Advertisement
JOURNAL ARTICLES
Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos
A.F. Candia, J. Hu, J. Crosby, P.A. Lalley, D. Noden, J.H. Nadeau, C.V. Wright
Development 1992 116: 1123-1136;

Summary

We have isolated two mouse genes, Mox-1 and Mox-2 that, by sequence, genomic structure and expression pattern, define a novel homeobox gene family probably involved in mesodermal regionalization and somitic differentiation. Mox-1 is genetically linked to the keratin and Hox-2 genes of chromosome 11, while Mox-2 maps to chromosome 12. At primitive streak stages (approximately 7.0 days post coitum), Mox-1 is expressed in mesoderm lying posterior of the future primordial head and heart. It is not expressed in neural tissue, ectoderm, or endoderm. Mox-1 expression may therefore define an extensive ‘posterior’ domain of embryonic mesoderm before, or at the earliest stages of, patterning of the mesoderm and neuroectoderm by the Hox cluster genes. Between 7.5 and 9.5 days post coitum, Mox-1 is expressed in presomitic mesoderm, epithelial and differentiating somites (dermatome, myotome and sclerotome) and in lateral plate mesoderm. In the body of midgestation embryos, Mox-1 signal is restricted to loose undifferentiated mesenchyme. Mox-1 signal is also prominent over the mesenchyme of the heart cushions and truncus arteriosus, which arises from epithelial-mesenchymal transformation and over a limited number of craniofacial foci of neural crest-derived mesenchyme that are associated with muscle attachment sites. The expression profile of Mox-2 is similar to, but different from, that of Mox-1. For example, Mox-2 is apparently not expressed before somites form, is then expressed over the entire epithelial somite, but during somitic differentiation, Mox-2 signal rapidly becomes restricted to sclerotomal derivatives. The expression patterns of these genes suggest regulatory roles for Mox-1 and Mox-2 in the initial anterior-posterior regionalization of vertebrate embryonic mesoderm and, in addition, in somite specification and differentiation.

REFERENCES

    1. Allen J. D.,
    2. Lints T.,
    3. Jenkins N. A.,
    4. Copeland N. G.,
    5. Strasser A.,
    6. Harvey R. P.,
    7. Adams J.
    (1991) Novel murine homeo box gene on chromosome 1 expressed in specific hematopoietic lineages and during embryogenesis. Genes Dev 5, 509–520
    OpenUrlAbstract/FREE Full Text
    1. Anderson R. H.
    (1991) Simplifying the understanding of congenital malformations of the heart. Int. J. Cardiol 32, 131–142
    OpenUrlCrossRefPubMed
    1. Auffray C.,
    2. Rougeon F.
    (1980) Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur. J. Biochem 107, 303–314
    OpenUrlPubMedWeb of Science
    1. Barad M.,
    2. Jack T.,
    3. Chadwick R.,
    4. McGinnis W.
    (1988) A novel, tissue-specific, Drosophila homeobox gene. EMBO J 7, 2151–2161
    OpenUrlPubMed
    1. Bodmer R.,
    2. Jan L. Y.,
    3. Jan Y. N.
    (1990) A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila. Development 110, 661–669
    OpenUrlAbstract/FREE Full Text
    1. Chisaka O.,
    2. Musci T. R.,
    3. Capecchi M. R.
    (1992). Targeted disruption of the mouse homeobox gene hox-1.6 results in developmental defects of the ear, cranial nerves and hindbrain. Nature 355, 516–520
    OpenUrlCrossRefPubMedWeb of Science
    1. Christian J. L.,
    2. Olson D. J.,
    3. Moon R. T.
    (1992) Xwnt-8 modifies the character of mesoderm induced by bFGF in isolated Xenopus ectoderm. EMBO J 111, 33–41
