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Vertebrate homeobox genes

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Abstract

In the former part of the review the principal available data aboutHox genes, their molecular organisation and their expression in vertebrate embryos, with particular emphasis for mammals, are briefly summarized.

In the latter part we analysed the expression of four mouse homeobox genes related to twoDrosophila genes expressed in the developing head of the fly: Emx1 and Emx2, related toems, and Otx1 and Otx2, related tootd.

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References

  • Acampora, D., M. D'Esposito, A. Faiella, M. Pannese, E. Migliaccio, F. Morelli, A. Stornaiuolo, V. Nigro, A. Simeone & E. Boncinelli, 1989. The human HOX gene family. Nucleic Acids Res. 17: 10385–10402.

    PubMed  Google Scholar 

  • Akam, M., 1989. Hox and HOM: homologous gene clusters in insects and vertebrates. Cell 57: 347–349.

    PubMed  Google Scholar 

  • Andrews, P. W., 1984. Retinoic acid induces neural differentiation of a cloned human embryonal carcinoma cell linein vitro. Dev. Biol. 103: 285–293.

    PubMed  Google Scholar 

  • Balling, R., G. Mutter, P. Gruss & M. Kessel, 1989. Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox 1.1 in transgenic mice. Cell 58: 337–347.

    PubMed  Google Scholar 

  • Bastian, H. & P. Gruss, 1990. A murine even-skipped homologue. Evx1, is expressed during early embryogenesis and neurogenesis in a biphasic manner. EMBO J. 9: 1839–1852.

    PubMed  Google Scholar 

  • Bieberich, C. J., M. F. Utset, A. Awgulewitsch & F. H. Ruddle, 1990. Evidence for positive and negative regulation of the Hox-3.1 gene. Proc. Natl. Acad. USA 87: 8462–8466.

    Google Scholar 

  • Blumberg, B., C. V. E. Wright, E. M. DeRobertis & K. W. Y. Cho, 1991. Organizer-specific homebox genes inXenopus laevis embryos. Science 253: 194–196.

    PubMed  Google Scholar 

  • Boncinelli, E., A. Simeone, D. Acampora & F. Mavilio, 1991. HOX gene activation by retinoic acid. Trends in Genetics 7: 329–334.

    PubMed  Google Scholar 

  • Brockes, J. P., 1989. Retinoids, homeobox genes and limb morphogenesis. Neuron 2: 1285–1294.

    PubMed  Google Scholar 

  • Chisaka, O. & M. Capecchi, 1991. Regionally restricted developmental defects resulting from targetted disruption of the mouse homeobox gene Hox1.5. Nature 350: 473–479.

    PubMed  Google Scholar 

  • Cho, K. W. Y., J. Goetz, C. V. Wright, A. Fritz, J. Hardwicke & E. M. DeRobertis, 1988. Differential utilization of the same open reading frame in a Xenopus homeobox gene encodes two related proteins sharing the same DNA-binding specificity. EMBO J. 7: 2139–2149.

    PubMed  Google Scholar 

  • Cohen, S. & C. Jurgens, 1991.Drosophila head-lines. Trends Genet. 7: 267–272.

    PubMed  Google Scholar 

  • Dalton, D., R. Chadwick & W. McGinnis, 1989. Expression and embryonic function of empty spiracles: aDrosophila homeobox gene with two patterning functions on the anterior-posterior axis of the embryo. Genes Dev. 3: 1940–1956.

    PubMed  Google Scholar 

  • Dekker, E. J., M. Pannese, E. Houtzager, E. Boncinelli & A. Durston, 1992. Colinearity in theXenopus. 1. Hox-2 complex. Mech. of Dev. 40: 3–12.

    Google Scholar 

  • Dekker, E. J., M. Pannese, E. Houtzager, A. Timmermans, E. Boncinelli & A. Durston, 1992.Xenopus Hox-2 genes are expressed sequentially after the onset of gastrulation and are differentially inducible by retinoic acid. Development, 1992 Supplement: 195–202.

