DLX gene family

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]

^ 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.
^ 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.

[1] 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.

[2] 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.

[limb-urbilateria-3] 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.

[4] 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.

[5] "dlx AND(Danio rerio[organism])". NCBI Gene. Retrieved 12 March 2018.

[entrez-dlx4-6] "Entrez Gene: DLX4 distal-less homeobox 4".

[dlx7-new-7] 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.

[dlx4-new-8] 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.

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