    OpenUrl
    1. Dale L.,
    2. Howes G.,
    3. Price B. M. J.,
    4. Smith J. C.
    (1992) Bonemorphogenetic protein 4: a ventralizing factor in early Xenopus development. Development 115, 573–585
    OpenUrlAbstract
    1. Dohmann C.,
    2. Azpiazu N.,
    3. Frasch M.
    (1990) A new Drosophila homeo box gene is expressed in mesodermal precursor cells of distinct muscles during embryogenesis. Genes Dev 4, 2098–2111
    OpenUrlAbstract/FREE Full Text
    1. Deutsch U.,
    2. Dressler G. R.,
    3. Gruss P.
    (1988) Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development. Cell 53, 617–625
    OpenUrlCrossRefPubMedWeb of Science
    1. Dolle P.,
    2. Izpisua-Belmonte J. C.,
    3. Brown J. M.,
    4. Tickle C.
    (1991) Hox −4 genes and morphogenesis of mammalian genitalia. Genes Dev 5, 1767–1776
    OpenUrlAbstract/FREE Full Text
    1. Duboule D.
    (1992) The vertebrate limb: A model system to study the Hox/Hom gene network during development and evolution. BioEssays 14, 375–384
    OpenUrlCrossRefPubMedWeb of Science
    1. Feinberg A. P.,
    2. Vogelstein B.
    (1983) A technique for labeling DNA restriction endonuclease fragments to high specific activity. Analyt. Biochem 132, 6–13
    OpenUrlCrossRefPubMedWeb of Science
    1. Frohman M. A.,
    2. Boyle M.,
    3. Martin G. R.
    (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
    OpenUrlAbstract/FREE Full Text
    1. Green J. B. A.,
    2. Smith J. C.
    (1991) Growth factors as morphogens: do gradients and thresholds establish body plan?. Trends Genet 7, 245–250
    OpenUrlCrossRefPubMed
    1. Gruss P.,
    2. Walther C.
    (1992) Pax in development. Cell 69, 719–722
    OpenUrlCrossRefPubMedWeb of Science
    1. Guazzi S.,
    2. Price M.,
    3. DeFelice M.,
    4. Damante G.,
    5. Mattei M.-G.,
    6. DiLauro R.
    (1990) Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity. EMBO J 9, 3631–3639
    OpenUrlPubMedWeb of Science
    1. He X.,
    2. Traecy M. N.,
    3. Simmons D. M.,
    4. Ingraham H. A.,
    5. Swanson L. W.,
    6. Rosenfeld M. G.
    (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature 340, 35–42
    OpenUrlCrossRefPubMedWeb of Science
    1. Herrmann B. G.,
    2. Labeit S.,
    3. Poustka A.,
    4. King T. R.,
    5. Lehrach H.
    (1990) Cloning of the T gene required in mesoderm formation in the mouse. Nature 343, 617–622
    OpenUrlCrossRefPubMed
    1. Herrmann B.
    (1991). Expression pattern of the Brachyury gene in whole-mount TWis /TWis mutant embryos.. Development 113, 913–917
    OpenUrlAbstract
    1. Hill R. E.,
    2. Jones P. F.,
    3. Rees A. R.,
    4. Sime C. M.,
    5. Justice M. J.,
    6. Copeland N. G.,
    7. Jenkins N. A.,
    8. Graham E.,
    9. Davidson D. R.
    (1989) A new family of mouse homeobox containing genes: Molecular structure, chromosomal location and developmental expression of Hox 7. Genes Dev 3, 26–37
    OpenUrlAbstract/FREE Full Text
    1. Holland P. W. H.
    (1991) Cloning and evolutionary analysis of msh -like homeobox genes from mouse, zebrafish, and ascidia. Gene 98, 253–257
