Mammalian dentition exhibits distinct heterodonty, with more simple teeth located in the anterior area of the jaw and more complex teeth situated posteriorly. While some region-specific differences in signalling have been described previously, here we performed a comprehensive analysis of gene expression at the early stages of odontogenesis to obtain complete knowledge of the signalling pathways involved in early jaw patterning. Gene expression was analysed separately on anterior and posterior areas of the lower jaw at two early stages (E11.5 and E12.5) of odontogenesis. Gene expression profiling revealed distinct region-specific expression patterns in mouse mandibles, including several known BMP and FGF signalling members and we also identified several new molecules exhibiting significant differences in expression along the anterior-posterior axis, which potentially can play the role during incisor and molar specification. Next, we followed one of the anterior molecules, SATB2, which was expressed not only in the anterior mesenchyme where incisor germs are initiated, however, we uncovered a distinct SATB2-positive region in the mesenchyme closely surrounding molars. Satb2-deficient animals demonstrated defective incisor development confirming a crucial role of SATB2 in formation of anterior teeth. On the other hand, ectopic tooth germs were observed in the molar area indicating differential effect of Satb2-deficiency in individual jaw regions. In conclusion, our data provide a rich source of fundamental information, which can be used to determine molecular regulation driving early embryonic jaw patterning and serve for a deeper understanding of molecular signalling directed towards incisor and molar development.

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Stomatology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Stomatology St Anne's University Hospital Brno Czech Republic

Laboratory of Computed Tomography CEITEC BUT Brno Czech Republic

Laboratory of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Molecular Morphogenesis Institute of Animal Physiology and Genetics v v i Czech Academy of Sciences Veveri 97 602 00 Brno Czech Republic

Zobrazit více v PubMed

Rossant, J. & Tam, P.

Thesleff, I. & Tummers, M. Tooth organogenesis and regeneration. Stembook (2009) 10.3824/STEMBOOK.1.37.1. PubMed

Stockton, D. W., Das, P., Goldenberg, M., D’Souza, R. N. & Patel, P. I. Mutation of PAX9 is associated with oligodontia. PubMed DOI

Vastardis, H., Karimbux, N., Guthua, S. W., Seidman, J. G. & Seidman, C. E. A human MSX1 homeodomain missense mutation causes selective tooth agenesis. PubMed DOI

Mostowska, A., Biedziak, B. & Jagodzinski, P. P. Novel MSX1 mutation in a family with autosomal-dominant hypodontia of second premolars and third molars. PubMed DOI

Thomas, B. L., Liu, J. K., Rubenstein, J. L. R. & Sharpe, P. T. Independent regulation of Dlx2 expression in the epithelium and mesenchyme of the first branchial arch. PubMed DOI

Thomas, B. L. PubMed DOI

Satokata, I. & Maas, R. Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. PubMed DOI

Du, W., Du, W. & Yu, H. The role of fibroblast growth factors in tooth development and incisor renewal. PubMed DOI PMC

Miletich, I., Buchner, G. & Sharpe, P. T. Barx1 and evolutionary changes in feeding. PubMed DOI PMC

Elmubarak, N. A. R. Genetic risk of talon cusp: Talon cusp in five siblings. PubMed DOI PMC

Segura-Egea, J. J., Jiménez-Rubio, A., Ríos-Santos, J. V. & Velasco-Ortega, E. Dens evaginatus of anterior teeth (talon cusp): Report of five cases. PubMed

Gardner, D. G. & Girgis, S. S. Talon cusps: A dental anomaly in the Rubinstein-Taybi syndrome. PubMed DOI

Chen, R. J. & Chen, H. S. Talon cusp in primary dentition. PubMed DOI

Hattab, F. N., Yassin, O. M. & Sasa, I. S. Oral manifestations of Ellis-van Creveld syndrome: Report of two siblings with unusual dental anomalies. PubMed

Kjær, I. Dental approach to craniofacial syndromes: How can developmental fields show us a new way to understand pathogenesis?. PubMed DOI PMC

Buchtová, M. PubMed DOI

Sehic, A., Risnes, S., Khan, Q. E. S., Khuu, C. & Osmundsen, H. Gene expression and dental enamel structure in developing mouse incisor. PubMed DOI

Tarca, A. L., Romero, R. & Draghici, S. Analysis of microarray experiments of gene expression profiling. PubMed DOI PMC

van IJzendoorn, D. G. P. PubMed DOI PMC

Soldatov, R. PubMed DOI

Nimmagadda, S. PubMed DOI

Dobreva, G. PubMed DOI

Tucker, A. S., Matthews, K. L. & Sharpe, P. T. Transformation of tooth type induced by inhibition of BMP signaling. PubMed DOI

Mitsiadis, T. A. PubMed DOI

Tissier-Seta, J. P. PubMed DOI

Kim, B. M. PubMed DOI

Krivicka-Uzkurele, B., Pilmane, M. & Akota, I. Barx1, growth factors and apoptosis in facial tissue of children with clefts (2008). PubMed

Cobourne, M. T. & Sharpe, P. T. Tooth and jaw: Molecular mechanisms of patterning in the first branchial arch. PubMed DOI

Suryadeva, S. & Begum, M. Role of homeobox genes in tooth morphogenesis: A review. PubMed PMC

Gray, P. A. PubMed DOI

Tripodi, M., Filosa, A., Armentano, M. & Studer, M. The COUP-TF nuclear receptors regulate cell migration in the mammalian basal forebrain. PubMed DOI

