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Genes in the DLX family encode homeodomain transcription factors related to the Drosophila distal-less (Dll) gene.^[1] The family has been related to a number of developmental features such as jaws and limbs. The family seems to be well preserved across species.^[2] As DLX/Dll are involved in limb development in most of the major phyla, including vertebrates, it has been suggested that Dll was involved in appendage growth in an early bilaterial ancestor.^[3]

Six members of the family are found in human and mice, numbered DLX1 to DLX6. They form two-gene clusters (bigene clusters) with each other. There are DLX1-DLX2, DLX3-DLX4, DLX5-DLX6 clusters in vertebrates, linked to Hox gene clusters HOXD, HOXB, and HOXA respectively.^[4]

In higher fishes like the zebrafish, there are two additional DLX genes, dlx2b (dlx5) and dlx4a (dlx8).^[5] These additional genes are not linked with each other, or any other DLX gene. All six other genes remain in bigene clusters.

DLX4, DLX7, DLX8 and DLX9 are the same gene in vertebrates.^[6] They are named differently because every time the same gene was found, the researchers thought they had found a new gene.^[7]^[8]

Function

DLX genes, like distal-less, are involved in limb development in most of the major phyla.^[3]

DLX genes are involved in craniofacial morphogenesis^[9]^[10] and the tangential migration of interneurons from the subpallium to the pallium during vertebrate brain development.^[11] 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.^[12] Mice lacking DLX1 exhibit electrophysiological and histological evidence consistent with delayed-onset epilepsy.^[13]

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

DLX4 (DLX7) is expressed in bone marrow.^[14]

DLX5 and DLX6 genes are necessary for normal formation of the mandible in vertebrates.^[15]^[16]^[17]

References

^ Panganiban G, Rubenstein JL (October 2002). "Developmental functions of the Distal-less/Dlx homeobox genes". Development. 129 (19): 4371–86. doi:10.1242/dev.129.19.4371. PMID 12223397.
^ Stock DW, Ellies DL, Zhao Z, Ekker M, Ruddle FH, Weiss KM (October 1996). "The evolution of the vertebrate Dlx gene family". Proceedings of the National Academy of Sciences of the United States of America. 93 (20): 10858–63. Bibcode:1996PNAS...9310858S. doi:10.1073/pnas.93.20.10858. PMC 38247. PMID 8855272.
^ ^a ^b Panganiban G, Irvine SM, Lowe C, Roehl H, Corley LS, Sherbon B, et al. (May 1997). "The origin and evolution of animal appendages". Proceedings of the National Academy of Sciences of the United States of America. 94 (10): 5162–6. Bibcode:1997PNAS...94.5162P. doi:10.1073/pnas.94.10.5162. PMC 24649. PMID 9144208.
^ Stock DW, Ellies DL, Zhao Z, Ekker M, Ruddle FH, Weiss KM (October 1996). "The evolution of the vertebrate Dlx gene family". Proceedings of the National Academy of Sciences of the United States of America. 93 (20): 10858–63. Bibcode:1996PNAS...9310858S. doi:10.1073/pnas.93.20.10858. PMC 38247. PMID 8855272.
^ "dlx AND(Danio rerio[organism])". NCBI Gene. Retrieved 12 March 2018.
^ "Entrez Gene: DLX4 distal-less homeobox 4".
^ Nakamura S, Stock DW, Wydner KL, Bollekens JA, Takeshita K, Nagai BM, et al. (December 1996). "Genomic analysis of a new mammalian distal-less gene: Dlx7". Genomics. 38 (3): 314–24. doi:10.1006/geno.1996.0634. PMID 8975708.
^ Quinn LM, Johnson BV, Nicholl J, Sutherland GR, Kalionis B (March 1997). "Isolation and identification of homeobox genes from the human placenta including a novel member of the Distal-less family, DLX4". Gene. 187 (1): 55–61. doi:10.1016/S0378-1119(96)00706-8. PMID 9073066. We originally submitted the cDNA sequence to the Genbank database as DLX8 (Accession number U31762) even though human DLX4 or DLX7 had not been identified. [...] This new Distal-less gene could not be considered the human homologue of murine Dlx4 or Dlx7 because the homeodomain sequences were too diverged.
^ Vieux-Rochas M, Coen L, Sato T, Kurihara Y, Gitton Y, Barbieri O, et al. (June 2007). Heisenberg CP (ed.). "Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws". PLOS ONE. 2 (6): e510. Bibcode:2007PLoSO...2..510V. doi:10.1371/journal.pone.0000510. PMC 1876820. PMID 17551590.
^ Vieux-Rochas M, Bouhali K, Baudry S, Fontaine A, Coen L, Levi G (December 2010). "Irreversible effects of retinoic acid pulse on Xenopus jaw morphogenesis: new insight into cranial neural crest specification". Birth Defects Research Part B: Developmental and Reproductive Toxicology. 89 (6): 493–503. doi:10.1002/bdrb.20269. PMID 21086490.
^ Anderson SA, Eisenstat DD, Shi L, Rubenstein JL (October 1997). "Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes". Science. 278 (5337): 474–6. doi:10.1126/science.278.5337.474. PMID 9334308.
^ Cobos I, Borello U, Rubenstein JL (June 2007). "Dlx transcription factors promote migration through repression of axon and dendrite growth". Neuron. 54 (6): 873–88. doi:10.1016/j.neuron.2007.05.024. PMC 4921237. PMID 17582329.
^ 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". Nature Neuroscience. 8 (8): 1059–68. doi:10.1038/nn1499. PMID 16007083. S2CID 883159.
^ Shimamoto T, Nakamura S, Bollekens J, Ruddle FH, Takeshita K (April 1997). "Inhibition of DLX-7 homeobox gene causes decreased expression of GATA-1 and c-myc genes and apoptosis". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3245–9. Bibcode:1997PNAS...94.3245S. doi:10.1073/pnas.94.7.3245. PMC 20354. PMID 9096378.
^ Beverdam A, Merlo GR, Paleari L, Mantero S, Genova F, Barbieri O, et al. (December 2002). "Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: mirror of the past?". Genesis. 34 (4): 221–7. doi:10.1002/gene.10156. hdl:2318/87307. PMID 12434331. S2CID 19592597.
^ Depew MJ, Lufkin T, Rubenstein JL (October 2002). "Specification of jaw subdivisions by Dlx genes". Science. 298 (5592): 381–5. doi:10.1126/science.1075703. PMID 12193642. S2CID 10274300.
^ Vieux-Rochas M, Mantero S, Heude E, Barbieri O, Astigiano S, Couly G, et al. (June 2010). "Spatio-temporal dynamics of gene expression of the Edn1-Dlx5/6 pathway during development of the lower jaw" (PDF). Genesis. 48 (6): 262–373. doi:10.1002/dvg.20625. hdl:2318/79557. PMID 20333701. S2CID 1050844.