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Proc Natl Acad Sci U S A. Oct 1, 1996; 93(20): 10858–10863.
PMCID: PMC38247

The evolution of the vertebrate Dlx gene family.

Abstract

The vertebrate Dlx gene family consists of homeobox-containing transcription factors distributed in pairs on the same chromosomes as the Hox genes. To investigate the evolutionary history of Dlx genes, we have cloned five new zebrafish family members and have provided additional sequence information for two mouse genes. Phylogenetic analyses of Dlx gene sequences considered in the context of their chromosomal arrangements suggest that an initial tandem duplication produced a linked pair of Dlx genes after the divergence of chordates and arthropods but prior to the divergence of tunicates and vertebrates. This pair of Dlx genes was then duplicated in the chromosomal events that led to the four clusters of Hox genes characteristic of bony fish and tetrapods. It is possible that a pair of Dlx genes linked to the Hoxc cluster has been lost from mammals. We were unable to distinguish between independent duplication and retention of the ancestral state of bony vertebrates to explain the presence of a greater number of Dlx genes in zebrafish than mammals. Determination of the linkage relationship of these additional zebrafish Dlx genes to Hox clusters should help resolve this issue.

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  • Gaunt SJ. Expression patterns of mouse Hox genes: clues to an understanding of developmental and evolutionary strategies. Bioessays. 1991 Oct;13(10):505–513. [PubMed]
  • Hunt P, Krumlauf R. Hox codes and positional specification in vertebrate embryonic axes. Annu Rev Cell Biol. 1992;8:227–256. [PubMed]
  • Krumlauf R. Hox genes in vertebrate development. Cell. 1994 Jul 29;78(2):191–201. [PubMed]
  • Ruddle FH, Bartels JL, Bentley KL, Kappen C, Murtha MT, Pendleton JW. Evolution of Hox genes. Annu Rev Genet. 1994;28:423–442. [PubMed]
  • Ruddle FH, Bentley KL, Murtha MT, Risch N. Gene loss and gain in the evolution of the vertebrates. Dev Suppl. 1994:155–161. [PubMed]
  • Holland PW, Garcia-Fernàndez J. Hox genes and chordate evolution. Dev Biol. 1996 Feb 1;173(2):382–395. [PubMed]
  • Schughart K, Kappen C, Ruddle FH. Duplication of large genomic regions during the evolution of vertebrate homeobox genes. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7067–7071. [PMC free article] [PubMed]
  • Kappen C, Schughart K, Ruddle FH. Two steps in the evolution of Antennapedia-class vertebrate homeobox genes. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5459–5463. [PMC free article] [PubMed]
  • Pendleton JW, Nagai BK, Murtha MT, Ruddle FH. Expansion of the Hox gene family and the evolution of chordates. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6300–6304. [PMC free article] [PubMed]
  • Ozçelik T, Porteus MH, Rubenstein JL, Francke U. DLX2 (TES1), a homeobox gene of the Distal-less family, assigned to conserved regions on human and mouse chromosomes 2. Genomics. 1992 Aug;13(4):1157–1161. [PubMed]
  • Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K, et al. Cloning and characterization of two members of the vertebrate Dlx gene family. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2250–2254. [PMC free article] [PubMed]
  • Rossi E, Faiella A, Zeviani M, Labeit S, Floridia G, Brunelli S, Cammarata M, Boncinelli E, Zuffardi O. Order of six loci at 2q24-q31 and orientation of the HOXD locus. Genomics. 1994 Nov 1;24(1):34–40. [PubMed]
  • Scherer SW, Heng HH, Robinson GW, Mahon KA, Evans JP, Tsui LC. Assignment of the human homolog of mouse Dlx3 to chromosome 17q21.3-q22 by analysis of somatic cell hybrids and fluorescence in situ hybridization. Mamm Genome. 1995 Apr;6(4):310–311. [PubMed]
