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Gene Review

Dlx1  -  distal-less homeobox 1

Mus musculus

Synonyms: DII B, Dlx, Dlx-1, Homeobox protein DLX-1
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Disease relevance of Dlx1


High impact information on Dlx1


Biological context of Dlx1

  • To determine if the overlaps are a result of the conservation of enhancer sequences between paralogous clusters, we compared the Dlx1/2 and the Dlx5/Dlx6 intergenic regions from human, mouse, zebrafish, and from two pufferfish, Spheroides nephelus and Takifugu rubripes [7].
  • Although Dlx1 knockout mice did not display any obvious developmental defects in thymus or thymocyte development, the expression of these homeobox genes in neural crest derivatives suggests a possible role in cell migration and development that may overlap with other homeobox genes [8].
  • Dlx homeobox genes of vertebrates are generally arranged as three bigene clusters on distinct chromosomes [7].
  • Little is known of the regulatory architecture that is responsible for Dlx gene expression in developing arches [9].
  • LacZ transgene expression containing I12a is restricted to a subset of Dlx-expressing ectomesenchyme in the first arch [9].

Anatomical context of Dlx1

  • We have identified two distinct cis-acting regulatory sequences, I12a and I56i, in the intergenic regions of the Dlx1/2 and Dlx5/6 clusters that act as enhancers in the arch mesenchyme [9].
  • Our results support a possible role for Dlx1 and Dlx2 in inner retinal development and in the terminal differentiation and/or maintenance of INL interneurons and ganglion cells in the adult [10].
  • Identification and characterization of a novel transcript down-regulated in Dlx1/Dlx2 and up-regulated in Pax6 mutant telencephalon [11].
  • The expression of Dlx1 and Arx in the presumptive ventral thalamus extended as far as ZLI and overlapped with that of Brx1 [12].
  • Significantly, Dlx1 is expressed in the third branchial arch, which contributes to the thymus [8].

Associations of Dlx1 with chemical compounds

  • Despite late appearance of gamma-aminobutyric acid (GABA)ergic cells in the dorsal lateral geniculate nucleus of mice, no Dlx genes, which promote formation of a GABAergic phenotype elsewhere, were detected in dorsal thalamus [13].
  • These findings suggest that Dlx-1 and -2 do not play a direct role in DA phenotypic differentiation and TH gene regulation in adult OB [14].

Regulatory relationships of Dlx1

  • Dlx1 is a member of the distal-less homeobox gene family that has been shown to regulate embryonic craniofacial development [8].
  • Dlx-5 appears to be co-expressed with Dlx-1 and -2 in the SVZ, but is also expressed in the postmitotic cells of the mantle [15].
  • Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression [16].
  • Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures of Dlx1/2 mutants [17].
  • Therefore, our results suggest evolutionarily conserved functions of Dlx genes in regulating Arx expression between Drosophila and vertebrates [18].
  • We demonstrate that Dlx1&2 negatively regulate Olig2-dependant OPC formation and that Mash1 promotes OPC formation by restricting the number of Dlx+ progenitors [19].

Other interactions of Dlx1

  • Dlx-1 and Dlx-2 are expressed in two separate regions of the forebrain in an identical pattern [20].
  • The Gbx-2 gene is expressed in four domains, two of which share sharp boundaries with the domains of the Dlx genes [20].
  • Dlx1/2 double homozygous mutants formed ventral thalamic neurons, but these neurons lacked PAX6, ISL1, and TH expression [21].
  • The correlation of DLX2 with GABA expression in the mouse retina closely mirrors the relationship of DLX2 to GABAergic neuronal differentiation in the embryonic forebrain, including neocortex, olfactory bulb and hippocampus, signifying a conservation of function of Dlx genes in the developing central nervous system [10].
  • Transcripts for multiple Dlx family members and Lhx2 were repeatedly detected in this screen [8].