  • De Robertis, E., M. G. Oliver & C. V. E. Wright, 1989. Determination of axial polarity in the vertebrate embryo: homeodomain proteins and homeogenetic induction. Cell 57: 189–191.

    PubMed  Google Scholar 

  • Deschamps, J. & F. Meijlink, 1992. Mammalian homeobox genes in normal development and neoplasia. Critical Reviews in Oncogenesis 3: 117–173.

    PubMed  Google Scholar 

  • D'Esposito, M., F. Morelli, D. Acampora, E. Migliaccio, A. Simeone & E. Boncinelli, 1991. EVX2, a human homeobox gene homologous to the even-skipped segmentation gene, is localized at the 5′ end of HOX4 locus on chromosome 2. Genomics 10: 43–50.

    PubMed  Google Scholar 

  • Dollé, P., J. C. Izpisua-Belmonte, H. Falkenstein, A. Renucci & D. Duboule, 1989. Coordinate expression of the murine Hox-5 complex homeobox containing genes during limb bud pattern formation. Nature 342: 767–772.

    PubMed  Google Scholar 

  • Dollé, P. & D. Duboule, 1989. Two genes members of the murine HOX-5 complex show regional and cell-type specific expression in developing limbs and gonads. EMBO J. 8: 1507.

    PubMed  Google Scholar 

  • Dressler, G. R. & P. Gruss, 1989. Anterior boundaries of the Hox gene expression in mesoderm-derived structures correlate with the linear order along the chromosome. Differentiation 41: 193–201.

    PubMed  Google Scholar 

  • Driever, W. & C. Nüsslein-Volhard, 1988. The bicoid protein determinates position in theDrosophila embryo in a concentration dependent manner. Cell 54: 95–104.

    PubMed  Google Scholar 

  • Duboule, D. & P. Dollé, 1989. The structural and functional organization of the murine Hox gene family resembles that ofDrosophila homeotic genes. EMBO J. 8: 1497–1505.

    PubMed  Google Scholar 

  • Durston, A. J., J. P. M. Timmermans, W. J. Hage, H. F. J. Hendriks, N. J. de Vries, M. Heideveld & P. D. Niewkoop, 1989. Retinoic acid causes an anterior posterior transformation in the developing nervous system. Nature 340: 140–144.

    PubMed  Google Scholar 

  • Faiella, A., M. D'Esposito, M. Rambaldi, D. Acampora, S. Balsofiore, A. Stornauiolo, A. Mallamaci, E. Migliaccio, M. Gulisano, A. Simeone & E. Boncinelli, 1991. Isolation and mapping of EVX1, a human homeobox gene homologous to even-skipped, localized at the 5′ end of HOX1 locus on chromosome 7. Nucleic Acids Res. 19: 6541–6545.

    PubMed  Google Scholar 

  • Figdor, M. & C. Stern, 1993. Segmental organization of embryonic diencephalon. Nature 363: 630–634.

    PubMed  Google Scholar 

  • Frohman, M. A., M. Boyle & G. M. Martin, 1990. Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development 110: 589–607.

    PubMed  Google Scholar 

  • Finkelstein, R. & N. Perrimon, 1991. The molecular genetics of head development inDrosophila melanogaster. Development 112: 899–912.

    PubMed  Google Scholar 

  • Gaunt, S. J., 1987. Homeobox gene Hox-1.5 expression in mouse embryos: earliest detection byin situ hybridisation is during gastrulation. Development 101: 51–60.

    Google Scholar 

  • Gaunt, S. J., 1988. Mouse homeobox gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of Hox-3.1 and Hox-1.5. Development 103: 135–144.

    PubMed  Google Scholar 

  • Gaunt, S. J. & P. B. Singh, 1990. Homeogene expression patterns and chromosomal imprinting. Trends Genet. 6: 208–212.

