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Gene Review

DLX5  -  distal-less homeobox 5

Homo sapiens

Synonyms: Homeobox protein DLX-5
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Disease relevance of DLX5

  • Dlx5 and Dlx6 are functionally redundant regulators of chondrocyte hypertrophy [1].
  • Dlx5 gene mutation leads to cranial dismorphogenesis which differs from the previously studied craniosynostosis syndromes [Development 126 (1999), 3795; Development 126 (1999), 3831] [2].
  • Treatment of lung cancer cells with small interfering RNAs for DLX5 effectively knocked down its expression and suppressed cell growth [3].

Psychiatry related information on DLX5


High impact information on DLX5

  • The two human genes, DLX5 and DLX6, are closely linked in an inverted convergent configuration in a region of chromosome 7, at 7q22 [5].
  • Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome [6].
  • Later, some DLX5-expressing cells become internalized into the ventral forebrain and the neural crest at the hindbrain level [7].
  • Taken together, our data show that RUNX2 is a direct regulator of Bsp in osteoblasts and that it functions in cooperation with DLX5 or a related factor to activate osteoblast-specific gene expression [8].
  • Our previous results indicate that Dlx5 mediates BMP-2-induced Runx2 expression and osteoblast differentiation (Lee, M.-H., Kim, Y-J., Kim, H-J., Park, H-D., Kang, A-R., Kyung, H.-M., Sung, J-H., Wozney, J. M., Kim, H-J., and Ryoo, H-M. (2003) J. Biol. Chem. 278, 34387-34394) [9].

Biological context of DLX5


Anatomical context of DLX5


Associations of DLX5 with chemical compounds


Physical interactions of DLX5


Regulatory relationships of DLX5


Other interactions of DLX5

  • Finally, co-immunoprecipitation assays detected a physical complex containing DLX5 and RUNX2 [8].
  • BACKGROUND: Linkage studies in autism have identified susceptibility loci on chromosomes 2q and 7q, regions containing the DLX1/2 and DLX5/6 bigene clusters [16].
  • In addition, MEF stimulated the transcription of a negative mediator Msx2, and a transcriptional repressor, Mab21L1, and suppressed the transcription of a positive mediator, Dlx5 in osteoblast differentiation [17].
  • We screened 10 consecutive ultraconserved elements in, or flanking, the genes DLX5/6, AUTS2 and FOXP2 on chromosome 7q [18].
  • Comparison of these fate maps with gene expression patterns at equivalent stages reveals molecular heterogeneity of otic precursor cells in terms of their expression of dlx5, msx1, Six4, and ERNI [19].

Analytical, diagnostic and therapeutic context of DLX5


  1. Dlx5- and Dlx6-mediated chondrogenesis: Differential domain requirements for a conserved function. Hsu, S.H., Noamani, B., Abernethy, D.E., Zhu, H., Levi, G., Bendall, A.J. Mech. Dev. (2006) [Pubmed]
  2. BMP signals regulate Dlx5 during early avian skull development. Holleville, N., Quilhac, A., Bontoux, M., Monsoro-Burq, A.H. Dev. Biol. (2003) [Pubmed]
  3. Activation of placenta-specific transcription factor distal-less homeobox 5 predicts clinical outcome in primary lung cancer patients. Kato, T., Sato, N., Takano, A., Miyamoto, M., Nishimura, H., Tsuchiya, E., Kondo, S., Nakamura, Y., Daigo, Y. Clin. Cancer Res. (2008) [Pubmed]
  4. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Horike, S., Cai, S., Miyano, M., Cheng, J.F., Kohwi-Shigematsu, T. Nat. Genet. (2005) [Pubmed]
  5. Cloning and characterization of two members of the vertebrate Dlx gene family. Simeone, A., Acampora, D., Pannese, M., D'Esposito, M., Stornaiuolo, A., Gulisano, M., Mallamaci, A., Kastury, K., Druck, T., Huebner, K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome. Bapat, S., Galande, S. Bioessays (2005) [Pubmed]
  7. Ectodermal patterning in the avian embryo: epidermis versus neural plate. Pera, E., Stein, S., Kessel, M. Development (1999) [Pubmed]
  8. Cooperative interactions between RUNX2 and homeodomain protein-binding sites are critical for the osteoblast-specific expression of the bone sialoprotein gene. Roca, H., Phimphilai, M., Gopalakrishnan, R., Xiao, G., Franceschi, R.T. J. Biol. Chem. (2005) [Pubmed]
  9. Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter. Lee, M.H., Kim, Y.J., Yoon, W.J., Kim, J.I., Kim, B.G., Hwang, Y.S., Wozney, J.M., Chi, X.Z., Bae, S.C., Choi, K.Y., Cho, J.Y., Choi, J.Y., Ryoo, H.M. J. Biol. Chem. (2005) [Pubmed]
  10. Expression of DLX5 during human embryonic craniofacial development. Davideau, J.L., Demri, P., Gu, T.T., Simmons, D., Nessman, C., Forest, N., MacDougall, M., Berdal, A. Mech. Dev. (1999) [Pubmed]
  11. Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development. Davideau, J.L., Demri, P., Hotton, D., Gu, T.T., MacDougall, M., Sharpe, P., Forest, N., Berdal, A. Pediatr. Res. (1999) [Pubmed]
  12. DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. Eisenstat, D.D., Liu, J.K., Mione, M., Zhong, W., Yu, G., Anderson, S.A., Ghattas, I., Puelles, L., Rubenstein, J.L. J. Comp. Neurol. (1999) [Pubmed]
  13. Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line, ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast differentiation. Ito, S., Suzuki, N., Kato, S., Takahashi, T., Takagi, M. Bone (2007) [Pubmed]
  14. Rett syndrome and neuronal development. Johnston, M.V., Blue, M.E., Naidu, S. J. Child Neurol. (2005) [Pubmed]
  15. A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1. Sasaki, A., Masuda, Y., Iwai, K., Ikeda, K., Watanabe, K. J. Biol. Chem. (2002) [Pubmed]
  16. Analysis of four DLX homeobox genes in autistic probands. Hamilton, S.P., Woo, J.M., Carlson, E.J., Ghanem, N., Ekker, M., Rubenstein, J.L. BMC Genet. (2005) [Pubmed]
  17. The suppressive effect of myeloid elf-1-like factor (MEF) in osteogenic differentiation. Kim, Y.J., Kim, B.G., Lee, S.J., Lee, H.K., Lee, S.H., Ryoo, H.M., Cho, J.Y. J. Cell. Physiol. (2007) [Pubmed]
  18. Autism and ultraconserved non-coding sequence on chromosome 7q. Richler, E., Reichert, J.G., Buxbaum, J.D., McInnes, L.A. Psychiatr. Genet. (2006) [Pubmed]
  19. Extensive cell movements accompany formation of the otic placode. Streit, A. Dev. Biol. (2002) [Pubmed]
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