Development Genes and Evolution

, Volume 217, Issue 4, pp 263–273 | Cite as

Duplicated Abd-B class genes in medaka hoxAa and hoxAb clusters exhibit differential expression patterns in pectoral fin buds

  • Naofumi Takamatsu
  • Gene Kurosawa
  • Masayoshi Takahashi
  • Ryouichi Inokuma
  • Minoru Tanaka
  • Akira Kanamori
  • Hiroshi Hori
Original Article


Hox genes form clusters. Invertebrates and Amphioxus have only one hox cluster, but in vertebrates, they are multiple, i.e., four in the basal teleost fish Polyodon and tetrapods (HoxA, B, C, D), but seven or eight in common teleosts. We earlier completely sequenced the entire hox gene loci in medaka fish, showing a total of 46 hox genes to be encoded in seven clusters (hoxAa, Ab, Ba, Bb, Ca, Da, Db). Among them, hoxAa, hoxAb and hoxDa clusters are presumed to be important for fin-to-limb evolution because of their key role in forelimb and pectoral fin development. In the present study, we compared genome organization and nucleotide sequences of the hoxAa and hoxAb clusters to these of tetrapod HoxA clusters, and found greater similarity in hoxAa case. We then analyzed expression of Abd-B family genes in the clusters. In the trunk, those from the hoxAa cluster, i.e., hoxA9a, hoxA10a, hoxA11a and hoxA13a, were expressed in a manner keeping the colinearity rule of the hox expression as those of tetrapods, while those from the hoxAb cluster, i.e., hoxA9b, hoxA10b, hoxA11b and hoxA13b, were not. In the pectoral fins, the hoxAa cluster was expressed in split domains and did not obey the rule. By contrast, those from the hoxAb and hoxDa clusters were expressed in a manner keeping the rule, i.e., an ancestral pattern similar to those of tetrapods. It is plausible that this differential expression of the two clusters is caused by changes occurred in global control regions after cluster duplications.


Oryzias latipes Pectoral fin bud Hox Abd-B family Colinearity Subfunctionalization 