    OpenUrlCrossRefPubMedWeb of Science
    1. Holland P.
    (1992) Homeobox genes in vertebrate evolution. BioEssays 14, 267–273
    OpenUrlCrossRefPubMedWeb of Science
    1. Izpisua-Belmonte J. C.,
    2. Tickle C.,
    3. Dolle P.,
    4. Wolpert L.,
    5. Duboule D.
    (1991) Expression of the homeobox Hox-4 genes and the specification of position in chick wing development. Nature 350, 585–589
    OpenUrlCrossRefPubMed
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Lapan P. M.,
    4. Wright C. V. E.,
    5. Hogan B. L. M.
    (1992) DVR-4 (Bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction. Development 115, 639–647
    OpenUrlAbstract
    1. Joyner A. L.,
    2. Herrup K.,
    3. Auerbach B. A.,
    4. Davis C. A.,
    5. Rossant J.
    (1991) Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox. Science 251, 1239–1243
    OpenUrlAbstract/FREE Full Text
    1. Kessel M.,
    2. Balling R.,
    3. Gruss P.
    (1990). Variation of cervical vertebrae after expression of a hox-1.1 transgene in mice. Cell 61, 310–308
    OpenUrl
    1. Kessel M.,
    2. Gruss P.
    (1990) Murine developmental control genes. Science 249, 374–379
    OpenUrlAbstract/FREE Full Text
    1. Kimelman D.,
    2. Maas A.
    (1992) Induction of dorsal and ventral mesoderm by ectopically expressed Xenopus basic fibroblast growth factor. Development 114, 261–269
    OpenUrlAbstract
    1. Kozak M.
    (1991) An analysis of vertebrate mRNA sequences: intimations of translational control. J. Cell Biol 115, 887–903
    OpenUrlAbstract/FREE Full Text
    1. Krause H. M.,
    2. Klemenz R.,
    3. Gehring W. J.
    (1988) Expression, modification, and localization of the fushi tarazu protien in Drosophila embryos. Genes Dev 2, 1021–1036
    OpenUrlAbstract/FREE Full Text
    1. Krumlauf R.
    (1992) Evolution of the vertebrate Hox homeobox genes. BioEssays 14, 245–252
    OpenUrlCrossRefPubMedWeb of Science
    1. Krumlauf R.,
    2. McGinnis W.
    (1992) Homeobox genes and axial patterning. Cell 68, 283–302
    OpenUrlCrossRefPubMedWeb of Science
    1. LeMouellic H.,
    2. Lallemand Y.,
    3. Brulet P.
    (1992). Homeosis in the mouse induced by a null mutation in the Hox −1.3 gene. Cell 69, 251–264
    OpenUrlCrossRefPubMedWeb of Science
    1. Li S.,
    2. Crenshaw E. B.,
    3. Rawson E. J.,
    4. Simmons D. M.,
    5. Swanson L. W.,
    6. Rosenfeld M. G.
    (1990) Dwarf locus mutants lacking three pituitary cell types result from mutation in the POU-domain gene pit-1. Nature 347, 528–533
    OpenUrlCrossRefPubMedWeb of Science
    1. Lufkin T.,
    2. Dierich A.,
    3. LeMeur M.,
    4. Mark M.,
    5. Chambon P.
    (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
    OpenUrlCrossRefPubMedWeb of Science
    1. McClearn D.,
    2. Noden D. M.
    (1988) Ontogeny of architectural complexity in embryonic quail visceral arch muscles. Am. J. Anat 183, 277–293
    OpenUrlCrossRefPubMed
    1. Minna J. D.,
    2. Marshall T. H.,
    3. Shaffer-Bermann P. V.
    (1975) Chinese × mouse hybrid cells segregating mouse chromosomes and isozymes. Somat. Cell Genet 1, 355–369
    OpenUrlCrossRefPubMedWeb of Science
    1. Monaghan A. P.,
    2. Davidson D. R.,
    3. Sime C.,
    4. Graham E.,
    5. Baldock R.,
    6. Bhattacharya S. S.,
    7. Hill R. E.
    (1991) The Msh -like homeobox genes define domains in the developing vertebrate eye. Development 112, 1053–1061
    OpenUrlAbstract
    1. Morgan B. A.,
    2. Izpisua-Belmonte J.-C.,
    3. Duboule D.,
    4. Tabin C. J.
    (1992). Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations. Nature 358, 236–239
