DLX gene family

In evolutionary developmental biology, DLX is a family of homeodomain transcription factors which are related to the Drosophila distal-less (Dll) gene.[1]

Distal-less itself, and its homologues, is involved in limb development in most of the major phyla, including vertebrates — suggesting that it was involved in appendage growth in an early bilaterial ancestor.[2]

The family has been related to a number of developmental features.[3][4] The family seems to be well preserved across species.[5]

Known members of the family include DLX1 to DLX6. They form two-gene clusters (bigene clusters) with each other. There are DLX1-DLX2, DLX3-DLX4, DLX5-DLX6 clusters in vertebrates. Each of those are linked to a specific Hox gene cluster. In higher fishes, like Zebrafish, there are a couple of additional DLX genes, DLX5 and DLX8. In zebrafish the orthologous genes to vertebrate DLX5-DLX6 are DLX4 and DLX6, which form a bigene cluster in zebrafish. These additional genes are not linked with each other, or any other DLX gene.

DLX4, DLX7, DLX8 and DLX9 are the same gene in vertebrates. They're named differently, because every time the same gene was found, the researchers thought they had found a new gene.

DLX genes are involved in craniofacial morphogenesis [6][7][8] and the tangential migration of interneurons from the subpallium to the pallium during vertebrate brain development.[9] It has been suggested that DLX promotes the migration of interneurons by repressing a set of proteins that are normally expressed in terminally differentiated neurons and act to promote the outgrowth of dendrites and axons.[10] Mice lacking DLX1 exhibit electrophysiological and histological evidence consistent with delayed-onset epilepsy.[11]

DLX2 has been associated with a number of areas including development of the zona limitans intrathalamica and the prethalamus.

DLX5 and DLX6 genes are necessary for normal formation of the mandible in vertebrates.[6][7]

DLX7 is expressed in bone marrow.[12]


  1. Panganiban, G.; Rubenstein, J. L. (2002). "Developmental functions of the Distal-less/Dlx homeobox genes". Development (Cambridge, England). 129 (19): 4371–4386. PMID 12223397.
  2. Panganiban, G.; Irvine, S. M.; Lowe, C.; Roehl, H.; Corley, L. S.; Sherbon, B.; Grenier, J. K.; Fallon, J. F.; Kimble, J.; Walker, M.; Wray, G. A.; Swalla, B. J.; Martindale, M. Q.; Carroll, S. B. (1997). "The origin and evolution of animal appendages". Proceedings of the National Academy of Sciences of the United States of America. 94 (10): 5162–5166. doi:10.1073/pnas.94.10.5162. PMC 24649Freely accessible. PMID 9144208.
  3. Vieux-Rochas M.; Coen L.; Sato T.; Kurihara Y.; Gitton Y.; Barbier O.; Le Blay K.; Merlo G.R.; Ekker M.; Kurihara H.; Janvier P.; Levi G. (June 2007). Heisenberg, Carl-Philipp, ed. "Molecular Dynamics of Retinoic Acid-Induced Craniofacial Malformations: Implications for the Origin of Gnathostome Jaws". PLoS ONE. 2 (6): e510. doi:10.1371/journal.pone.0000510. PMC 1876820Freely accessible. PMID 17551590.
  4. Vieux-Rochas M.; Bouhali K.; Baudry S.; Fontaine A.; Coen L.; Levi G. (July 2010). "Irreversible Effects of Retinoic Acid Pulse on Xenopus Jaw Morphogenesis: New Insight Into Cranial Neural Crest Specification". Birth Defects Research (Part B). 89 (6): 493–503. doi:10.1002/bdrb.20269.
  5. Stock DW; Ellies DL; Zhao Z; Ekker M; Ruddle FH; Weiss KM. (October 1996). "The evolution of the vertebrate DLX gene family". Proc Natl Acad Sci U S A. 93 (20): 10858–10863. doi:10.1073/pnas.93.20.10858. PMC 38247Freely accessible. PMID 8855272.
  6. 1 2 Beverdam A; Merlo G.R.; Paleari L.; Mantero S.; Genova F.; Barbieri O.; Janvier P.; Levi G. (August 2002). "Jaw Transformation With Gain of Symmetry After DLX5/DLX6 Inactivation: Mirror of the Past?". Genesis. 34 (4): 221–227. doi:10.1002/gene.10156. PMID 12434331.
  7. 1 2 Depew MJ; Lufkin T; Rubenstein JL (October 2002). "Specification of jaw subdivisions by DLX genes". Science. 298 (5592): 381–385. doi:10.1126/science.1075703. PMID 12193642.
  8. Vieux-Rochas M.; Mantero S.; Heude E.; Barbieri O.; Astigiano S.; Couly G.; Kurihara H.; Levi G.; Merlo G.R. (March 2010). "Spatio-Temporal Dynamics of Gene Expression of the Edn1-DLX5/6 Pathway During Development of the Lower Jaw". Genesis. 48 (6): 362–373. doi:10.1002/dvg.20625.
  9. Anderson SA; Eisenstat DD; Shi L; Rubenstein JL. (October 1997). "Interneuron migration from basal forebrain to neocortex: dependence on DLX genes". Science. 278 (5337): 474–476. doi:10.1126/science.278.5337.474. PMID 9334308.
  10. Cobos I; Borello U; Rubenstein JL. (June 2007). "DLX transcription factors promote migration through repression of axon and dendrite growth". Neuron. 54 (6): 873–888. doi:10.1016/j.neuron.2007.05.024. PMID 17582329.
  11. Cobos I; Calcagnotto ME; Vilaythong AJ; Thwin MT; Noebels JL; Baraban SC; Rubenstein JL. (August 2005). "Mice lacking DLX1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy". Nat Neurosci. 8 (8): 1059–1068. doi:10.1038/nn1499. PMID 16007083.
  12. Takashi Shimamoto; Shuji Nakamura; Jacques Bollekens; Frank H. Ruddle; Kenichi Takeshita (April 1997). "Inhibition of DLX-7 homeobox gene causes decreased expression of GATA-1 and c-myc genes and apoptosis". Proc Natl Acad Sci U S A. 94 (7): 3245–3249. doi:10.1073/pnas.94.7.3245. PMC 20354Freely accessible. PMID 9096378.
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