Murine Homeo-Genes: Some Aspects of their Organisation and Structure

  • Denis Duboule
  • Brigitte Galliot
  • Agnès Baron
  • Mark S. Featherstone
Conference paper
Part of the NATO ASI Series book series (volume 26)

Abstract

The mammalian genome contains at least 30 sequences related to the Drosophila Antennapedia (Antp) homeo-box (see references below). Most, if not all, of these sequences are present in the coding regions of actively transcribed genes (1–23) and thus define a homeo-gene family of as yet unknown function. It is supposed, by analogy with similar genes in insects (24, 25 and refs. therein), and by structural comparisons with prokaryotic DNA-binding domains (26), that such homeo-genes are involved in a regulatory network during ontogenesis through a DNA-binding activity. This gene family might therefore be of considerable importance in vertebrate morphogenesis, pattern formation and the specification of cell lineages. In this paper, we present some aspects of the structure of the homeo-gene family and homeo-genes themselves. Organisational features apparent at both levels may provide insight into their evolution, phylogenetic relationships, and possible modes of action. These aspects will be considered separately and exemplified by the situation as it is known in the house mouse.

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References

  1. 1.
    Colberg-Poley, A.M., Voss, S.D., Chowdhury, K. and Gruss, P. (1985a) Structural analysis of murine genes containing homeo-box sequences and their expression in embryonal carcinoma cells. Nature 314: 713–716.PubMedCrossRefGoogle Scholar
  2. 2.
    Col berg-Poley, A.M., Voss, S.D., Chowdhury, K., Stewart, C.L., Wagner, E.F. and Gruss, P. (1985b) Clustered homeo-boxes are differentially expressed during murine development. Cell 43: 39–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Odenwald, W., Taylor, C., Palmer-Hill, F., Tani, M. and Lazzarini, R. (1987b) Expression of the murine Mox6–3 homeo-box protein is regulated by cell-cell contact. ICSU Short Repts. 7: 126.Google Scholar
  4. 4.
    Duboule, D., Baron, A., Mähl, P. and Galliot, B. (1986) A new homeo-box is present in overlapping cosmid clones which define the mouse Hox-1 locus. EMBO J. 5: 1973–1980.PubMedGoogle Scholar
  5. 5.
    Wolgemuth, D.J., Engelmyer, E., Duggal, R.N., Gizang-Ginsberg, E., Mutter, G.L., Ponzetto, C., Viviano, C. and Zakeri, Z.F. (1986) Isolation of a mouse cDNA coding for a developmentally regulates testis-specific transcript containing homeo-box homology. EMBO J. 5: 1229–1235.PubMedGoogle Scholar
  6. 6.
    Rubin, M.R., Toth, L.E., Patel, M.D., d’Eustachio, P. and Chi Nguyen-Huu, M. (1986) A mouse homeo-box gene is expressed in spermatocytes and embryos. Science 233, 663–667.PubMedCrossRefGoogle Scholar
  7. 7.
    McGinnis, W., Hart, C.P., Gehring, W.J. and Ruddle, F.H. (1984b) Molecular cloning and chromosome mapping of a mouse DNA sequence homologous to homeotic genes of Drosophila. Cell 38: 675–680.PubMedCrossRefGoogle Scholar
  8. 8.
    Gaunt, S.J. (1987) Homeo-box gene Hox-1.5 expression in mouse embryos: earliest detected by in situ hybridization is during gastrulation. Development 101: 51–60.PubMedGoogle Scholar
  9. 9.
    Fainsod, A., Awgulewitsch, A. and Ruddle, F.H. (1987) Expression of the murine homeo-box gene Hox-1.5 during embryogenesis. Developmental Biology 124: 125–133.PubMedCrossRefGoogle Scholar
  10. 10.
    Baron, A., Featherstone, M.S., Hill, R.E., Hall, A., Galliot, B. and Duboule, D. (1987) Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex. EMBO J. 6: 2977–2986.PubMedGoogle Scholar