Bergeron, K. F. PubMed DOI PMC

Kaiwar, C. PubMed DOI PMC

Barske, L. PubMed DOI PMC

Reymond, A. PubMed DOI

Shamblott, M. J., Bugg, E. M., Lawler, A. M. & Gearhart, J. D. Craniofacial abnormalities resulting from targeted disruption of the murine Sim2 gene. PubMed DOI

Ma, Q., Anderson, D. J. & Fritzsch, B. Neurogenin 1 null mutant ears develop fewer, morphologically normal hair cells in smaller sensory epithelia devoid of innervation. PubMed DOI PMC

Sudiwala, S. & Knox, S. M. The emerging role of cranial nerves in shaping craniofacial development. PubMed DOI PMC

Ten Berge, D. PubMed DOI

Sharpe, P. T. Homeobox genes and orofacial development. PubMed DOI

Twigg, S. R. F. PubMed DOI PMC

Beverdam, A., Brouwer, A., Reijnen, M., Korving, J. & Meijlink, F. Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. PubMed DOI

Jowett, A. K., Vainio, S., Ferguson, M. W. J., Sharpe, P. T. & Thesleff, I. Epithelial-mesenchymal interactions are required for msx 1 and msx 2 gene expression in the developing murine molar tooth. PubMed DOI

Liang, J. PubMed DOI PMC

Milet, C. & Monsoro-Burq, A. H. Neural crest induction at the neural plate border in vertebrates. PubMed DOI

Nakatomi, M. PubMed DOI

Molla, M. PubMed DOI PMC

Alappat, S., Zhang, Z. Y. & Chen, Y. P. Msx homeobox gene family and craniofacial development. PubMed DOI

Xu, Y. PubMed DOI PMC

Tamura, M. & Nemoto, E. Role of the Wnt signaling molecules in the tooth. PubMed DOI PMC

Niida, A. PubMed DOI

Brugmann, S. A. PubMed DOI

Zhang, Y. PubMed DOI PMC

Järvinen, E., Shimomura-Kuroki, J., Balic, A., Jussila, M. & Thesleff, I. Mesenchymal Wnt/β-catenin signaling limits tooth number. PubMed DOI

Lee, M. J., Kim, E. J., Li, L. & Jung, H. S. Roles of Wnt inhibitory factor 1 during tooth morphogenesis. PubMed DOI

Sasaki, T. PubMed DOI

Yamada, W. PubMed DOI

Dasgupta, K. PubMed DOI PMC

Palmer, A. J., Savery, D., Massa, V., Copp, A. J. & Greene, N. D. E. Genetic interaction of Pax3 mutation and canonical Wnt signaling modulates neural tube defects and neural crest abnormalities. PubMed DOI

Bandyopadhyay, S., Prasad, S. & Singhania, P. K. Partial anodontia in a case of Waardenburg’s syndrome. PubMed DOI

Sólia-Nasser, L. PubMed DOI PMC

Krüger, J. M. PubMed DOI PMC

Diez-Roux, G. PubMed DOI PMC

Bell, R. A. V. PubMed DOI PMC

Gyorgy, A. B., Szemes, M., De Juan Romero, C., Tarabykin, V. & Agoston, D. V. SATB2 interacts with chromatin-remodeling molecules in differentiating cortical neurons. PubMed DOI

Dobreva, G., Dambacher, J. & Grosschedl, R. SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin μ gene expression. PubMed DOI PMC

Zhao, X. PubMed DOI

He, L. PubMed DOI PMC

FitzPatrick, D. R. PubMed DOI

Leoyklang, P. PubMed DOI

Rosenfeld, J. A. PubMed DOI PMC

Döcker, D. PubMed DOI PMC

Seong, B. K. A. PubMed DOI

Scott, J. PubMed DOI

Peterková, R. PubMed DOI

Peterkova, R., Lesot, H. & Peterka, M. Phylogenetic memory of developing mammalian dentition. PubMed DOI

Klein, O. D. PubMed DOI PMC

Klein, O. D. PubMed DOI PMC

Kurosaka, H. PubMed DOI

Li, X., Ye, X. & Su, J. The dental phenotype of primary dentition in SATB2-associated syndrome: A report of three cases and literature review. PubMed DOI PMC

Mouillé, M. PubMed DOI PMC

Zarate, Y. A., Bosanko, K., Derar, N. & Fish, J. L. Abnormalities in pharyngeal arch-derived structures in SATB2-associated syndrome. PubMed DOI PMC

Dosedělová, H. PubMed DOI PMC

Prochazka, J. PubMed DOI PMC

Ohazama, A. PubMed DOI PMC

Zhang, Q. PubMed DOI

Ohazama, A. PubMed DOI PMC

Cobourne, M. T. & Sharpe, P. T. Making up the numbers: The molecular control of mammalian dental formula. PubMed DOI

Carvalho, B. S. & Irizarry, R. A. A framework for oligonucleotide microarray preprocessing. PubMed DOI PMC

Ritchie, M. E. PubMed DOI PMC

Huber, W. PubMed DOI PMC

Dai, M. PubMed DOI PMC

Cunningham, F. PubMed DOI PMC

Bolstad, B. M. Low-level analysis of high-density oligonucleotide array data: Background, normalization and summarization (2004).

Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. DOI

Sarkans, U. PubMed DOI PMC