The first mouse molar (M1) is the most common model for odontogenesis, with research particularly focused on prenatal development. However, the functional dentition forms postnatally, when the histogenesis and morphogenesis of the tooth is completed, the roots form and the tooth physically anchors into the jaw. In this work, M1 was studied from birth to eruption, assessing morphogenesis, proliferation and apoptosis, and correlating these with remodeling of the surrounding bony tissue. The M1 completed crown formation between postnatal (P) days 0-2, and the development of the tooth root was initiated at P4. From P2 until P12, cell proliferation in the dental epithelium reduced and shifted downward to the apical region of the forming root. In contrast, proliferation was maintained or increased in the mesenchymal cells of the dental follicle. At later stages, before tooth eruption (P20), cell proliferation suddenly ceased. This withdrawal from the cell cycle correlated with tooth mineralization and mesenchymal differentiation. Apoptosis was observed during all stages of M1 postnatal morphogenesis, playing a role in the removal of cells such as osteoblasts in the mandibular region and working together with osteoclasts to remodel the bone around the developing tooth. At more advanced developmental stages, apoptotic cells and bodies accumulated in the cell layers above the tooth cusps, in the path of eruption. Three-dimensional reconstruction of the developing postnatal tooth and bone indicates that the alveolar crypts form by resorption underneath the primordia, whereas the ridges form by active bone growth between the teeth and roots to form a functional complex.

Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Zobrazit více v PubMed

Andujar BM, Magloire H, Hartmann DJ, et al. Early mouse molar root development: cellular changes and distribution of fibronectin, laminin and type-IV collagen. Differentiation. 1985;30:111–122. PubMed

Benjamin M, Hillen B. Mechanical influences on cells, tissues and organs –‘mechanical morphogenesis’. Eur J Morphol. 2003;41:3–7. PubMed

Blechschmidt E. Mechanische Genwirkungen Funktionsentwicklung I. Göttingen: Musterschmidt; 1948.

Blechschmidt E. Anatomie und Ontogenese des Menschen. Heidelberg: Quelle&Meyer; 1978.

Blechschmidt E. In: The Ontogenetic Basis of Human Anatomy: The Biodynamic Approach to Development from Conception to Adulthood. Freeman B, editor. Berkeley: North Atlantic Books; 2004.

Böcker FW, Becker R. Zahnentwicklung und Kieferwachstum. Dtsch Zahnärztebl. 1965;19:454–462. PubMed

Bosshardt DD, Schroeder HE. Cementogenesis reviewed: a comparison between human premolars and rodent molars. Anat Rec. 1996;245:267–292. PubMed

Cerri PS, Katchburian E. Apoptosis in the epithelial cells of the rests of Malassez in the periodontium of rat molars. J Periodontal Res. 2005;40:365–372. PubMed

Cerri PS, Freymüller E, Katchburian E. Apoptosis in the early developing periodontium of rat molars. Anat Rec. 2000;258:136–144. PubMed

Cho M-I, Garant PR. Development and general structure of the periodontium. Periodontol 2000. 2000;24:9–27. PubMed

Diamond M, Applebaum E. The epithelial sheath: histogenesis and function. J Dent Res. 1942;21:403–411.

Diekwisch TGH. The developmental biology of cementum. Int J Dev Biol. 2001;45:695–706. PubMed

Diep L, Matalova E, Mitsiadis TA, et al. Contribution of the tooth bud mesenchyme to alveolar bone. J Exp Zool B Mol Dev Evol. 2009;312B:510–517. PubMed

Fleischmannova J, Matalova E, Tucker AS, et al. Mouse models of tooth abnormalities. Eur J Oral Sci. 2008;116:1–10. PubMed

Fleischmannova J, Matalova E, Sharpe PT, et al. Formation of the tooth–bone interface. J Dent Res. 2010;89:108–115. PubMed

Gaunt PN, Gaunt WA. Three Dimensional Reconstruction in Biology. London: Pitman Medical Publications; 1978.

Grant D, Bernick S. Morphodifferentiation and structure of Hertwig's root sheath in the cat. J Dent Res. 1971;50:1580–1588. PubMed

Gurling FG, Sampson WJ. Epithelial root-sheath changes during molar formation in the mouse. Arch Oral Biol. 1985;30:757–764. PubMed

Harada H, Mitsuyasu T, Toyono T, et al. Epithelial stem cells in teeth. Odontology. 2002;90:1–6. PubMed

Ingber DE. Mechanical control of tissue growth: function follows form. Proc Natl Acad Sci U S A. 2005;102:11571–11572. PubMed PMC

Jösten M, Rudolph R, Stein H, et al. Immun- und enzymhistochemische Differenzierung zwischen Geschwulst-Riesenzellen und osteoklastenähnlichen Riesenzellen in Neoplasien von Katze und Hunden am Paraffinschnitt. Berl Münch Tierärztl Wschr. 1993;106:390.