Analytical, diagnostic and therapeutic context of Dlx1


  1. Dlx gene expression during chick inner ear development. Brown, S.T., Wang, J., Groves, A.K. J. Comp. Neurol. (2005) [Pubmed]
  2. DLX genes as targets of ALL-1: DLX 2,3,4 down-regulation in t(4;11) acute lymphoblastic leukemias. Ferrari, N., Palmisano, G.L., Paleari, L., Basso, G., Mangioni, M., Fidanza, V., Albini, A., Croce, C.M., Levi, G., Brigati, C. J. Leukoc. Biol. (2003) [Pubmed]
  3. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Anderson, S.A., Eisenstat, D.D., Shi, L., Rubenstein, J.L. Science (1997) [Pubmed]
  4. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Feng, J., Bi, C., Clark, B.S., Mady, R., Shah, P., Kohtz, J.D. Genes Dev. (2006) [Pubmed]
  5. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Cobos, I., Calcagnotto, M.E., Vilaythong, A.J., Thwin, M.T., Noebels, J.L., Baraban, S.C., Rubenstein, J.L. Nat. Neurosci. (2005) [Pubmed]
  6. Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons. Pleasure, S.J., Anderson, S., Hevner, R., Bagri, A., Marin, O., Lowenstein, D.H., Rubenstein, J.L. Neuron (2000) [Pubmed]
  7. Regulatory roles of conserved intergenic domains in vertebrate Dlx bigene clusters. Ghanem, N., Jarinova, O., Amores, A., Long, Q., Hatch, G., Park, B.K., Rubenstein, J.L., Ekker, M. Genome Res. (2003) [Pubmed]
  8. Expression of Dlx and Lhx family homeobox genes in fetal thymus and thymocytes. Woodside, K.J., Shen, H., Muntzel, C., Daller, J.A., Sommers, C.L., Love, P.E. Gene Expr. Patterns (2004) [Pubmed]
  9. Intergenic enhancers with distinct activities regulate Dlx gene expression in the mesenchyme of the branchial arches. Park, B.K., Sperber, S.M., Choudhury, A., Ghanem, N., Hatch, G.T., Sharpe, P.T., Thomas, B.L., Ekker, M. Dev. Biol. (2004) [Pubmed]
  10. Dlx1, Dlx2, Pax6, Brn3b, and Chx10 homeobox gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina. de Melo, J., Qiu, X., Du, G., Cristante, L., Eisenstat, D.D. J. Comp. Neurol. (2003) [Pubmed]
  11. Identification and characterization of a novel transcript down-regulated in Dlx1/Dlx2 and up-regulated in Pax6 mutant telencephalon. Faedo, A., Quinn, J.C., Stoney, P., Long, J.E., Dye, C., Zollo, M., Rubenstein, J.L., Price, D.J., Bulfone, A. Dev. Dyn. (2004) [Pubmed]
  12. Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic ventral lateral geniculate nuclear formation. Kitamura, K., Miura, H., Yanazawa, M., Miyashita, T., Kato, K. Mech. Dev. (1997) [Pubmed]
  13. Expression of regulatory genes during differentiation of thalamic nuclei in mouse and monkey. Jones, E.G., Rubenstein, J.L. J. Comp. Neurol. (2004) [Pubmed]
  14. Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation. Saino-Saito, S., Berlin, R., Baker, H. J. Comp. Neurol. (2003) [Pubmed]
  15. Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Liu, J.K., Ghattas, I., Liu, S., Chen, S., Rubenstein, J.L. Dev. Dyn. (1997) [Pubmed]
  16. Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. Stühmer, T., Anderson, S.A., Ekker, M., Rubenstein, J.L. Development (2002) [Pubmed]
  17. Origins of cortical interneuron subtypes. Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J.L., Anderson, S.A. J. Neurosci. (2004) [Pubmed]
  18. The vertebrate ortholog of Aristaless is regulated by Dlx genes in the developing forebrain. Cobos, I., Broccoli, V., Rubenstein, J.L. J. Comp. Neurol. (2005) [Pubmed]
  19. Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Petryniak, M.A., Potter, G.B., Rowitch, D.H., Rubenstein, J.L. Neuron (2007) [Pubmed]
  20. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. Bulfone, A., Puelles, L., Porteus, M.H., Frohman, M.A., Martin, G.R., Rubenstein, J.L. J. Neurosci. (1993) [Pubmed]
  21. Dlx transcription factors regulate differentiation of dopaminergic neurons of the ventral thalamus. Andrews, G.L., Yun, K., Rubenstein, J.L., Mastick, G.S. Mol. Cell. Neurosci. (2003) [Pubmed]
  22. Identification of a direct Dlx homeodomain target in the developing mouse forebrain and retina by optimization of chromatin immunoprecipitation. Zhou, Q.P., Le, T.N., Qiu, X., Spencer, V., de Melo, J., Du, G., Plews, M., Fonseca, M., Sun, J.M., Davie, J.R., Eisenstat, D.D. Nucleic Acids Res. (2004) [Pubmed]
  23. Decreased thalamic expression of the homeobox gene DLX1 in psychosis. Kromkamp, M., Uylings, H.B., Smidt, M.P., Hellemons, A.J., Burbach, J.P., Kahn, R.S. Arch. Gen. Psychiatry (2003) [Pubmed]
  24. Expression from a Dlx gene enhancer marks adult mouse cortical GABAergic neurons. Stühmer, T., Puelles, L., Ekker, M., Rubenstein, J.L. Cereb. Cortex (2002) [Pubmed]
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