    PubMed  Google Scholar 

  • Gehring, W. P., 1987. Homeoboxes in the study of development. Science 236: 1245–1252.

    PubMed  Google Scholar 

  • Giampaolo, A., D. Acampora, V. Zappavigna, M. Pannese, M. D'Esposito, A. Carè, A. Faiella, A. Stornaiuolo, G. Russo, A. Simeone, E. Boncinelli & C. Peschle, 1989. Differential expression of human HOX2 genes along the anterior-posterior axis in embryonic central nervous system. Differentiation 40: 191–197.

    PubMed  Google Scholar 

  • Graham, A., N. Papalopulu & R. Krumlauf, 1989. The murine andDrosophila homeobox gene complexes have common features of organization and expression. Cell 57: 367–378.

    PubMed  Google Scholar 

  • Graham, A., M. Maden & R. Krumlauf, 1991. The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development. Development 112: 255–264.

    PubMed  Google Scholar 

  • Holland, P. W. H. & B. L. M. Hogan, 1988. Expression of homeobox genes during mouse development: a review. Genes Dev. 2: 773–782.

    PubMed  Google Scholar 

  • Hunt, P., M. Gulisano, M. Cook, M. H. Sham, A. Faiella, D. Wilkinson, E. Boncinelli & R. Krumlauf, 1991a. A distinct code for the branchial region of the vertebrate head. Nature 353: 861–864.

    PubMed  Google Scholar 

  • Hunt, P., J. Whiting, S. Nonchev, M. H. Sham, H. Marshall, A. Graham, M. Cook, R. Alleman, P. W. J. Rigby, M. Gulisano, A. Faiella, E. Boncinelli & R. Krumlauf, 1991b. The branchial code and its implications for gene regulation, patterning of the nervous system and head evolution. Development, Supplement 2: 63–77.

    Google Scholar 

  • Izpisua-Belmonte, J. C., C. Tickle, P. Dollé, L. Wolpert & D. Duboule, 1991. Expression of homebox Hox-4 genes and the specification of position in chick wing development. Nature 350: 585–589.

    PubMed  Google Scholar 

  • Kessel, M. & P. Gruss, 1990. Murine developmental control genes. Science 249: 374–379.

    PubMed  Google Scholar 

  • Kessel, M. & P. Gruss, 1991. Homeotic transformations of murine prevertebrae and concomitant alteration of Hox codes induced by retinoic acid. Cell 67: 89–104.

    PubMed  Google Scholar 

  • Kuhlenbeck, H., 1973. Morphological Pattern of the Vertebrate Neuroaxis, pp. 471–668 in The Central Nervous System of Vertebrates Edited by S. Karger, Basel.

  • Lawson, K. A., J. J. Meneses & R. A. Pedersen, 1991. Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development 113: 891–911.

    PubMed  Google Scholar 

  • Le Mouellic, H., Y. Lallemand & P. Brulet, 1992. Homeosis in the mouse induced by a null mutation in the Hox-3.1 gene. Cell 69: 251–264.

    PubMed  Google Scholar 

  • Levine, M. & T. Hoey, 1988. Homeobox proteins as sequencespecific transcription factors. Cell 55: 537–540.

    PubMed  Google Scholar 

  • Lewis, E. B., 1978. A gene complex controlling segmentation inDrosophila. Nature 276: 565–570.

    PubMed  Google Scholar 

  • Lufkin, T., A. Dierich, M. LeMeur, M. Mark & P. Chambon, 1991. Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 66: 1105–1119.

    PubMed  Google Scholar 

  • Luskin, M. B., A. L. Pearlman & J. R. Sanes, 1988. Cell lineage in the cerebral cortex of the mouse studiedin vivo andin vitro with a recombinant retrovirus. Neuron 1: 635–647.

    PubMed  Google Scholar 

  • Magli, M. C., P. Barba, A. Celetti, G. De Vita, C. Cillo & E. Boncinelli, 1991. Coordinate regulation of HOX genes in human hematopoietic cells. Proc. Natl. Acad. USA 88: 6348–6352.

