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Gene Review

Hoxd12  -  homeobox D12

Mus musculus

Synonyms: Homeobox protein Hox-4.7, Homeobox protein Hox-5.6, Homeobox protein Hox-D12, Hox-4.7, Hox-5.6, ...
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Disease relevance of Hoxd12

  • Using a gain-of-function approach, we find that Hoxd-12 misexpression in transgenic mice produces apparent transformations of anterior digits to posterior morphology and digit duplications, while associated tibial hemimelia and other changes indicate that formation/growth of certain skeletal elements is selectively inhibited [1].
  • Homeobox-containing genes in teratocarcinoma embryoid bodies: a possible role for Hox-D12 (Hox-4.7) in establishing the extraembryonic endoderm lineage in the mouse [2].

High impact information on Hoxd12

  • To investigate the mechanistic basis of this phenomenon, we used the ES cell technology and the loxP/Cre system to engineer a conditional fusion of the 5' exon of Hoxd-13 with the 3' exon of Hoxd-12 [3].
  • The cloning, characterization and developmental expression patterns of two novel murine Hox genes, Hox-4.6 and Hox-4.7, are reported [4].
  • Analyses of animals homozygous for the HoxDRXI mutant allele revealed the function of this region in controlling Hoxd-12 expression in the presumptive posterior zeugopod where it genetically interacts with Hoxa-11 [5].
  • The regulatory potential of this region XI (RXI) was first assayed in the context of a Hoxd-12/lacZ reporter transgene and shown to direct reporter gene expression in posterior limb buds [5].
  • Downregulation of Hoxd-12 expression was also detected in the trunk suggesting that RXI may mediate a rather general function in the activation of Hoxd-12 [5].

Anatomical context of Hoxd12

  • Three of these genes, Hoxd11, Hoxd12, and Hoxd13, act synergistically to pattern the hindlimb autopod [6].
  • By using an inversion of and a large deficiency in the mouse HoxD cluster, we found that a perturbation in the early collinear expression of Hoxd11, Hoxd12, and Hoxd13 in limb buds led to a loss of asymmetry [7].
  • Misexpression of Hoxd-12 in other lateral plate derivatives (sternum, pelvis) likewise phenocopies several luxoid/luxate class mouse mutants that all share ectopic Shh signalling [1].
  • In addition, ld limbs show a severe decrease in the expression of several mesodermal markers, including sonic hedgehog (shh), a marker for the polarizing region and Hoxd-12, a marker for posterior mesoderm [8].
  • In situ hybridizations demonstrated that prior to induction of supernumerary digits, the tooth germ grafts induced expression in host tissue of Hoxd-12 and Hoxd-13 [9].

Physical interactions of Hoxd12


Regulatory relationships of Hoxd12

  • Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop [1].

Other interactions of Hoxd12

  • The observations that Hoxd-12 and Hoxd-13 expression patterns were extended anteriorly provide a molecular basis for the posterior transformation of the anterior digit [10].
  • This suggests that feedback activation of Shh expression may be a major function of Hoxd-12 [1].
  • Accordingly, we show that mutant embryos ectopically express the pattern-determining genes fibroblast growth factor 4 (fgf-4), sonic hedgehog (shh), and Hoxd-12 in the anterior region of the limb [11].


  1. Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop. Knezevic, V., De Santo, R., Schughart, K., Huffstadt, U., Chiang, C., Mahon, K.A., Mackem, S. Development (1997) [Pubmed]
  2. Homeobox-containing genes in teratocarcinoma embryoid bodies: a possible role for Hox-D12 (Hox-4.7) in establishing the extraembryonic endoderm lineage in the mouse. Labosky, P.A., Weir, M.P., Grabel, L.B. Dev. Biol. (1993) [Pubmed]
  3. Control of colinearity in AbdB genes of the mouse HoxD complex. Kondo, T., Zákány, J., Duboule, D. Mol. Cell (1998) [Pubmed]
  4. Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. Izpisúa-Belmonte, J.C., Falkenstein, H., Dollé, P., Renucci, A., Duboule, D. EMBO J. (1991) [Pubmed]
  5. Genetic analysis of a Hoxd-12 regulatory element reveals global versus local modes of controls in the HoxD complex. Hérault, Y., Beckers, J., Kondo, T., Fraudeau, N., Duboule, D. Development (1998) [Pubmed]
  6. Targeted disruption of Hoxd9 and Hoxd10 alters locomotor behavior, vertebral identity, and peripheral nervous system development. de la Cruz, C.C., Der-Avakian, A., Spyropoulos, D.D., Tieu, D.D., Carpenter, E.M. Dev. Biol. (1999) [Pubmed]
  7. A dual role for Hox genes in limb anterior-posterior asymmetry. Zákány, J., Kmita, M., Duboule, D. Science (2004) [Pubmed]
  8. Formin isoforms are differentially expressed in the mouse embryo and are required for normal expression of fgf-4 and shh in the limb bud. Chan, D.C., Wynshaw-Boris, A., Leder, P. Development (1995) [Pubmed]
  9. Polarizing activity, Sonic hedgehog, and tooth development in embryonic and postnatal mouse. Koyama, E., Yamaai, T., Iseki, S., Ohuchi, H., Nohno, T., Yoshioka, H., Hayashi, Y., Leatherman, J.L., Golden, E.B., Noji, S., Pacifici, M. Dev. Dyn. (1996) [Pubmed]
  10. Targeted misexpression of constitutively active BMP receptor-IB causes bifurcation, duplication, and posterior transformation of digit in mouse limb. Zhang, Z., Yu, X., Zhang, Y., Geronimo, B., Lovlie, A., Fromm, S.H., Chen, Y. Dev. Biol. (2000) [Pubmed]
  11. Polydactylous limbs in Strong's Luxoid mice result from ectopic polarizing activity. Chan, D.C., Laufer, E., Tabin, C., Leder, P. Development (1995) [Pubmed]
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