    OpenUrlCrossRefPubMed
    1. Murphy P.,
    2. Hill R. E.
    (1991). Expression of the mouse labial-like homeobox-containing genes, Hox 2.9 and Hox 1.6, during segmentation of the hindbrain. Development 111, 61–74
    OpenUrlAbstract
    1. Nadeau J. H.,
    2. Berger F. G.,
    3. Cox D. R.,
    4. Crosby J. L.,
    5. Davisson M. T.,
    6. Ferrara D.,
    7. Fuchs E.,
    8. Hart C.,
    9. Hunihan L.,
    10. Lalley P. A.,
    11. Langley S. H.,
    12. Martin G. R.,
    13. Nichols L.,
    14. Phillips S. J.,
    15. Roderick T. R.,
    16. Roop D. R.,
    17. Ruddle F. H.,
    18. Skow L. C.,
    19. Compton J. G.
    (1989) A family of type 1 keratin genes and the homeobox-2 gene complex are closely linked to the rex locus on mouse chromosome 11. Genomics 5, 355–369
    OpenUrlCrossRef
    1. Nadeau J. H.,
    2. Birkenmeier C. S.,
    3. Chowdhury K.,
    4. Crosby J. L.,
    5. Lalley P. A.
    (1990) Zinc finger protein gene complexes on mouse chromosomes 8 and 11. Genomics 8, 469–476
    OpenUrlCrossRefPubMed
    1. Nadeau J. H.,
    2. Herrmann B.,
    3. Bucan M.,
    4. Berkart D.,
    5. Crosby J. L.,
    6. Erhart M. A.,
    7. Kosowsky M.,
    8. Kraus J. P.,
    9. Michiels F.,
    10. Schnattinger A.,
    11. Tchethen M.-B.,
    12. Varnum D.,
    13. Willison K.,
    14. Lehrach H.,
    15. Barlow D.
    (1991) Genetic maps of mouse chromosome 17 including 12 new anonymous DNA loci and 25 anchor loci. Genomics 9, 78–89
    OpenUrlCrossRefPubMed
    1. Noden D. M.
    (1991) Origins and patterning of avian outflow tract endocardium. Development 111, 867–876
    OpenUrlAbstract/FREE Full Text
    1. Nohno T.,
    2. Noji S.,
    3. Koyama E.,
    4. Ohyama K.,
    5. Myokai F.,
    6. Kuroiwa A.,
    7. Saito T.,
    8. Taniguchi S.
    (1991) Involvement of the Chox-4 chicken homeobox genes in determination of anteroposterior axial polarity during limb development. Cell 64, 1197–1205
    OpenUrlCrossRefPubMedWeb of Science
    1. Opstelten D.-J. E.,
    2. Vogels R.,
    3. Robert B.,
    4. Kalkhoven E.,
    5. Zwartkruis F.,
    6. deLaaf L.,
    7. Destree O. H.,
    8. Deschamps J.,
    9. Lawson K. A.,
    10. Meijlink F.
    (1991) The mouse homeobox gene, S8, is expressed during embryogenesis predominantly in mesenchyme. Mech. Dev 34, 29–42
    OpenUrlCrossRefPubMedWeb of Science
    1. Orr-Urtreger A.,
    2. Bedford M. T.,
    3. Do M. S.,
    4. Eisenbach L.,
    5. Lonai P.
    (1992) Developmental expression of the alpha receptor for platelet-derived growth factor, which is deleted in the embryonic lethal Patch mutation. Development 115, 289–303
    OpenUrlAbstract
    1. Pelton R. W.,
    2. Nomura S.,
    3. Moses H. L.,
    4. Hogan B. L. M.
    (1989) Expression of transforming growth factor 2 RNA during murine embryogenesis. Development 106, 759–767
    OpenUrlAbstract/FREE Full Text
    1. Popp R. A.,
    2. Lalley P. A.,
    3. Whitney J. B.,
    4. Anderson W. F.
    (1981) Mouse alpha-globin genes and alpha-globin-like pseudogenes are not syntenic. Proc. Natl. Acad. Sci. USA 78, 6362–6366