    Google Scholar 

  • Martinez, S., M. Wassef & R. M. Alvarado-Mallard, 1991. Induction of a Mesencephalic phenotype in the 2-day-old chick prosencephalon is preceded by the early expression of the homeobox gene en. Neuron 6: 971–981.

    PubMed  Google Scholar 

  • Mavilio, F., A. Simeone, A. Giampaolo, A. Faiella, V. Zappavigna, D. Acampora, G. Poiana, G. Russo, C. Peschle & E. Boncinelli, 1986. Differential and stage-related expression in embryonic tissues of a new human homeobox gene. Nature 324: 664–668.

    PubMed  Google Scholar 

  • McGinnis, W., M. S. Levine, E. Hafen, A. Kuroiwa & W. J. Gehring, 1984. A conserved DNA sequence in homeotic genes of theDrosophila Antennapedia and Bithorax complexes. Nature 308: 428–433.

    PubMed  Google Scholar 

  • McGinnis, W. & R. Krumlauf, 1992. Homeobox genes and axial patterning. Cell 68: 283–302.

    PubMed  Google Scholar 

  • Noden, D., 1988. Interactions and fates of avian craniofacial mesenchyme. Development, 103 Supplement: 121–140.

    Google Scholar 

  • Noji, S., T. Nohno, E. Koyama, K. Muto, K. Ohyama, Y. Aoki, K. Tamura, K. Ohsugi, H. Ide, S. Taniguchi & T. Saito, 1991. Retinoic acid induces polarizing activity but is unlikely to be a morphogen in the chick limb bud. Nature 350: 83–86.

    PubMed  Google Scholar 

  • Oliver, G., C. V. E. Wright, J. Hardwicke & E. M. De Robertis, 1990. Differential antero-posterior expression of two proteins encoded by a homeobox gene inXenopus and mouse embryos. EMBO J. 7: 3199–3209.

    Google Scholar 

  • Puelles, L., J. A. Amat & M. Martinez-de-la-Torre, 1987. Segmentrelated, mosaic neurogenetic pattern in the forebrain and mesencephalon of early chick embryos: I. Topography of AchE-positive neuroblasts up to stage HH18. J. Comp. Neurol. 266: 247–268.

    PubMed  Google Scholar 

  • Puschel, A. W., R. Balling & P. Gruss, 1990. Position-specific activity of the Hox-1.1 promoter in transgenic mice. Development 108: 435–442.

    PubMed  Google Scholar 

  • Sakay, Y., 1987. Neurulation in the mouse. I. The ontogenesis of neural segments and the determination of topographical regions in a central nervous system. Anat. Rec. 218: 450–457.

    PubMed  Google Scholar 

  • Scott, M. P. & A. J. Weiner, 1984. Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax and fushi tarazu loci ofDrosophila. Proc. Natl. Acad. Sci. 81: 4115–4119.

    PubMed  Google Scholar 

  • Scott, M. P., J. W. Tamkun & G. W. Hartzell, 1989. The structure and the function of the homeodomain. Biochim. Biophys. Acta 989: 25–48.

    PubMed  Google Scholar 

  • Scott, M. P., 1992. Vertebrate homeobox gene nomenclature. Cell 71: 551–553.

    PubMed  Google Scholar 

  • Shashikant, C. S., M. F. Utset, S. M. Violette, T. L. Wise, M. Einat, J. W. Pendleton, K. S. Schugart & F. H. Ruddle, 1991. Homeobox genes in mouse development. Crit. Rev. Eukaryotic Gene Expression 1: 207.

    Google Scholar 

  • Simeone, A., M. Pannese, D. Acampora, M. D'Esposito & E. Boncinelli, 1988. At least three human homeoboxes on chromosome 12 belong to the same transcription unit. Nucleic Acids Res. 16: 5379–5390.