  11. 11.
    Rubin, M.R., Toth, L.E., Patel, M.D., d’Eustachio, P. and Chi Nguyen-Huu, M. (1986) A mouse homeo-box gene is expressed in spermatocytes and embryos. Science 233: 663–667.PubMedCrossRefGoogle Scholar
  12. 12.
    Jackson, I.J., Schofield, P. and Hogan, B. (1985) A mouse homeo-box gene is expressed during embryogenesis and in adult kidney. Nature 317: 745–748.PubMedCrossRefGoogle Scholar
  13. 13.
    Krumlauf, R., Holland, P.W.H., McVey, J.H. and Hogan, B.L.M. (1987) Developmental and spatial patterns of expression of the mouse homeo-box gene, Hox-2.1. Development 99: 603–617.PubMedGoogle Scholar
  14. 14.
    Hart, C.P., Awgulewitsch, A., Fainsod, A., McGinnis, W. and Ruddle, F.H. (1985) Homeo-box gene complex on mouse chromosome 11: molecular cloning expression in embryogenesis, and homology to a human homeo-box locus. Cell 43: 9–18.PubMedCrossRefGoogle Scholar
  15. 15.
    Meijlink, F., de Laaf, R., Verrijzer, P., Destrée, O., Kroezen, V. and Deschamps, J. (1987) A mouse homeo-box containing gene on chromosome 11: sequence and tissue-specific expression. Nucl. Acids Res. 17: 6773–6786.CrossRefGoogle Scholar
  16. 16.
    Deschamps, J., de Laaf, R., Joosen, L., Meijlink, F. and Destrée, O. (1987a) Abundant expression of homeo-box genes in mouse embryonal carcinoma cells correlates with chemically induced differentiation. Proc. Natl. Acad. Sci. USA 84: 1304–1308.PubMedCrossRefGoogle Scholar
  17. 17.
    Lonai, P., Arman, E., Czosnek, H., Ruddle, F.H. and Blatt, C. New murine homeo-boxes; structure, chromosomal assignment and differential expression in the embryo and in adult erythropoiesis. Gene, in press.Google Scholar
  18. 18.
    Awgulewitsch, A., Utset, M.F., Hart, C.P., McGinnis, W. and Ruddle, F.H. (1986) Spatial restriction in expression of a mouse homeo-box locus within the central nervous system. Nature 320: 328–335.PubMedCrossRefGoogle Scholar
  19. 19.
    Breier, G., Bucan, M., Francke, U., Colberg-Poley, A.M. and Gruss, P. (1986) Sequential expression of murine homeo-box genes during F9 EC cell differentiation. EMBO J. 5: 2209–2217.PubMedGoogle Scholar
  20. 20.
    Le Mouellic, H., Condamine, H. and Brûlet, P. Pattern of transcription of the homeo-gene Hox-3.1 in the mouse embryo, in press.Google Scholar
  21. 21.
    Featherstone, M.S., Baron, A., Gaunt, S.J., Mattei, M.G. and Duboule, D. (1988) Hox-5.1 defines a homeo-gene-locus on mouse chromosome 2, submitted for publication.Google Scholar
  22. 22.
    Sharpe, P.T., Miller, J.R., Evans, E.P., Burtenshaw, M.D. and Gaunt, S.J. Hox 6: a mouse homeo-box gene locus on chromosome 14, in press.Google Scholar
  23. 23.
    Dony, C. and Gruss, P. (1987) Specific expression of the Hox-1.3 homeo-box gene in murine embryonic structures originating from or induced by the mesoderm. EMBO J. 6: 2965–2975.PubMedGoogle Scholar
  24. 24.
    Gehring, W.J. (1985) The homeo-box: A key to the understanding of development ? Cell 40: 3–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Gehring, W.J. (1987) Homeo-boxes in the study of development. Science 236: 1245–1252.PubMedCrossRefGoogle Scholar
  26. 26.
    Laughon, A. and Scott, M.P. (1984) Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature 310: 25–31.PubMedCrossRefGoogle Scholar
  27. 27.
    Martin, G.R., Boncinelli, E., Duboule, D., Gruss, P., Jackson, I., Krumlauf, R., Lonai, P., McGinnis, W., Ruddle, F. and Wolgemuth, D. (1987) Nomenclature for homeo-box-containing genes. Nature 325: 21–22.PubMedCrossRefGoogle Scholar
