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

• Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome [4].

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

• In order to study the role of DLX genes during embryonic development in human, DLX5 expression pattern was investigated in 6- to 11-week-old human embryos [10].
• Furthermore, during the bud and cap stages of tooth morphogenesis, the asymmetric expression of DLX5 in the dental epithelium and dental mesenchyme may contribute to the complex patterning of human tooth shape [10].
• During odontogenesis from bud to late cap stages, DLX5 transcripts were present in both dental epithelium and mesenchyme tissues [10].
• A DLX5 PCR fragment was amplified from a human dental cDNA library subcloned and used for in situ hybridization investigations [10].
• Dlx5- and Dlx6-mediated chondrogenesis: Differential domain requirements for a conserved function [1].

Anatomical context of DLX5

• Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5 [11].
• To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization [11].
• The observed expression pattern of DLX5 homeogene extends the proposed site-specific combination of homeogene expression in neural crest derived cells to human specific dentition [10].
• DLX5 gene expression became restricted to progenitor cells of developing tooth germs, bones and cartilages of mandible and maxilla [10].
• DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation [12].

Associations of DLX5 with chemical compounds

• Cycloheximide pretreatment indicated that Dex signaling immediately increases expressions of the C/EBPs and Dlx5, while expressions of the rest of the genes require de novo protein synthesis [13].
• Brain-derived neurotrophic factor enhances glutamate neurotransmission at excitatory synapses, whereas Dlx5 is expressed in most GABAergic neurons and stimulates the synthesis of GABA [14].

Physical interactions of DLX5

• Recent reports indicate that MeCP2 controls the expression of brain-derived neurotrophic factor and the DNA-binding homeobox protein Dlx5 [14].

Regulatory relationships of DLX5

• Msx2 and Dlx5 are homeodomain proteins that play an important role in osteoblast differentiation and whose expression is induced by bone morphogenetic proteins [15].

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

• Dlx5 responsiveness to these elements was confirmed by gel mobility shift assay and site-directed mutagenesis [9].

References