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Gene Review

DLX2  -  distal-less homeobox 2

Homo sapiens

Synonyms: Homeobox protein DLX-2, TES-1, TES1
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Disease relevance of DLX2

  • In leukemic patients affected by the t(4;11)(q21;q23) chromosomal abnormality, the expression of DLX2, DLX3, and DLX4 was virtually abrogated [1].
  • In addition, the initial assignments into sFv pools based on phage ELISA readings allowed the segregation of individual anti-TES1 sFvs into discrete or minimally overlapping intrabody pools [2].
  • Establishment and characterization of human immature teratoma cell line (TES-1) [3].

High impact information on DLX2

  • Upon integration into the striatal GZ, cortical stem cells down-regulate Emx1 and up-regulate Dlx2, which is a homeobox gene characteristic of the developing striatum and striatal neural stem cells [4].
  • Altogether these data suggest a molecular mechanism for tooth development involving Dlx2 gene expression in ARS patients [5].
  • From isolated clones in the 30N and 60N size groups, two predominant RNA sequences, TES1 (30N) and TES33 (60N), have been shown to catalyze the synthesis of different thioesters using various acyl adenylates as the substrates [6].
  • A zebrafish forebrain-specific zinc finger gene can induce ectopic dlx2 and dlx6 expression [7].
  • We report the expression of neurexin 1, Neuro D1, dlx1, and dlx2 in untreated and cAMP treated epithelial prostate cells [8].

Biological context of DLX2


Anatomical context of DLX2

  • Using cell-specific markers and antibodies to ventral homeodomain transcription factors, NKX2.1 and DLX2, we show here that a subpopulation of early oligodendrocyte progenitor cells (OPCs) in the human telencephalon may originate in the ganglionic eminence (GE) [13].
  • Dlx2 activates the Msx2 promoter in several cell lines and binds DNA as a monomer and dimer [11].
  • Immunohistochemical analysis revealed that necdin was coexpressed with Dlx2, Dlx5, or MAGE-D1 in a subpopulation of embryonic forebrain cells [14].
  • Lateral cells appearing to emanate from r4 express both hoxb2 and dlx2, suggesting that they are neural crest [15].
  • PITX2 binds to bicoid and bicoid-like elements in the Dlx2 promoter and activates this promoter 45-fold in CHO cells [16].

Other interactions of DLX2


Analytical, diagnostic and therapeutic context of DLX2

  • To identify co-factors that regulate DLX function we utilized the yeast two-hybrid assay, and found a DLX interacting protein (DIP2) which binds to the N-terminal region of DLX2 via a PDZ domain [17].
  • Co-immunoprecipitation and protein pull-down experiments demonstrate Lef-1 physically interacts with Dlx2 [11].


  1. 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]
  2. Direct phage to intrabody screening (DPIS): demonstration by isolation of cytosolic intrabodies against the TES1 site of Epstein Barr virus latent membrane protein 1 (LMP1) that block NF-kappaB transactivation. Gennari, F., Mehta, S., Wang, Y., St Clair Tallarico, A., Palu, G., Marasco, W.A. J. Mol. Biol. (2004) [Pubmed]
  3. Establishment and characterization of human immature teratoma cell line (TES-1). Iida, M., Doi, H., Asamoto, S., Sugiyama, H., Sakagami, H., Shioda, S., Kuribayashi, N., Takeda, M., Okamura, Y., Matsumoto, K. Anticancer Res. (1999) [Pubmed]
  4. Embryonic cortical neural stem cells migrate ventrally and persist as postnatal striatal stem cells. Willaime-Morawek, S., Seaberg, R.M., Batista, C., Labb??, E., Attisano, L., Gorski, J.A., Jones, K.R., Kam, A., Morshead, C.M., van der Kooy, D. J. Cell Biol. (2006) [Pubmed]
  5. A molecular basis for differential developmental anomalies in Axenfeld-Rieger syndrome. Espinoza, H.M., Cox, C.J., Semina, E.V., Amendt, B.A. Hum. Mol. Genet. (2002) [Pubmed]
  6. RNA-catalyzed thioester synthesis. Coleman, T.M., Huang, F. Chem. Biol. (2002) [Pubmed]
  7. A zebrafish forebrain-specific zinc finger gene can induce ectopic dlx2 and dlx6 expression. Yang, Z., Liu, N., Lin, S. Dev. Biol. (2001) [Pubmed]
  8. cAMP induced modifications of HOX D gene expression in prostate cells allow the identification of a chromosomal area involved in vivo with neuroendocrine differentiation of human advanced prostate cancers. Cantile, M., Kisslinger, A., Cindolo, L., Schiavo, G., D'Antò, V., Franco, R., Altieri, V., Gallo, A., Villacci, A., Tramontano, D., Cillo, C. J. Cell. Physiol. (2005) [Pubmed]
  9. Induction of apoptosis by fenretinide in tumor cell lines correlates with DLX2, DLX3 and DLX4 gene expression. Ferrari, N., Paleari, L., Palmisano, G.L., Tammaro, P., Levi, G., Albini, A., Brigati, C. Oncol. Rep. (2003) [Pubmed]
  10. DLX2 (TES1), a homeobox gene of the Distal-less family, assigned to conserved regions on human and mouse chromosomes 2. Ozçelik, T., Porteus, M.H., Rubenstein, J.L., Francke, U. Genomics (1992) [Pubmed]
  11. Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2. Diamond, E., Amen, M., Hu, Q., Espinoza, H.M., Amendt, B.A. Nucleic Acids Res. (2006) [Pubmed]
  12. Transcriptional regulation of BMP-2 activated genes in osteoblasts using gene expression microarray analysis: role of Dlx2 and Dlx5 transcription factors. Harris, S.E., Guo, D., Harris, M.A., Krishnaswamy, A., Lichtler, A. Front. Biosci. (2003) [Pubmed]
  13. Early oligodendrocyte progenitor cells in the human fetal telencephalon. Rakic, S., Zecevic, N. Glia (2003) [Pubmed]
  14. Necdin promotes GABAergic neuron differentiation in cooperation with Dlx homeodomain proteins. Kuwajima, T., Nishimura, I., Yoshikawa, K. J. Neurosci. (2006) [Pubmed]
  15. Ectopic expression of hoxb2 after retinoic acid treatment or mRNA injection: disruption of hindbrain and craniofacial morphogenesis in zebrafish embryos. Yan, Y.L., Jowett, T., Postlethwait, J.H. Dev. Dyn. (1998) [Pubmed]
  16. Antagonistic regulation of Dlx2 expression by PITX2 and Msx2: implications for tooth development. Green, P.D., Hjalt, T.A., Kirk, D.E., Sutherland, L.B., Thomas, B.L., Sharpe, P.T., Snead, M.L., Murray, J.C., Russo, A.F., Amendt, B.A. Gene Expr. (2001) [Pubmed]
  17. Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins. Yu, G., Zerucha, T., Ekker, M., Rubenstein, J.L. Brain Res. Dev. Brain Res. (2001) [Pubmed]
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