    OpenUrlAbstract/FREE Full Text
    1. Rashbass P.,
    2. Cooke L.A.,
    3. Herrmann B. G.,
    4. Beddington R. S. P.
    (1991) A cell autonomous function of brachyury in T/T embryonic stem cell chimaeras. Nature 353, 348–351
    OpenUrlCrossRefPubMedWeb of Science
    1. Rosenfeld M. G.
    (1991) POU-domain transcription factors- pou-er-ful developmental regulators. Genes Dev 5, 897–907
    OpenUrlFREE Full Text
    1. Sassoon D.,
    2. Lyons G.,
    3. Wright W. E.,
    4. Lin V.,
    5. Lassar A.,
    6. Weintraub H.,
    7. Buckingham M.
    (1989) Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature 341, 303–307
    OpenUrlCrossRefPubMed
    1. Schatteman G. C.,
    2. Morrisongraham K.,
    3. Vankoppen A.,
    4. Weston J. A.,
    5. Bowen-Pope D. F.
    (1992) Regulation and role of PDGF receptor alpha-subunit expression during embryogenesis. Development 115, 123–131
    OpenUrlAbstract
    1. Scott M. A.,
    2. Tamkun J. W.,
    3. Hartzell G. W.
    (1989) The structure and function of the homeodomain. Biochim. Biophys. Acta 989, 25–48
    OpenUrlPubMedWeb of Science
    1. Silver J.,
    2. Buckler C. E.
    (1986) Statistical considerations for linkage analysis using recombinant inbred strains and backcrosses. Proc. Nat. Acad. Sci. USA 83, 1423–1427
    OpenUrlAbstract/FREE Full Text
    1. Smith W. C.,
    2. Harland R. M.
    (1991) Injected Xwnt-8 acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center. Cell 67, 753–765
    OpenUrlCrossRefPubMedWeb of Science
    1. Sokol S.,
    2. Christian J. L.,
    3. Moon R. T.,
    4. Melton D. A.
    (1991) Injected wnt RNA induces a complete body axis in Xenopus embryos. Cell 67, 741–752
    OpenUrlCrossRefPubMedWeb of Science
    1. Sundin O. H.,
    2. Busse H. G.,
    3. Rogers M. B.,
    4. Gudas L. J.,
    5. Eichele G.
    (1990). Region-specific expression in early chick and mouse embryos of Ghox-lab and Hox 1.6, vertebrate homeobox-containing genes related to Drosophilalabial. Development 108, 47–58
    OpenUrlAbstract
    1. Wilkinson D. G.,
    2. Bhatt S.,
    3. Herrmann B. G.
    (1990) Expression pattern of the mouse T gene and its role in mesoderm formation. Nature 343, 657–659
    OpenUrlCrossRefPubMedWeb of Science
    1. Wright C. V. E.,
    2. Cho K. W. Y.,
    3. Burglin T. R.,
    4. DeRobertis E. M.
    (1987) A Xenopus laevis gene encodes both homeobox-containing and homeobox-less transcripts. EMBO J 6, 4083–4094
    OpenUrlPubMedWeb of Science
    1. Wright C. V. E.,
    2. Schnegelsberg P.,
    3. DeRobertis E. M.
    (1988) XlHbox8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. Development 104, 787–794
    OpenUrl
    1. Wright C. V. E.,
    2. Cho K. W. Y.,
    3. Hardwicke J.,
    4. Collins R. H.,
    5. DeRobertis E. M.
    (1989) Interference with function of a homeobox gene in Xenopus embryos produces malformations of the anterior spinal cord. Cell 59, 81–93
    OpenUrlCrossRefPubMedWeb of Science
    1. Wright C. V. E.
    (1991) Vertebrate homeobox genes. Current Op. Cell Biol 3, 976–982
    OpenUrlCrossRefPubMed
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos
A.F. Candia, J. Hu, J. Crosby, P.A. Lalley, D. Noden, J.H. Nadeau, C.V. Wright
Development 1992 116: 1123-1136;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.

Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.

Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights