Advertisement
JOURNAL ARTICLES
Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition
B.L. Thomas, A.S. Tucker, M. Qui, C.A. Ferguson, Z. Hardcastle, J.L. Rubenstein, P.T. Sharpe
Development 1997 124: 4811-4818;

Summary

The molecular events of odontogenic induction are beginning to be elucidated, but until now nothing was known about the molecular basis of the patterning of the dentition. A role for Dlx-1 and Dlx-2 genes in patterning of the dentition has been proposed with the genes envisaged as participating in an ‘odontogenic homeobox gene code’ by specifying molar development. This proposal was based on the restricted expression of the genes in molar ectomesenchyme derived from cranial neural crest cells prior to tooth initiation. Mice with targeted null mutations of both Dlx-1 and Dlx-2 homeobox genes do not develop maxillary molar teeth but incisors and mandibular molars are normal. We have carried out heterologous recombinations between mutant and wild-type maxillary epithelium and mesenchyme and show that the ectomesenchyme underlying the maxillary molar epithelium has lost its odontogenic potential. Using molecular markers of branchial arch neural crest (Barx1) and commitment to chondrogenic differentiation (Sox9), we show that this population alters its fate from odontogenic to become chondrogenic. These results provide evidence that a subpopulation of cranial neural crest is specified as odontogenic by Dlx-1 and Dlx-2 genes. Loss of function of these genes results in reprogramming of this population of ectomesenchyme cells into chondrocytes. This is the first indication that the development of different shaped teeth at different positions in the jaws is determined by independent genetic pathways.

REFERENCES

    1. Bitgood M. J.,
    2. McMahon A. P.
    (1995) Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev. Biol 172, 126–138
    OpenUrlCrossRefPubMedWeb of Science
    1. 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. Butler P. M.
    (1956) The ontogeny of molar pattern. Biol. Rev 31, 30–70
    OpenUrlCrossRef
    1. Chen Y. P.,
    2. Bei M.,
    3. Woo I.,
    4. Satokata I.,
    5. Maas R.
    (1996) Msx-1 controls inductive signalling in mammalian tooth morphogenesis. Development 122, 3035–3044
    OpenUrlAbstract
    1. Ferrari D.,
    2. Sumay I.,
    3. Gannon J.,
    4. Sun H.L.,
    5. Brown A.M.C.,
    6. Upholt W.B.,
    7. Kosher A.A.
    (1995) The expression pattern of the Distal-less homeobox-containing gene Dlx-5 in the developing chick limb bud suggests its involvement in apical ectodermal ridge activity, pattern-formation, and cartilage differentiation. Mech Dev 52, 257–264
    OpenUrlCrossRefPubMedWeb of Science
    1. Goodrich L. V.,
    2. Johnson R. L.,
    3. Milenkovic L.,
    4. McMahon J. A.,
    5. Scott M. P.
    (1996) Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 10, 301–312
    OpenUrlAbstract/FREE Full Text
    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. Kollar E. J.,
    2. Baird G. R.
    (1969) The influence of the dental papilla on the development of tooth shape in embryonic mouse tooth germs. J. Embryol. Exp. Morphol 21, 131–.
    OpenUrlPubMedWeb of Science
    1. Lumsden A. G. S.
    (1988) Spatial organisation of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ. Development 103, 155–169
    1. Lyons K. M.,
    2. Pelton R. W.,
    3. Lyons B. L. M.
    (1990) Organogenesis and pattern formation in the mouse: RNA distribuiton patterns suggest a role for Bone Morphogenetic Protein-2A (BMP-2A). Development 109, 833–844
    OpenUrlAbstract/FREE Full Text
    1. Mackenzie A.,
    2. Leeming G. L.,
    3. Jowett A. K.,
    4. Fergusin 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. Mahmood R.,
    2. Bresnick J.,
    3. Hornbruch A.,
    4. Mahony C.,
    5. Morton N.,
    6. Colquhoun K.,
    7. Martin P.,
    8. Lumsden A.,
    9. Dickson C.,
    10. Mason I.
    (1995) A role for Fgf-8 in the initiation and maintenance of vertebrate limb bud outgrowth. Curr. Biol 5, 797–806
    OpenUrlCrossRefPubMedWeb of Science
    1. McGuinness T.,
    2. Porteus M. H.,
    3. Smiga S.,
    4. Bulfone A.,
    5. Kingsley C.,
    6. Qiu M.,
    7. Liu J.K.,
    8. Long J. E.,
    9. Xu D.,
    10. Rubenstein J. L. R.
    (1996) Sequence, orgAnisation and transcription of the Dlx-1 and Dlx-2 locus. Genomics 35, 473–485
    OpenUrlCrossRefPubMedWeb of Science
    1. Ng L. J.,
    2. Wheatley S.,
    3. Muscat G. E. O.,
    4. Conway Campbell J.,
    5. Bowles J.,
    6. Wright E.,
    7. Bell D. M.,
    8. Tam P. P. L.,
    9. Cheah K. S. E.,
    10. Koopman P.
    (1997) SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev. Biol 183, 108–121
    OpenUrlCrossRefPubMedWeb of Science
    1. Noden D. M.
    (1983) The role of the neural crest in patterning of avian cranial skeletal, connective and muscle tissues. Dev. Biol 96, 144–165
    OpenUrlCrossRefPubMedWeb of Science
    1. Özcelick T.,
    2. Porteus M. H.,
    3. Rubenstein J. L. R.,
    4. Francke U.
    (1992) DLX2 (TES1), a homeobox gene of the Distal-less family, assigned toconserved regions on human and mouse chromosomes 2. Genomics 13, 1157–1161
    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. Robinson G. W.,
    2. Mahon K. A.
    (1994) Differential and overlapping expression domains of Dlx-2 and Dlx-3 suggest distinct roles for Distal-less homeobox genes in craniofacial development. Mech. Dev 48, 199–215
    OpenUrlCrossRefPubMedWeb of Science
    1. Satokata I.,
    2. Maas R.
    (1994) Msx-1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nature Gen 6, 348–356
    OpenUrlCrossRefPubMedWeb of Science
    1. Saxen L.
    (1966) The effect of tetracycline on osteogenesis i n vitro. J. Exp. Zool 162, 269–294
    OpenUrlCrossRef
    1. Sharpe P. T.
    (1995) Homeobox genes and orofacial development. Conn. Tiss. Res 32, 17–25
    OpenUrlCrossRefPubMedWeb of Science
    1. Simeone A.,
    2. Acampora D.,
    3. Pannese M.,
    4. D'Esposito M.,
    5. Stornaiuolo A.,
    6. Gulisano M.,
    7. Mallamaci A.,
    8. Kastury K.,
    9. Druck T.,
    10. Huebner K.,
    11. Boncinelli E.
    (1994) Cloning and characterisation of two members of the vertebrate Dlx gene family. Proc. Natl. Acad. Sci USA 91, 2250–2254
    OpenUrlAbstract/FREE Full Text
    1. Thesleff I.,
    2. Vaahtokari A.,
    3. Partanen A.-M.
    (1995) Common molecular mechanisms regulating the development of teeth and other organs. Int. J. Dev. Biol 39, 35–50
    OpenUrlPubMedWeb of Science
    1. Tissier-Seta J.-P.,
    2. Mucchielli M.-L.,
    3. Mark M.,
    4. Mattei M.-G.,
    5. Goridis C.,
    6. Bruney J.-F.
    (1995) Barx1, a new mouse homeodomain transcription factor expressed in craniofacial ectomesenchyme and the stomach. Mech. Dev 51, 3–15
    OpenUrlCrossRefPubMedWeb of Science
    1. Trowel O. A.
    (1959) The culture of mature organs in a synthetic medium. Exp. Cell Res 16, 118–147
    OpenUrlCrossRefPubMedWeb of Science
    1. Vainio S.,
    2. Karavanova I.,
    3. Jowett A.,
    4. Thesleff I.
    (1993) Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75, 45–58
    OpenUrlCrossRefPubMedWeb of Science
    1. van Genderen C.,
    2. Okamura R. M.,
    3. Farinas I.,
    4. Quo R. G.,
    5. Parslow T. G.,
    6. Bruhn L.,
    7. Grosschedl R.
    (1994) Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in Lef-1 deficient mice. Genes Dev 8, 2691–2703
    OpenUrlAbstract/FREE Full Text
    1. Wright E.,
    2. Hargrave M. R.,
    3. Christiansen J.,
    4. Cooper L.,
    5. Kun J.,
    6. Evans T.,
    7. Gangadharan U.,
    8. Greenfield A.,
    9. Koopman P.
    (1995) The Sry -related gene Sox9 is expressed during chondrogenesis in mouse embryos. Nature Gen 9, 15–20
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition
B.L. Thomas, A.S. Tucker, M. Qui, C.A. Ferguson, Z. Hardcastle, J.L. Rubenstein, P.T. Sharpe
Development 1997 124: 4811-4818;
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