    PubMed  Google Scholar 

  • Simeone, A., D. Acampora, L. Arcioni, P. W. Andrews, E. Boncinelli & F. Mavilio, 1990. Sequential activation of HOX3 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346: 763–766.

    Google Scholar 

  • Simeone, A., D. Acampora, V. Nigro, A. Faiella, M. D'Esposito, A. Stornaiuolo, F. Mavilio & E. Boncinelli, 1991. Differential regulation by retinoic acid of the homeobox genes of the four Hox loci in human embryonal carcinoma cells. Mech. of Dev. 33: 215–228.

    Google Scholar 

  • Simeone, A., M. Gulisano, D. Acampora, A. Stornaiuolo, M. Rambaldi & E. Boncinelli, 1992a. Two vertebrate homeobox genes related to theDrosophila empty spiracles gene are expressed in the embryonic cerebral cortex. EMBO J. 11: 2541–2550.

    PubMed  Google Scholar 

  • Simeone, A., D. Acampora, M. Gulisano, A. Stornaiuolo & E. Boncinelli, 1992b. Nested expression domains of four homeobox genes in developing rostral brain. Nature 358: 687–690.

    PubMed  Google Scholar 

  • Simeone, A., D. Acampora, A. Mallamaci, A. Stornaiuolo, M. R. D'Apice, V. Nigro & E. Boncinelli, 1993. A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J. 12: 2735–2747.

    PubMed  Google Scholar 

  • Stornaiuolo, A., D. Acampora, M. Pannese, M. D'Esposito, F. Morelli, E. Migliaccio, M. Rambaldi, A. Faiella, V. Nigro, A. Simeone & E. Boncinelli, 1990. Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci. Cell Differentiation and Development 31: 119–127.

    PubMed  Google Scholar 

  • Stuart, J. J., S. J. Brown, R. B. Beemann & R. E. Denell, 1991. A deficiency of the homeotic complex of the beetleTribolium. Nature 350: 72–74.

    PubMed  Google Scholar 

  • Tam, P. P. L., 1989. Regionalisation of the mouse embryonic ectoderm: allocation of prospective extodermal tissues during gastrulation. Development 107: 55–67.

    PubMed  Google Scholar 

  • Tessier-Lavigne, M., 1992. Axon guidance by molecular gradients. Current Opinion In NeuroBiology 2: 60–65.

    PubMed  Google Scholar 

  • Thaller, C. & G. Eichele, 1987. Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 327: 625–628.

    PubMed  Google Scholar 

  • Tickle, C., B. Alberts, L. Wolpert & J. Lee, 1982. Local application of retinoic acid to the limb bud mimics the action of the polarizing region. Nature 296: 564–566.

    PubMed  Google Scholar 

  • Waneck, N., D. M. Gardiner, K. Muneoka & S. V. Bryant, 1991. Conversion by retinoic acid of anterior cells into ZPA cells in the chick limb bud. Nature 350: 81–83.

    PubMed  Google Scholar 

  • Wieschaus, E., N. Perrimon & R. Finkelstein, 1992. Orthodenticle activity is required for development of medial structures in the larval and adult epidermis ofDrosophila. Development 115: 801–811.

    PubMed  Google Scholar 

  • Wright, C. V. E., K. W. Y. Cho, G. Oliver & E. M. De Robertis, 1989. Vertebrate homeodomain protein: families of region-specific transcription factors. Trends Biochem. Sci. 14: 52–56.

    PubMed  Google Scholar 

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  1. DIBIT, San Raffaele Scientific Institute, via Olgettina 58, 20132, Milano, Italy

    Edoardo Boncinelli, Antonio Mallamaci & Giovanni Lavorgna

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  1. Edoardo Boncinelli
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  2. Antonio Mallamaci
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Boncinelli, E., Mallamaci, A. & Lavorgna, G. Vertebrate homeobox genes. Genetica 94, 127–140 (1994). https://doi.org/10.1007/BF01443427

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