Advertisement
JOURNAL ARTICLES
Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells
C. Kimura, N. Takeda, M. Suzuki, M. Oshimura, S. Aizawa, I. Matsuo
Development 1997 124: 3929-3941;

Summary

Previous studies suggested that the Otx2 gene plays an essential role in the development of cranial skeletons and nerves of mesencephalic neural crest origin. To clarify this role, we have identified the cis-acting elements in mouse and pufferfish Otx2 genes responsible for the expression in the crest cells using a transgenic approach with the lacZ reporter gene. In mouse, 49 bp sequences in the proximal 5′ region upstream were essential and sufficient to direct the transgene expression in the cephalic mesenchyme. In pufferfish, the 1.1 kb distal region, located far downstream (from +14.4 to +15.5 kb), had almost identical activity. Between them, several DNA sequences were conserved, and mutational analyses indicated that motif A was critical for the transgene expression in the premandibular region while motif B was critical in both premandibular and mandibular regions. Motif B, CTAATTA, contains the core motif for binding of homeodomain proteins while motif A, TAAATCTG, does not match any known consensus binding sequences for transcriptional factors. The cephalic mesenchyme that expressed beta-galactosidase under these cis-elements is most likely to correspond to mesencephalic crest cells. Thus the molecular machinery regulating Otx2 expression in these cells appears to be conserved between mouse and fish, implying a crucial role of the Otx2 gene in development of the neural-crest-derived structures of the gnathostome rostral head.

REFERENCES

    1. Acampora D.,
    2. Mazan S.,
    3. Lallemand Y.,
    4. Avantaggiato V.,
    5. Maury M.,
    6. Simeone A.,
    7. Brûlet P.
    (1995) Forebrain and midbrain regions are deleted in Otx2/ mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121, 3279–3290
    OpenUrlAbstract
    1. Ang S.-L.,
    2. Conlon R. A.,
    3. Jin O.,
    4. Rossant J.
    (1994) Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants. Development 120, 2979–2989
    OpenUrlAbstract
    1. Ang S.-L.,
    2. Jin O.,
    3. Rhinn M.,
    4. Daigle N.,
    5. Stevenson L.,
    6. Rossant J.
    (1996) A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. Development 122, 243–252
    OpenUrlAbstract
    1. Aparicio S.,
    2. Morrison A.,
    3. Gould A.,
    4. Gilthorpe J.,
    5. Chaudhuri C.,
    6. Rigby P.,
    7. Krumlauf R.,
    8. Brenner S.
    (1995) Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes. Proc. Nat. Acad. Sci. USA 92, 1684–1688
    OpenUrlAbstract/FREE Full Text
    1. Bally-Cuif L.,
    2. Gulisano M.,
    3. Broccoli V.,
    4. Boncinelli E.
    (1995) c-otx2 is expressed in two different phases of gastrulation and is sensitive to retinoic acid treatment in chick embryo. Mech. Dev 49, 49–63
    OpenUrlCrossRefPubMedWeb of Science
    1. Bliz I. L.,
    2. Cho K. W. Y.
    (1995) Anterior neuroectoderm is progressively induced during gastrulation: the role of the Xenopus homeobox gene orthodenticle. Development 121, 993–1004
    OpenUrlAbstract
    1. Brenner S.,
    2. Elgar G.,
    3. Sandford R.,
    4. Macrae A.,
    5. Venkatesh B.,
    6. Aparicio S.
    (1993) Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome. Nature 366, 265–268
    OpenUrlCrossRefPubMed
    1. Bulfone A.,
    2. Kim H.-J.,
    3. Puelles L.,
    4. Porteus M. H.,
    5. Grippo J. F.,
    6. Rubenstein J. L. R.
    (1993) The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the forebrain, face and limbs in midgestation mouse embryos. Mech. Dev 40, 129–140
    OpenUrlCrossRefPubMedWeb of Science
    1. Catron K. M.,
    2. Iler N.,
    3. Abate C.
    (1993) Nucleotides flanking a conserved TAAT core dictate the DNA binding specificity of three murine homeodomain proteins. Mol. Cell. Biol 13, 2354–2365
    OpenUrlAbstract/FREE Full Text
    1. Couly G. F.,
    2. Coltey P. M.,
    3. Le Douarin N. M.
    (1993) The triple origin of skull in higher vertebrates: a study in quail-chick chimeras. Development 117, 409–429
    OpenUrlAbstract
    1. Couly G.,
    2. Grapin-Botton A.,
    3. Coltey P.,
    4. Le Douarin N. M.
    (1996) The regeneration of the cephalic neural crest, a problem revisited: the regenerating cells originate from the contralateral or from the anterior and posterior neural fold. Development 122, 3393–3407
    OpenUrlAbstract
    1. Cserjesi P.,
    2. Lilly B.,
    3. Bryson L.,
    4. Wang Y.,
    5. Sassoon D. A.,
    6. Olson E. N.
    (1992) MHox: a mesodermally restricted homeodomain protein that binds an essential site in the muscle creatine kinase enhancer. Development 115, 1087–1101
    OpenUrlAbstract
    1. deBeer G. R.
    (1931) On the nature of the trabecula cranii. Q. J. Microsc. Sci 74, 701–731
    OpenUrl
    1. Dolle P.,
    2. Price M.,
    3. Duboule D.
    (1992) Expression of the murine Dlx-1 homeobox gene during facial, ocular and limb development. Differentiation 49, 93–99
    OpenUrlCrossRefPubMedWeb of Science
    1. Finkelstein R.,
    2. Perrimon N.
    (1991) The molecular genetics and head development in Drosophila melanogaster. Development 112, 899–912
    OpenUrlPubMedWeb of Science
    1. Gans C.,
    2. Northcutt R. G.
    (1983) Neural crest and the origin of vertebrates: A new head. Science 220, 268–274
    OpenUrlAbstract/FREE Full Text
    1. Gehring W. J.,
    2. Affolter M.,
    3. Burglin T.
    (1994) Homeodomain proteins. Annu. Rev. Biochem 63, 487–526
    OpenUrlCrossRefPubMedWeb of Science
    1. Imai H.,
    2. Osumi-Yamashita N.,
    3. Ninomiya Y.,
    4. Eto K.
    (1996) Contribution of early-emigrating midbrain crest cells to the dental mesenchyme of mandibular molar teeth in rat embryos. Dev. Biol 176, 151–165
    OpenUrlCrossRefPubMedWeb of Science
    1. Kasai Y.,
    2. Nambu J. R.,
    3. Lieberman P. M.,
    4. Crews S. T.
    (1992) Dorsal-ventral patterning in Drosophila: DNA binding of snail protein to the single-minded gene. Proc. Nat. Acad. Sci. USA 89, 3414–3418
    OpenUrlAbstract/FREE Full Text
    1. Köntges G.,
    2. Lumsden A.
    (1996) Rhombencephalic neural crest segmentation is preserved throughout craniofacial ontogeny. Development 122, 3229–3242
    OpenUrlAbstract
    1. Krumlauf R.
    (1994) Hox genes in vertebrate development. Cell 78, 191–201
    OpenUrlCrossRefPubMedWeb of Science
    1. Kuratani S.,
    2. Matsuo I.,
    3. Aizawa S.
    (1997) Developmental patterning and evolution of the mammalian viscerocranium: Genetic insights into comparative morphology. Dev. Dynam 209, 139–155
    OpenUrlCrossRefPubMedWeb of Science
    1. Li Y.,
    2. Allende M. L.,
    3. Finkelstein R.,
    4. Weinberg E. S.
    (1994) Expression of two zebrafish orthodenticle -related genes in the embryonic brain. Mech. Dev 48, 229–244
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Sprawson N.,
    3. Graham A.
    (1991) Segmental origin and migration of neural crest cells in the hindbrain region of the chick embryo. Development 113, 1281–1291
    OpenUrlAbstract
    1. MacKenzie A.,
    2. Leeming G. L.,
    3. Jowett A. K.,
    4. Ferguson M. W. J.,
    5. Sharpe P. T.
    (1991). The homeobox gene Hox-7.1 has specific regional and temporal expression patterns during early murine craniofacial embryogenesis, especially tooth development in vivo and in vitro. Development 111, 269–285
    OpenUrlAbstract
    1. Marshall H.,
    2. Studer M.,
    3. Pöpperl H.,
    4. Aparicio S.,
    5. Kuroiwa A.,
    6. Brenner S.,
    7. Krumlauf R.
    (1994) A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Nature 370, 567–571
    OpenUrlCrossRefPubMed
    1. Martin J. F.,
    2. Bradley A.,
    3. Olson E. N.
    (1995) The paired -like homeo box gene MHox is required for early events of skeletogenesis in multiple lineages. Genes Dev 9, 1237–1249
    OpenUrlAbstract/FREE Full Text
    1. Matsuo I.,
    2. Kitamura M.,
    3. Okazaki K.,
    4. Yasuda K.
    (1991) Binding of a factor to an enhancer element responsible for the tissue-specific expression of the chickenA-crystallin gene. Development 113, 539–550
    OpenUrlAbstract
    1. Matsuo I.,
    2. Kuratani S.,
    3. Kimura C.,
    4. Takeda N.,
    5. Aizawa S.
    (1995) Mouse Otx2 functions in the formation and patterning of rostral head. Genes Dev 9, 2646–2658
    OpenUrlAbstract/FREE Full Text
    1. Mercier P.,
    2. Simeone A.,
    3. Cotelli F.,
    4. Boncinelli E.
    (1995) Expression pattern of two otx genes suggests a role in specifying anterior body structures in zebrafish. Int. J. Dev. Biol 39, 559–573
    OpenUrlPubMedWeb of Science
    1. Nichols D. H.
    (1981) Neural crest formation in the head of the mouse embryos as observed using a new histological technique. J. Embryol. Exp. Morph 64, 105–120
    OpenUrlPubMedWeb of Science
    1. Noden D. M.
    (1975) An analysis of the migratory behavior of avian cephalic neural crest cells. Dev. Biol 42, 106–130
    OpenUrlCrossRefPubMedWeb of Science
    1. Noden D. M.
    (1988) Interactions and fates of avian craniofacial mesenchyme. Development 103, 121–140
    1. Osumi-Yamashita N.,
    2. Ninomiya Y.,
    3. Doi H.,
    4. Eto K.
    (1994) The contribution of both forebrain and midbrain crest cells to the mesenchyme in the frontonasal mass of mouse embryos. Dev. Biol 164, 409–419
    OpenUrlCrossRefPubMedWeb of Science
    1. Pannese M.,
    2. Polo C.,
    3. Andreazzoli M.,
    4. Vignali R.,
    5. Kablar B.,
    6. Barsacchi G.,
    7. Boncinelli E.
    (1995) The Xenopus homologue of Otx2 is a maternal homeobox gene that demarcates and specifies anterior body regions. Development 121, 707–720
    OpenUrlAbstract
    1. Pöpperl H.,
    2. Bienz M.,
    3. Studer M.,
    4. Chan S.-K.,
    5. Aparicio S.,
    6. Brenner S.,
    7. Mann R. S.,
    8. Krumlauf R.
    (1995) Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell 81, 1031–1042
    OpenUrlCrossRefPubMedWeb of Science
    1. Prince V.,
    2. Lumsden A.
    (1994) Hoxa-2 expression in normal andtransposed rhombomeres: independent regulation in the neural tube and crest. Development 120, 911–923
    OpenUrlAbstract
    1. Puelles L.,
    2. Rubenstein L. R.
    (1993) Expression patterns of homeobox and other putative regulatory genes in the embryonic mouse forebrain suggest a neuromeric organization. Trends Neurosci 16, 472–479
    OpenUrlCrossRefPubMedWeb of Science
    1. Qiu M.,
    2. Bulfone A.,
    3. Martinez S.,
    4. Meneses J. J.,
    5. Shimamura K.,
    6. Pedersen R. A.,
    7. Rubenstein J. L. R.
    (1995) 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 9, 2523–2538
    OpenUrlAbstract/FREE Full Text
    1. Rijli F. M.,
    2. Mark M.,
    3. Lakkaraju S.,
    4. Dierich A.,
    5. Dolle P.,
    6. Chambon P.
    (1993) A homeotic transformation is generated in the rostral branchial region of the head by disruption of Hoxa-2, which acts as a selector gene. Cell 75, 1333–1349
    OpenUrlCrossRefPubMedWeb of Science
    1. Satokata I.,
    2. Maas R.
    (1994) Msx1 deficient mice exhibit cleft palate and abnormalities craniofacial and tooth development. Nature Genetics 6, 348–355
    OpenUrlCrossRefPubMedWeb of Science
    1. Serbedzija G. N.,
    2. Bronner-Fraser M.,
    3. Fraser S. T.
    (1992) Vital dye analysis of cranial neural crest cell migration in the mouse embryo. Development 116, 297–307
    OpenUrlAbstract/FREE Full Text
    1. Shawlot W.,
    2. Behringer R. R.
    (1995) Requirement for Lim1 in head-organizer. Nature 374, 425–430
    OpenUrlCrossRefPubMed
    1. Simeone A.,
    2. Acampora D.,
    3. Gulisano M.,
    4. Stornaiuolo A.,
    5. Boncinelli E.
    (1992) Nested expression domains of four homeobox genes in developing rostral brain. Nature 358, 687–690
    OpenUrlCrossRefPubMed
    1. Simeone A.,
    2. Acampora D.,
    3. Mallamaci A.,
    4. Stornaiuolo A.,
    5. D'Apice M. R.,
    6. Nigro V.,
    7. Boncinelli E.
    (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
    OpenUrlPubMedWeb of Science
    1. Simeone A.,
    2. Avantaggiato V.,
    3. Moroni M. C.,
    4. Mavilio F.,
    5. Arra C.,
    6. Cotelli F.,
    7. Nigro V.,
    8. Acampora D.
    (1995) Retinoic acid induces stage-specific antero-posterior transformation of rostral central nervous system. Mech. Dev 51, 83–98
    OpenUrlCrossRefPubMedWeb of Science
    1. Zhao Q.,
    2. Behringer R. R.,
    3. de Crombrugghe B.
    (1996) Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene. Nature Genetics 13, 275–283
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells
C. Kimura, N. Takeda, M. Suzuki, M. Oshimura, S. Aizawa, I. Matsuo
Development 1997 124: 3929-3941;
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