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Gene Review

Hoxd1  -  homeobox D1

Mus musculus

Synonyms: Homeobox protein Hox-4.9, Homeobox protein Hox-D1, Hox-4.9, Hoxd-1
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High impact information on Hoxd1

  • Here, we show that Hoxd1 and other Hox genes display dynamic stripes of expression within presomitic mesoderm [1].
  • This mechanism appears to depend upon Notch signaling, as mice deficient for RBPJk, the effector of the Notch pathway, showed severely reduced Hoxd gene expression in presomitic mesoderm [1].
  • Among them are the loss of Hoxd10 function, the sum of remaining Hoxd gene activity, and the ectopic gain of function of the neighboring gene Evx2, all contributing to the mispositioning, the absence, or misidentification of specific lumbo-sacral pools of motoneurons, nerve root homeosis, and hindlimb innervation defects [2].
  • Hox-1.11 and Hox-4.9 homeobox genes [3].
  • Results support genome duplication before divergence of zebrafish and pufferfish lineages, followed by loss of a Hoxc cluster in the pufferfish lineage and loss of a Hoxd cluster in the zebrafish lineage [4].

Biological context of Hoxd1

  • Mouse Hox-1.11 and Hox-4.9 genes were cloned, and the nucleotide sequences of the homeobox regions were determined [3].
  • Interspecies exchange of a Hoxd enhancer in vivo induces premature transcription and anterior shift of the sacrum [5].
  • A 0.4-cM interval containing the Ulnaless locus has been defined on mouse chromosome 2, which has identified Ulnaless as a possible allele of a Hoxd cluster gene(s) [6].

Anatomical context of Hoxd1

  • 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 [7].
  • By late neurogenesis and through mid-gestation (E9.0-E11.5), Hox-4.9 is no longer detected in lateral mesoderm but is found instead in a restricted region of presumed trunk neural crest and in the dermatome [8].
  • Several 5' members of the Hoxd cluster are expressed in nested posterior-distal domains of the limb bud suggesting a role in regulating anteroposterior pattern of skeletal elements [9].
  • Here we describe mice that are lacking all Hoxa and Hoxd functions in their forelimbs [10].

Other interactions of Hoxd1

  • While relief from a cluster-encompassing repression was shown to lead to all Hoxd genes being expressed like the 3'most of them, Hoxd1 (Kondo and Duboule, 1999), the molecular basis of initial activation of this 3'most gene, is not understood yet [11].
  • Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the developing diencephalon [7].

Analytical, diagnostic and therapeutic context of Hoxd1


  1. Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock. Zákány, J., Kmita, M., Alarcon, P., de la Pompa, J.L., Duboule, D. Cell (2001) [Pubmed]
  2. HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside. Tarchini, B., Huynh, T.H., Cox, G.A., Duboule, D. Genes Dev. (2005) [Pubmed]
  3. Hox-1.11 and Hox-4.9 homeobox genes. Nazarali, A., Kim, Y., Nirenberg, M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  4. Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin fish. Amores, A., Suzuki, T., Yan, Y.L., Pomeroy, J., Singer, A., Amemiya, C., Postlethwait, J.H. Genome Res. (2004) [Pubmed]
  5. Interspecies exchange of a Hoxd enhancer in vivo induces premature transcription and anterior shift of the sacrum. Gérard, M., Zákány, J., Duboule, D. Dev. Biol. (1997) [Pubmed]
  6. Genetic and physical mapping of the mouse Ulnaless locus. Peichel, C.L., Abbott, C.M., Vogt, T.F. Genetics (1996) [Pubmed]
  7. 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]
  8. Isolation and analysis of embryonic expression of Hox-4.9, a member of the murine labial-like gene family. Frohman, M.A., Martin, G.R. Mech. Dev. (1992) [Pubmed]
  9. 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]
  10. Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function. Kmita, M., Tarchini, B., Zàkàny, J., Logan, M., Tabin, C.J., Duboule, D. Nature (2005) [Pubmed]
  11. 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]
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