  28. 28.
    Bucan, M., Yang-Feng, T., Colberg-Poley, A.M., Wolgemuth, D.J., Guenet, J.L., Francke, U. and Lehrach, H. (1986) Genetic and cytogenetic localisation of the homeo-box containing genes on mouse chromosome 6 and human chromosome 7. EMBO J. 5: 2899–2905.PubMedGoogle Scholar
  29. 29.
    Rabin, M., Hart, C.P., Ferguson-Smith, A., McGinnis, W., Levine, M. and Ruddle, F.H. (1985) Two homeo-box loci mapped in evolutionarily related mouse and human chromosomes. Nature 314: 175–178.PubMedCrossRefGoogle Scholar
  30. 30.
    Mavilio, F., Simeone, A., Boncinelli, E. and Andrews, P.W. Activation of four homeo-box gene clusters in human embryonal carcinoma cells induced to differentiate by retinoic acid, in press.Google Scholar
  31. 31.
    Harvey, R.P., Tabin, C.J. and Melton, D.A. (1986) Embryonic expression and nuclear localization of Xenopus homeo-box gene products. EMBO J. 5: 1237–1244.PubMedGoogle Scholar
  32. 32.
    Regulski, M., Harding, K., Kostriken, R., Karch, F., Levine, N. and McGinnis, W. (1985) Homeo-box genes of the Antennapedia and Bithorax complexes of Drosophila. Cell 43: 71–80.PubMedCrossRefGoogle Scholar
  33. 33.
    McGinnis, W., Garber, R.L., Wirz, J., Kuroiwa, A. and Gehring, W.J. (1984a) A homologous protein coding sequence in Drosophila homeotic genes and its conservation in other metazoans. Cell 38: 403–409.CrossRefGoogle Scholar
  34. 34.
    Hart, C.P., Fainsod, A. and Ruddle, F.H. (1987) Sequence analysis of the murine Hox-2.2, Hox-2.3 and Hox-2.4 homeo-boxes: evolutionary and structural comparisons. Genomics 1: 182–195.PubMedCrossRefGoogle Scholar
  35. 35.
    Regulski, M., McGinnis, N., Chadwick, R. and McGinnis, W. (1987) Developmental and molecular analysis of Deformed: a homeotic gene controlling Drosophila head development. EMBO J. 6: 767–777.PubMedGoogle Scholar
  36. 36.
    Hoey, T., Doyle, H.J., Harding, K., Wedeen, C. and Levine, M. (1986) Homeo-box gene expression in anterior and posterior regions of the Drosophila embryo. Proc. Natl. Acad. Sci. USA 83: 4809–4813.PubMedCrossRefGoogle Scholar
  37. 37.
    Mavilio, F., Simeone, A., Giampaolo, A., Faiella, A., Zappavigna, V., Acampora, D., Poiana, G., Russo, G., Peschle, C. and Boncinelli, E. (1986) Differential and stage-related expression in embryonic tissues of a new human homeo-box gene. Nature 324: 664–668.PubMedCrossRefGoogle Scholar
  38. 38.
    Beachy, P.A., Helfand, S.L. and Hogness, D.S. (1985) Segmental distribution of Bithorax complex proteins during Drosophila melanogaster development. Nature 313: 545–551.PubMedCrossRefGoogle Scholar
  39. 39.
    Weinzierl, R., Axton, J.M., Ghysen, A. and Akam, M. (1987) Genes and Development 1: 386–397.CrossRefGoogle Scholar
  40. 40.
    Kessel, M., Schulze, F., Fibi, M. and Gruss, P. (1987) Primary structure and nuclear localization of a murine homeo-domain protein. Proc. Natl. Acad. Sci. USA 84: 5306–5310.PubMedCrossRefGoogle Scholar
  41. 41.
    Mlodzik, M., Fjose, A. and Gehring, W.J. (1985) Isolation of caudal, a Drosophila homeo-box-containing gene with maternal expression, whose transcripts form a concentration gradient at the preblastoderm stage. EMBO J. 4: 2961–2969.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Denis Duboule
    • 1
  • Brigitte Galliot
    • 1
  • Agnès Baron
    • 1
  • Mark S. Featherstone
    • 1
  1. 1.Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l’InsermFaculté de MédecineStrasbourg CédexFrance

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