DLX3 explained

Homeobox protein DLX-3 is a protein that in humans is encoded by the DLX3 gene.^{[1] [2]}

Function

Dlx3 is a crucial regulator of hair follicle differentiation and cycling. Dlx3 transcription is mediated through Wnt, and colocalization of Dlx3 with phospho-SMAD1/5/8 is involved in the regulation of transcription by BMP signaling.^[3] Dlx3 transcription is also induced by BMP-2 through transactivation with SMAD1 and SMAD4.^[4]

Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 17.

Clinical significance

Mutations in this gene have been associated with the autosomal dominant conditions trichodentoosseous syndrome (TDO) and amelogenesis imperfecta with taurodontism.

Further reading

• Morasso MI, Radoja N . Dlx Genes, p63, and Ectodermal Dysplasias . Birth Defects Res. C . 75 . 3 . 163–71 . 2005 . 16187309 . 10.1002/bdrc.20047 . 1317295 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Nakamura S . Genomic analysis of a new mammalian distal-less gene: Dlx7 . Genomics . 38 . 3 . 314–24 . 1997 . 8975708 . 10.1006/geno.1996.0634 . vanc. Stock DW . Wydner KL . 3 . Bollekens . Jacques A. . Takeshita . Kenichi . Nagai . Brian M. . Chiba . Shigeru . Kitamura . Toshio . Freeland . Thomas M. . free .
• Price JA . Identification of a mutation in DLX3 associated with tricho-dento-osseous (TDO) syndrome . Hum. Mol. Genet. . 7 . 3 . 563–9 . 1998 . 9467018 . 10.1093/hmg/7.3.563 . vanc. Bowden DW . Wright JT . 3 . Pettenati . MJ . Hart . TC . free.
• Roberson MS . A role for the homeobox protein Distal-less 3 in the activation of the glycoprotein hormone alpha subunit gene in choriocarcinoma cells . J. Biol. Chem. . 276 . 13 . 10016–24 . 2001 . 11113121 . 10.1074/jbc.M007481200 . vanc. Meermann S . Morasso MI . 3 . Mulvaney-Musa . JM . Zhang . T . free .
• Park GT, Denning MF, Morasso MI . Phosphorylation of murine homeodomain protein Dlx3 by protein kinase C . FEBS Lett. . 496 . 1 . 60–5 . 2001 . 11343707 . 10.1016/S0014-5793(01)02398-5 . 1283141 . 2001FEBSL.496...60P .
• Peng L, Payne AH . AP-2 gamma and the homeodomain protein distal-less 3 are required for placental-specific expression of the murine 3 beta-hydroxysteroid dehydrogenase VI gene, Hsd3b6 . J. Biol. Chem. . 277 . 10 . 7945–54 . 2002 . 11773066 . 10.1074/jbc.M106765200 . free .
• Sumiyama K . Genomic structure and functional control of the Dlx3-7 bigene cluster . Proc. Natl. Acad. Sci. U.S.A. . 99 . 2 . 780–5 . 2002 . 11792834 . 10.1073/pnas.012584999 . 117382 . vanc. Irvine SQ . Stock DW . 3 . Weiss . KM . Kawasaki . K . Shimizu . N . Shashikant . CS . Miller . W . Ruddle . FH . 2002PNAS...99..780S . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Imabayashi H . Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis . Exp. Cell Res. . 288 . 1 . 35–50 . 2003 . 12878157 . 10.1016/S0014-4827(03)00130-7 . vanc. Mori T . Gojo S . 3 . Kiyono . T . Sugiyama . T . Irie . R . Isogai . T . Hata . J . Toyama . Y .
• Holland MP, Bliss SP, Berghorn KA, Roberson MS . A role for CCAAT/enhancer-binding protein beta in the basal regulation of the distal-less 3 gene promoter in placental cells . Endocrinology . 145 . 3 . 1096–105 . 2004 . 14670999 . 10.1210/en.2003-0777 . free .
• Haldeman RJ . Increased bone density associated with DLX3 mutation in the tricho-dento-osseous syndrome . Bone . 35 . 4 . 988–97 . 2005 . 15454107 . 10.1016/j.bone.2004.06.003 . vanc. Cooper LF . Hart TC . 3 . Phillips . Ceib . Boyd . Courtney . Lester . Gayle E. . Wright . J.Timothy .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . vanc. Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Dong J . DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism . Am. J. Med. Genet. A . 133 . 2 . 138–41 . 2005 . 15666299 . 10.1002/ajmg.a.30521 . vanc. Amor D . Aldred MJ . 3 . Gu . Tingting . Escamilla . Michael . MacDougall . Mary . 8482065 .
• Islam M, Lurie AG, Reichenberger E . Clinical features of tricho-dento-osseous syndrome and presentation of three new cases: an addition to clinical heterogeneity . Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics . 100 . 6 . 736–42 . 2006 . 16301156 . 10.1016/j.tripleo.2005.04.017 .
• Otsuki T . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries . DNA Res. . 12 . 2 . 117–26 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . vanc. Ota T . Nishikawa T . 3 . Hayashi . K . Suzuki . Y . Yamamoto . J . Wakamatsu . A . Kimura . K . Sakamoto . K . free .
• Morsczeck C . Gene expression of runx2, Osterix, c-fos, DLX-3, DLX-5, and MSX-2 in dental follicle cells during osteogenic differentiation in vitro . Calcif. Tissue Int. . 78 . 2 . 98–102 . 2006 . 16467978 . 10.1007/s00223-005-0146-0 . 7621703 .
• Berghorn KA . Smad6 represses Dlx3 transcriptional activity through inhibition of DNA binding . J. Biol. Chem. . 281 . 29 . 20357–67 . 2006 . 16687405 . 10.1074/jbc.M603049200 . vanc. Clark-Campbell PA . Han L . 3 . McGrattan . M . Weiss . RS . Roberson . MS . free.

Notes and References

1. Scherer SW, Heng HH, Robinson GW, Mahon KA, Evans JP, Tsui LC . Assignment of the human homolog of mouse Dlx3 to chromosome 17q21.3-q22 by analysis of somatic cell hybrids and fluorescence in situ hybridization . Mamm Genome . 6 . 4 . 310–1 . Aug 1995 . 7613049 . 10.1007/BF00352432 . 3088522 .
2. Web site: Entrez Gene: DLX3 distal-less homeobox 3.
3. Hwang J, Mehrani T, Millar SE, Morasso MI . Dlx3 is a crucial regulator of hair follicle differentiation and cycling . Development . 135 . 18 . 3149–59 . September 2008 . 18684741 . 2707782 . 10.1242/dev.022202 .
4. Park GT, Morasso MI . Bone morphogenetic protein-2 (BMP-2) transactivates Dlx3 through Smad1 and Smad4: alternative mode for Dlx3 induction in mouse keratinocytes . Nucleic Acids Res. . 30 . 2 . 515–22 . January 2002 . 11788714 . 99823 . 10.1093/nar/30.2.515 .