DLX gene family

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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]

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<span class="mw-page-title-main">Homeobox</span> DNA pattern affecting anatomy development

A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism.

The ParaHox gene cluster is an array of homeobox genes from the Gsx, Xlox (Pdx) and Cdx gene families.

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

<i>Antennapedia</i> Hox gene

Antennapedia is a Hox gene first discovered in Drosophila which controls the formation of legs during development. Loss-of-function mutations in the regulatory region of this gene result in the development of the second leg pair into ectopic antennae. By contrast gain-of-function alleles convert antennae into ectopic legs.

<span class="mw-page-title-main">Otic vesicle</span> Two sac-like invaginations formed and subsequently closed off during embryonic development

Otic vesicle, or auditory vesicle, consists of either of the two sac-like invaginations formed and subsequently closed off during embryonic development. It is part of the neural ectoderm, which will develop into the membranous labyrinth of the inner ear. This labyrinth is a continuous epithelium, giving rise to the vestibular system and auditory components of the inner ear. During the earlier stages of embryogenesis, the otic placode invaginates to produce the otic cup. Thereafter, the otic cup closes off, creating the otic vesicle. Once formed, the otic vesicle will reside next to the neural tube medially, and on the lateral side will be paraxial mesoderm. Neural crest cells will migrate rostral and caudal to the placode.

<span class="mw-page-title-main">Msh homeobox 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">HOXB5</span> Protein-coding gene in humans

Homeobox protein Hox-B5 is a protein that in humans is encoded by the HOXB5 gene.

<span class="mw-page-title-main">HOXC8</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-C8 is a protein that in humans is encoded by the HOXC8 gene.

<span class="mw-page-title-main">HOXD13</span> Protein

Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene. This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms.

<span class="mw-page-title-main">DLX5</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-5 is a protein that in humans is encoded by the distal-less homeobox 5 gene, or DLX5 gene. DLX5 is a member of DLX gene family.

<span class="mw-page-title-main">DLX3</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-3 is a protein that in humans is encoded by the DLX3 gene.

<span class="mw-page-title-main">DLX4</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-4 is a protein that in humans is encoded by the DLX4 gene.

<span class="mw-page-title-main">HOXC5</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-C5 is a protein that in humans is encoded by the HOXC5 gene.

<span class="mw-page-title-main">DLX2</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-2 is a protein that in humans is encoded by the DLX2 gene.

<span class="mw-page-title-main">HOXC11</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-C11 is a protein that in humans is encoded by the HOXC11 gene.

<span class="mw-page-title-main">DLX1</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-1 is a protein that in humans is encoded by the DLX1 gene.

<span class="mw-page-title-main">DLX6</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-6 is a protein that in humans is encoded by the DLX6 gene.

<span class="mw-page-title-main">DBX2</span> Protein-coding gene in humans

Homeobox protein DBX2, also known as developing brain homeobox protein 2, is a protein that in humans is encoded by the DBX2 gene. DBX2 plays an important role in the development of the central nervous system, specifically in the development of the neural tube and brain. DBX2 is located on chromosome 12 and is approximately 36,000 base pairs long. DBX2 is predicted to enable DNA-binding transcription activity as well as being involved in the regulation of transcription by RNA polymerase II.

<span class="mw-page-title-main">DLX6-AS1</span>

DLX6 antisense RNA 1 (DLX6-AS1) is a developmentally-regulated long non-coding RNA. In rats, it is expressed in neurons in the subventricular zone of the developing forebrain. Its expression is linked to that of the Shh and DLX families of genes, which are important in ventral forebrain and craniofacial development. An alternatively spliced form of DLX6-AS1, DLX6-AS2, forms a stable complex with the Dlx-2 protein. This complex activates transcription of Dlx-5 and Dlx-6.

References

  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.
  3. 1 2 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.
  6. ↑ "Entrez Gene: DLX4 distal-less homeobox 4".
  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.
  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.
  9. ↑ Vieux-Rochas M, Coen L, Sato T, Kurihara Y, Gitton Y, Barbieri O, et al. (June 2007). Heisenberg C (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. Open Access logo PLoS transparent.svg
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
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