mech. Dev. (2002) [Pubmed]
  9. Characterization of Nkx3.2 DNA binding specificity and its requirement for somitic chondrogenesis. Kim, D.W., Kempf, H., Chen, R.E., Lassar, A.B. J. Biol. Chem. (2003) [Pubmed]
  10. Pax1 and Pax9 activate Bapx1 to induce chondrogenic differentiation in the sclerotome. Rodrigo, I., Hill, R.E., Balling, R., Münsterberg, A., Imai, K. Development (2003) [Pubmed]
  11. A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Brendolan, A., Ferretti, E., Salsi, V., Moses, K., Quaggin, S., Blasi, F., Cleary, M.L., Selleri, L. Development (2005) [Pubmed]
  12. Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated Shh signaling in the developing limb. Tribioli, C., Lufkin, T. Dev. Dyn. (2006) [Pubmed]
  13. Targeted disruption of the homeobox transcription factor Bapx1 results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation. Akazawa, H., Komuro, I., Sugitani, Y., Yazaki, Y., Nagai, R., Noda, T. Genes Cells (2000) [Pubmed]
 
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