Alternative titles; symbols
HGNC Approved Gene Symbol: HOXD9
Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38): 2:176,122,719-176,124,937 (from NCBI)
The anterior to posterior (A-P) polarity of the tetrapod limb is determined by the confined expression of Sonic hedgehog (SHH; 600725) at the posterior margin of developing early limb buds, under the control of HOX proteins encoded by gene members of both the HoxA and HoxD clusters. Tarchini et al. (2006) used a set of partial deletions to show that only the last 4 Hox paralogy groups can elicit this response: i.e., precisely those genes whose expression is excluded from most anterior limb bud cells owing to their collinear transcriptional activation. Deletion of Hoxd10 (142984), Hoxd11 (142986), Hoxd12 (142988), and Hoxd13 (142989) led to Hoxd9 upregulation in posterior cells; however, even a robust dose of Hoxd9 was unable to trigger Shh expression, demonstrating that HOXD10-HOXD13 expression is essential to elicit Shh expression.
As reviewed by Acampora et al. (1989), the homeobox region 4 includes at least 6 homeobox genes in 70 kb of DNA located on chromosome 2q31. The order of the genes, from 5-prime to 3-prime, is HOX4F (HOXD11; 142986), HOX4D (HOXD10; 142984), HOX4C (HOXD9), HOX4E (HOXD8; 142985), HOX4B (HOXD4; 142981), HOX4A (HOXD3; 142980). Genes HOX4B (HOXD4) through HOX4G (HOXD1; 142987) are homologous to mouse genes Hox-4.2 through Hox-4.7, respectively. Hox-4.2 through Hox-4.7 were previously thought to be Hox-5 genes. See 142988 and 142989, respectively, for 2 additional contiguous genes, HOX4H (HOXD12) and HOX4I (HOXD13).
Acampora, D., D'Esposito, M., Faiella, A., Pannese, M., Migliaccio, E., Morelli, F., Stornaiuolo, A., Nigro, V., Simeone, A., Boncinelli, E. The human HOX gene family. Nucleic Acids Res. 17: 10385-10402, 1989. [PubMed: 2574852] [Full Text: https://doi.org/10.1093/nar/17.24.10385]
Tarchini, B., Duboule, D., Kmita, M. Regulatory constraints in the evolution of the tetrapod limb anterior-posterior polarity. Nature 443: 985-988, 2006. [PubMed: 17066034] [Full Text: https://doi.org/10.1038/nature05247]