Kaneko H, Hashimoto S, Enokiya Y, et al. Cell proliferation and death of Hertwig's epithelial root sheath in the rat. Cell Tissue Res. 1999;298:95–103. PubMed

Lester KS. The incorporation of epithelial cells by cementum. J Ultrastruct Res. 1969;27:63–87. PubMed

Luan X, Yoshihiro I, Diekwisch TGH. Evolution and development of Hertwig's epithelial root sheath. Dev Dyn. 2006;235:1167–1180. PubMed PMC

Marks SC, Jr, Schroeder HE. Tooth eruption: theories and facts. Anat Rec. 1996;245:374–393. PubMed

Matalova E, Tucker AS, Sharpe P. Death in the Life of a Tooth. J Dent Res. 2004;83:11–16. PubMed

Norberg O. Untersuchungen über das dento-gingivale Epithelleistensystem im intrauterinen Leben des Menschen. Stockholm: A.-B. Fahlcrantz‘ Boktrykeri; 1929.

Norberg O. Die Morphogenese der primitiven Zahnalveolen beim Menschen und ihre Bedeutung für die Stellungsanomalien der Zähne. Anat Embryol. 1933;100:394–432.

Ohazama A, Courtney JM, Sharpe PT. Opg, Rank, and Rankl in tooth development: co-ordination of odontogenesis and osteogenesis. J Dent Res. 2004;83:241–244. PubMed

Pressnell JK, Schreibman MP. Humanson's Animal Tissue Techniques. Baltimore: The Johns Hopkins University Press; 1997.

Proffit WR, Frazier-Bowers SA. Mechanism and control of tooth eruption: overview and clinical implications. Orthod Craniofacial Res. 2009;12:59–63. PubMed

Radlanski RJ, Renz H. Genes, forces, and forms. Mechanical aspects during prenatal craniofacial development. Dev Dyn. 2006;235:1219–1229. PubMed

Radlanski RJ, Renz H, Klarkowski MC. Prenatal development of the human mandible. 3D reconstructions, morphometry, and bone remodelling pattern, stages 12-117 mm CRL. Anat Embryol. 2003;207:221–232. PubMed

Shimazu Y, Sato K, Aoyagi K, et al. Hertwig's epithelial cells and multi-root development of molars in mice. J Oral Biosci. 2009;51:210–217.

Silver FH, Siperko LM, Seehra GP. Mechanobiology of force transduction in dermal tissue. Skin Res Technol. 2003;9:3–23. PubMed

Slavkin HC, Bessem C, Fincham AG, et al. Human and mouse cementum proteins immunologically related to enamel proteins. Biochim Biophys Acta. 1989;991:12–18. PubMed

Sodek J, McKee MD. Molecular and cellular biology of alveolar bone. Periodontol 2000. 2000;2000:24. PubMed

Thesleff I, Sharpe P. Signaling networks regulating dental development. Mech Dev. 1997;67:111–123. PubMed

Thomas HF. Root formation. Int J Dev Biol. 1995;39:231–237. PubMed

Tucker A, Sharpe P. The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Gen. 2004;5:499–508. PubMed

Wentz FM, Weinmann JP, Schour I. The prevalence, distribution, and morphological changes of the epithelial remnants in the molar region of the rat. J Dent Res. 1950;29:637–646. PubMed

Wesselink PR, Beertsen W. The prevalence and distribution of rests of Malassez in the mouse molar and their possible role in repair and maintenance of the periodontal ligament. Arch Oral Biol. 1993;38:399–403. PubMed

Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res. 2008;87:414–434. PubMed PMC

Wise GE, Frazier-Bowers S, D'Souza RN. Cellular, molecular and genetic determinants of tooth eruption. Crit Rev Oral Biol Med. 2002;13:323–334. PubMed

Yen AH-H, Sharpe PT. Stem cells and tooth tissue engineering. Cell Tissue Res. 2008;331:359–372. PubMed

Yokohama-Tamaki T, Ohshima H, Fujiwara N, et al. Cessation of Fgf10 signaling, resulting in a defective dental epithelial stem cell compartment, leads to transition from crown to root formation. Development. 2006;133:1359–1366. PubMed

Zeichner-David M, Oishi K, Zhengyan S, et al. Role of Hertwig's epithelial root sheath cells in tooth root development. Dev Dyn. 2003;228:651–663. PubMed

Hypoxia-inducible factors in postnatal mouse molar dental pulp development: insights into expression patterns, localisation and metabolic pathways

Role of Cell Death in Cellular Processes During Odontogenesis

Formation and Developmental Specification of the Odontogenic and Osteogenic Mesenchymes

The Impact of the Eda Pathway on Tooth Root Development

Regulators of Collagen Fibrillogenesis during Molar Development in the Mouse

Non-apoptotic functions of caspase-7 during osteogenesis

Apoptotic signaling in mouse odontogenesis