  • Cohen SM, Brönner G, Küttner F, Jürgens G, Jäckle H. Distal-less encodes a homoeodomain protein required for limb development in Drosophila. Nature. 1989 Mar 30;338(6214):432–434. [PubMed]
  • Akimenko MA, Ekker M, Wegner J, Lin W, Westerfield M. Combinatorial expression of three zebrafish genes related to distal-less: part of a homeobox gene code for the head. J Neurosci. 1994 Jun;14(6):3475–3486. [PubMed]
  • Beauchemin M, Savard P. Two distal-less related homeobox-containing genes expressed in regeneration blastemas of the newt. Dev Biol. 1992 Nov;154(1):55–65. [PubMed]
  • Asano M, Emori Y, Saigo K, Shiokawa K. Isolation and characterization of a Xenopus cDNA which encodes a homeodomain highly homologous to Drosophila Distal-less. J Biol Chem. 1992 Mar 15;267(8):5044–5047. [PubMed]
  • Papalopulu N, Kintner C. Xenopus Distal-less related homeobox genes are expressed in the developing forebrain and are induced by planar signals. Development. 1993 Mar;117(3):961–975. [PubMed]
  • Dirksen ML, Mathers P, Jamrich M. Expression of a Xenopus Distal-less homeobox gene involved in forebrain and cranio-facial development. Mech Dev. 1993 May;41(2-3):121–128. [PubMed]
  • Dirksen ML, Morasso MI, Sargent TD, Jamrich M. Differential expression of a Distal-less homeobox gene Xdll-2 in ectodermal cell lineages. Mech Dev. 1994 Apr;46(1):63–70. [PubMed]
  • Robinson GW, Wray S, Mahon KA. Spatially restricted expression of a member of a new family of murine Distal-less homeobox genes in the developing forebrain. New Biol. 1991 Dec;3(12):1183–1194. [PubMed]
  • Price M, Lemaistre M, Pischetola M, Di Lauro R, Duboule D. A mouse gene related to Distal-less shows a restricted expression in the developing forebrain. Nature. 1991 Jun 27;351(6329):748–751. [PubMed]
  • Porteus MH, Bulfone A, Ciaranello RD, Rubenstein JL. Isolation and characterization of a novel cDNA clone encoding a homeodomain that is developmentally regulated in the ventral forebrain. Neuron. 1991 Aug;7(2):221–229. [PubMed]
  • Robinson GW, Mahon KA. Differential and overlapping expression domains of Dlx-2 and Dlx-3 suggest distinct roles for Distal-less homeobox genes in craniofacial development. Mech Dev. 1994 Dec;48(3):199–215. [PubMed]
  • Weiss KM, Ruddle FH, Bollekens J. Dlx and other homeobox genes in the morphological development of the dentition. Connect Tissue Res. 1995;32(1-4):35–40. [PubMed]
  • Selski DJ, Thomas NE, Coleman PD, Rogers KE. The human brain homeogene, DLX-2: cDNA sequence and alignment with the murine homologue. Gene. 1993 Oct 15;132(2):301–303. [PubMed]
  • Qiu M, Bulfone A, Martinez S, Meneses JJ, Shimamura K, Pedersen RA, Rubenstein JL. Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. Genes Dev. 1995 Oct 15;9(20):2523–2538. [PubMed]
  • Di Gregorio A, Spagnuolo A, Ristoratore F, Pischetola M, Aniello F, Branno M, Cariello L, Di Lauro R. Cloning of ascidian homeobox genes provides evidence for a primordial chordate cluster. Gene. 1995 Apr 24;156(2):253–257. [PubMed]
  • Ferrari D, Sumoy L, Gannon J, Sun H, Brown AM, Upholt WB, Kosher RA. The expression pattern of the Distal-less homeobox-containing gene Dlx-5 in the developing chick limb bud suggests its involvement in apical ectodermal ridge activity, pattern formation, and cartilage differentiation. Mech Dev. 1995 Aug;52(2-3):257–264. [PubMed]
  • Zhao GQ, Zhao S, Zhou X, Eberspaecher H, Solursh M, de Crombrugghe B. rDlx, a novel distal-less-like homeoprotein is expressed in developing cartilages and discrete neuronal tissues. Dev Biol. 1994 Jul;164(1):37–51. [PubMed]
  • Holland PW. Cloning and evolutionary analysis of msh-like homeobox genes from mouse, zebrafish and ascidian. Gene. 1991 Feb 15;98(2):253–257. [PubMed]