  1. Akimenko MA, Ekker M (1995) Anterior duplication of the Sonic hedgehog expression pattern in the pectoral fin buds of zebrafish treated with retinoic acid. Dev Biol 170:243–247PubMedCrossRefGoogle Scholar
  2. Amores A, Force A, Yan YL, Joly L, Amemiya C, Fritz A, Ho RK, Langeland J, Prince V, Wang YL, Westerfield M, Ekker M, Postlethwait JH (1998) Zebrafish hox clusters and vertebrate genome evolution. Science 282:1711–1714PubMedCrossRefGoogle Scholar
  3. Amores A, Suzuki T, Yan YL, Pomeroy J, Singer A, Amemiya C, Postlethwait JH (2004) Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin fish. Genome Res 14:1–10PubMedCrossRefGoogle Scholar
  4. Anand S, Wang WC, Powell DR, Bolanowski SA, Zhang J, Ledje C, Pawashe AB, Amemiya CT, Shashikant CS (2003) Divergence of Hoxc8 early enhancer parallels diverged axial morphologies between mammals and fishes. Proc Natl Acad Sci USA 100:15666–15669PubMedCrossRefGoogle Scholar
  5. Belting HG, Shashikant CS, Ruddle FH (1998) Modification of expression and cis-regulation of Hoxc8 in the evolution of diverged axial morphology. Proc Natl Acad Sci USA 95:2355–2360PubMedCrossRefGoogle Scholar
  6. Bruce AE, Oates AC, Prince VE, Ho RK (2001) Additional hox clusters in the zebrafish: divergent expression patterns belie equivalent activities of duplicate hoxB5 genes. Evol Dev 3:127–144PubMedCrossRefGoogle Scholar
  7. Burke AC, Nelson CE, Morgan BA, Tabin C (1995) Hox genes and the evolution of vertebrate axial morphology. Development 121:333–346PubMedGoogle Scholar
  8. Charité J, McFadden DG, Olson EN (2000) The bHLH transcription factor dHAND controls Sonic hedgehog expression and establishment of the zone of polarizing activity during limb development. Development 127:2461–2470PubMedGoogle Scholar
  9. Dietrich S, Abou-Rebyeh F, Brohmann H, Bladt F, Sonnenberg-Riethmacher E, Yamaai T, Lumsden A, Brand-Saberi B, Birchmeier C (1999) The role of SF/HGF and c-Met in the development of skeletal muscle. Development 126:1621–1629PubMedGoogle Scholar
  10. Dollé P, Izpisúa-Belmonte JC, Falkenstein H, Renucci A, Duboule D (1989) Coordinate expression of the murine Hox-5 complex homeobox-containing genes during limb pattern formation. Nature 342:767–772PubMedCrossRefGoogle Scholar
  11. Duboule D, Dollé P (1989) The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J 8:1497–1505PubMedGoogle Scholar
  12. Ferrier DE, Minguillón C, Holland PW, Garcia-Fernàndez J (2000) The amphioxus Hox cluster: deuterostome posterior flexibility and Hox14. Evol Dev 2:284–293PubMedCrossRefGoogle Scholar
  13. Gehring WJ, Affolter M, Bürglin T (1994) Homeodomain proteins. Annu Rev Biochem 63:487–526PubMedCrossRefGoogle Scholar
  14. Gérard M, Duboule D, Zákány J (1993) Structure and activity of regulatory elements involved in the activation of the Hoxd-11 gene during late gastrulation. EMBO J 12:3539–3550PubMedGoogle Scholar
  15. Haines L, Neyt C, Gautier P, Keenan DG, Bryson-Richardson RJ, Hollway GE, Cole NJ, Currie PD (2004) Met and Hgf signaling controls hypaxial muscle and lateral line development in the zebrafish. Development 131:4857–4869PubMedCrossRefGoogle Scholar
  16. Harding K, McGinnis W, Wedeen C, Levine M (1985) Spatially regulated expression of homeotic genes in Drosophila. Science 229:1236–1242PubMedCrossRefGoogle Scholar
  17. Hart CP, Fainsod A, Ruddle FH (1987) Sequence analysis of the murine Hox-2.2, -2.3 and -2.4 homeo boxes: evolutionary and structural comparisons. Genomics 1:182–195PubMedCrossRefGoogle Scholar
  18. Holland PW (1999) Gene duplication: past, present and future. Semin Cell Dev Biol 10:541–547PubMedCrossRefGoogle Scholar
  19. Holland PW, Garcia-Fernàndez J (1996) Hox genes and chordate evolution. Dev Biol 173:382–395PubMedCrossRefGoogle Scholar
  20. Inohaya K, Yasumasu S, Ishimaru M, Ohyama A, Iuchi I, Yamagami K (1995) Temporal and spatial patterns of gene expression for the hatching enzyme in the teleost embryo, Oryzias latipes. Dev Biol 171:374–385PubMedCrossRefGoogle Scholar
  21. Inohaya K, Yasumasu S, Yasumasu I, Iuchi I, Yamagami K (1999) Analysis of the origin and development of hatching gland cells by transplantation of the embryonic shield in the fish, Oryzias latipes. Dev Growth Differ 41:557–566PubMedCrossRefGoogle Scholar
  22. Iwamatsu T (2004) Stages of normal development in the medaka Oryzias latipes. Mech Dev 121:605–618PubMedCrossRefGoogle Scholar
  23. Izpisúa-Belmonte JC, Falkenstein H, Dollé P, Renucci A, Duboule D (1991) Murine genes related to the Drosophila Abd-B homeotic genes are sequentially expressed during development of the posterior part of the body. EMBO J 10:2279–2289PubMedGoogle Scholar
  24. Kessel M, Gruss P (1990) Murine development control genes. Science 249:374–379PubMedCrossRefGoogle Scholar