  • Tissier-Seta JP, Mucchielli ML, Mark M, Mattei MG, Goridis C, Brunet JF. Barx1, a new mouse homeodomain transcription factor expressed in cranio-facial ectomesenchyme and the stomach. Mech Dev. 1995 May;51(1):3–15. [PubMed]
  • Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. [PMC free article] [PubMed]
  • Ekker M, Speevak MD, Martin CC, Joly L, Giroux G, Chevrette M. Stable transfer of zebrafish chromosome segments into mouse cells. Genomics. 1996 Apr 1;33(1):57–64. [PubMed]
  • Wang BB, Müller-Immergluck MM, Austin J, Robinson NT, Chisholm A, Kenyon C. A homeotic gene cluster patterns the anteroposterior body axis of C. elegans. Cell. 1993 Jul 16;74(1):29–42. [PubMed]
  • Wilson R, Ainscough R, Anderson K, Baynes C, Berks M, Bonfield J, Burton J, Connell M, Copsey T, Cooper J, et al. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994 Mar 3;368(6466):32–38. [PubMed]
  • van der Hoeven F, Sordino P, Fraudeau N, Izpisúa-Belmonte JC, Duboule D. Teleost HoxD and HoxA genes: comparison with tetrapods and functional evolution of the HOXD complex. Mech Dev. 1996 Jan;54(1):9–21. [PubMed]
  • Felsenstein J. Phylogenies from molecular sequences: inference and reliability. Annu Rev Genet. 1988;22:521–565. [PubMed]
  • Akimenko MA, Johnson SL, Westerfield M, Ekker M. Differential induction of four msx homeobox genes during fin development and regeneration in zebrafish. Development. 1995 Feb;121(2):347–357. [PubMed]
  • Ekker SC, Ungar AR, Greenstein P, von Kessler DP, Porter JA, Moon RT, Beachy PA. Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr Biol. 1995 Aug 1;5(8):944–955. [PubMed]
  • Joly JS, Joly C, Schulte-Merker S, Boulekbache H, Condamine H. The ventral and posterior expression of the zebrafish homeobox gene eve1 is perturbed in dorsalized and mutant embryos. Development. 1993 Dec;119(4):1261–1275. [PubMed]
  • Wolf U, Ritter H, Atkin NB, Ohno S. Polyploidization in the fish family Cyprinidae, order Cypriniformes. I. DNA-content and chromosome sets in various species of Cyprinidae. Humangenetik. 1969;7(3):240–244. [PubMed]
  • Endo A, Ingalls TH. Chromosomes of the zebra fish. A model for cytogenetic, embryologic, and ecologic study. J Hered. 1968 Nov-Dec;59(6):382–384. [PubMed]
  • Dollé P, Fraulob V, Duboule D. Developmental expression of the mouse Evx-2 gene: relationship with the evolution of the HOM/Hox complex. Dev Suppl. 1994:143–153. [PubMed]
  • Bulfone A, Puelles L, Porteus MH, Frohman MA, Martin GR, Rubenstein JL. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. J Neurosci. 1993 Jul;13(7):3155–3172. [PubMed]
  • Rubenstein JL, Martinez S, Shimamura K, Puelles L. The embryonic vertebrate forebrain: the prosomeric model. Science. 1994 Oct 28;266(5185):578–580. [PubMed]
  • Price M. Members of the Dlx- and Nkx2-gene families are regionally expressed in the developing forebrain. J Neurobiol. 1993 Oct;24(10):1385–1399. [PubMed]
  • Sharpe PT. Homeobox genes and orofacial development. Connect Tissue Res. 1995;32(1-4):17–25. [PubMed]
  • Horan GS, Ramírez-Solis R, Featherstone MS, Wolgemuth DJ, Bradley A, Behringer RR. Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed. Genes Dev. 1995 Jul 1;9(13):1667–1677. [PubMed]
  • Favier B, Rijli FM, Fromental-Ramain C, Fraulob V, Chambon P, Dollé P. Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton. Development. 1996 Feb;122(2):449–460. [PubMed]
  • Davis AP, Capecchi MR. A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse. Development. 1996 Apr;122(4):1175–1185. [PubMed]
  • Shirasawa T, Sakamoto K, Tkahashi H. Molecular cloning and evolutional analysis of a mammalian homologue of the Distal-less 3 (Dlx-3) homeobox gene. FEBS Lett. 1994 Sep 12;351(3):380–384. [PubMed]
  • Scott MP. Vertebrate homeobox gene nomenclature. Cell. 1992 Nov 13;71(4):551–553. [PubMed]

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