  25. Krumlauf R (1992) Evolution of the vertebrate Hox homeobox genes. Bioessays 14:245–252PubMedCrossRefGoogle Scholar
  26. Kurosawa G, Yamada K, Ishiguro H, Hori H (1999) Hox gene complexity in medaka fish may be similar to that in pufferfish rather than zebrafish. Biochem Biophys Res Commun 260:66–70PubMedCrossRefGoogle Scholar
  27. Kurosawa G, Takamatsu N, Takahashi M, Sumitomo M, Sanaka M, Yamada K, Nishii K, Matsuda M, Asakawa S, Ishiguro H, Miura K, Kurosawa Y, Shimizu N, Kohara Y, Hori H (2006) Organization and structure of hox gene loci in medaka genome and comparison with those of pufferfish and zebrafish genomes. Gene 370:75–82PubMedCrossRefGoogle Scholar
  28. Levine M, Hafen E, Garber RL, Gehring WJ (1983) Spatial distribution of Antennapedia transcripts during Drosophila development. EMBO J 2:2037–2046PubMedGoogle Scholar
  29. Metscher BD, Takahashi K, Crow K, Amemiya C, Nonaka DF, Wagner DP (2005) Expression of Hoxa-11 and Hoxa-13 in the pectoral fin of a basal ray-finned fish, Polyodon spathula: implications for the origin of tetrapod limbs. Evol Dev 7:186–195PubMedCrossRefGoogle Scholar
  30. Naruse K, Fukamachi S, Mitani H, Kondo M, Matsuoka T, Kondo S, Hanamura N, Morita Y, Hasegawa K, Nishigaki R, Shimada A, Wada H, Kusakabe T, Suzuki N, Kinoshita M, Kanamori A, Terado T, Kimura H, Nonaka M, Shima A (2000) A detailed linkage map of medaka, Oryzias latipes: comparative genomics and genome evolution. Genetics 154:1773–1784PubMedGoogle Scholar
  31. Neumann CJ, Grandel H, Gaffield W, Schulte-Merker F, Nüsslein-Volhard C (1999) Transient establishment of anterior–posterior polarity in the zebrafish pectoral fin bud in the absence of sonic hedgehog activity. Development 126:4817–4826PubMedGoogle Scholar
  32. Neyt C, Jagla K, Thisse C, Thisse B, Haines L, Currie PD (2000) Evolutionary origins of vertebrate appendicular muscle. Nature 408:82–86PubMedCrossRefGoogle Scholar
  33. Prince VE, Joly L, Ekker M, Ho RK (1998) Zebrafish hox genes: genomic organization and modified collinear expression patterns in the trunk. Development 125:407–420PubMedGoogle Scholar
  34. Riddle RD, Johnson RL, Laufer E, Tabin C (1993) Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75:1401–1416PubMedCrossRefGoogle Scholar
  35. Santini S, Boore JL, Meyer A (2003) Evolutionary conservation of regulatory elements in vertebrate Hox gene clusters. Genome Res 13:1111–1122PubMedCrossRefGoogle Scholar
  36. Schwartz S, Zhang Z, Frazer KA, Smit A, Riemer C, Bouck J, Gibbs R, Hardison R, Miller W (2000) PipMaker—a web server for aligning two genomic DNA sequences. Genome Res 10:577–586PubMedCrossRefGoogle Scholar
  37. Scott MP (1992) Vertebrate homeobox gene nomenclature. Cell 71:551–553PubMedCrossRefGoogle Scholar
  38. Sordino P, van der Hoeven F, Duboule D (1995) Hox gene expression in teleost fins and the origin of vertebrate digits. Nature 375:678–681PubMedCrossRefGoogle Scholar
  39. Sordino P, Duboule D, Kondo T (1996) Zebrafish Hoxa and Evx-2 genes: cloning, developmental expression and implication for the functional evolution of posterior Hox genes. Mech Dev 59:165–175PubMedCrossRefGoogle Scholar
  40. Spitz F, Gonzalez F, Duboule D (2003) A global control region defines a chromosomal regulatory landscape containing the HoxD cluster. Cell 113:405–417PubMedCrossRefGoogle Scholar
  41. Tümpel S, Cambronero F, Widedemann LM, Krumlauf R (2006) Evolution of cis element in the differential expression of two Hoxa2 coparalogous genes in pufferfish (Takifugu rubripes). Proc Natl Acad Sci USA 103:5419–5424PubMedCrossRefGoogle Scholar
  42. van der Hoeven F, Sordino P, Fraudeau N (1996a) Teleost HoxD and HoxA genes: comparison with tetrapods and functional evolution of the HOXD complex. Mech Dev 54:9–21PubMedCrossRefGoogle Scholar
  43. van der Hoeven F, Zákány J, Duboule D (1996b) Gene transpositions in the HoxD complex reveal a hierarchy of regulatory controls. Cell 85:1025–1035PubMedCrossRefGoogle Scholar
  44. Yamomoto M, Gotoh Y, Tamura K, Tanaka M, Kawakami A, Ide H, Kuroiwa A (1998) Coordinated expression of Hoxa-11 and Hoxa-13 during limb muscle patterning. Development 125:1325–1335Google Scholar
  45. Yokouchi Y, Sasaki H, Kuroiwa A (1991) Homeobox gene expression correlated with the bifurcation process of limb cartilage development. Nature 353:443–445PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Naofumi Takamatsu
    • 1
  • Gene Kurosawa
    • 1
    • 2
  • Masayoshi Takahashi
    • 1
  • Ryouichi Inokuma
    • 1
  • Minoru Tanaka
    • 3
  • Akira Kanamori
    • 1
  • Hiroshi Hori
    • 1
  1. 1.Division of Biological Science, Graduate School of ScienceNagoya UniversityNagoyaJapan
  2. 2.Institute for Comprehensive Medical ScienceFujita Health UniversityToyoakeJapan
  3. 3.Laboratory of Molecular Genetics for ReproductionNational Institute for Basic BiologyOkazakiJapan

Personalised recommendations