ODONTOGENESIS- A HIGHLY COMPLEX CELL-CELL INTERACTION PROCESS

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1 ODONTOGENESIS- A HIGHLY COMPLEX CELL-CELL INTERACTION PROCESS AMBRISH KAUSHAL, MALA KAMBOJ Department of Oral and Maxillofacial Pathology Career Post Graduate Institute of Dental Sciences and Hospital Address: C-1111, Indiranagar, Opp.St. Dominic Church, Lucknow India malskam@gmail.com Abstract: - Odontogenesis is a highly co-ordinated and complex process which relies upon cell-cell interactions that result in the initiation and generation of tooth. Molecular changes that correlate with advancing tooth morphogenesis have been mapped by many research groups. Here, we review some of the current literature concerning molecular regulation of odontogenesis. Key-Words: - Odontogenesis; tooth formation, cell-cell interaction, molecular basis 1 Introduction Organogenesis is a complex process in which as a result of several instructive and permissive cellular interactions, there appears new cell strains, precise modifications of extracellular matrix, morphological and topographical changes and new tissue functions [1]. Tooth is undoubtedly one of the most complete and most useful of such tissue. 2 An Overview of Odontogenesis It is the formation and development of teeth. It can be divided into three overlapping phases viz. initiation, morphogenesis and histodifferentiation. During initiation, the oral epithelium folds inwards to form tooth germs and the site of tooth development. Then undifferentiated mesenchymal cells migrate to the site of tooth formation and proliferate to determine the shape of tooth during the morphogenesis phase. During histodifferentiation, cells proceeds to give rise to the mature dental tissue [2,3] (Fig. 1). It was discovered that epithelialmesenchymal interactions are sequential, i.e. there is a chain of interactive events that gradually govern advancing development. The interactions were also shown to be reciprocal occurring in both directions between epithelial and mesenchymal tissues. In tissue recombination experiments where epithelia and mesenchymes from different organs were cultured together, it was observed that, depending on the organ and its developmental stage, either the epithelium or the mesenchyme possessed the information for organ specific morphogenesis and differentiation. In the tooth, the early dental epithelium was shown to possess the potential to induce non-dental, neural crest derived mesenchyme to form tooth specific structures, which synthesized enamel proteins. The mesenchymal cell condensates in the developing teeth most closely resemble those in derivatives of the skin in which the mesenchymal cells form papillary structures surrounded by epithelial cells [2] (Fig. 2). It was found that simple medium like buffered Ph conditions and essential nutrients are permissive for complex processes while initiating the in vitro culture during mid gestation. For example E14/15 mouse molar tooth explants express multiple ISSN: ISBN:

2 cusps, dentine and enamel tissue specific biomineralization and even root formation in serumless medium. It was assumed that endogenous growth factors (including vitamin like molecules) provide the essential cues required for complex development in these artificial environment[1]. 3 Discussion It is conceivable that unique combinations of morphogens and transcription factors, which are involved in the establishment of the primary body plan, may also regulate the patterning in early development. Transcription factors are DNA binding proteins that control the activity of other genes. There are several groups of transcription factors containing conserved DNA sequences, such as homeoboxes, paired boxes, and zinc finger coding motifs. Some transcription factors, including DLX- 1, DLX-2 are expressed in the thickened presumptive dental epithelium suggesting that they may be downstream target genes for the morphogens and homeobox genes determining the sites of initiation. LEF-1 was shown to be the necessary regulatory molecule for tooth development as in the LEF-1 knockout mouse mutant teeth were missing. The homeobox containing genes Msx-1and Msx-2 are expressed in early tooth rudiment and their distributions suggest patterning functions during early tooth morphogenesis. The lack of Msx-1 gene in knockout mice resulted in the formation of cleft palate, and their teeth did not developed beyond the bud stage [2]. Barx-1 is another homeobox gene containing transcription factor that exhibits regionalized expression within the ectomesenchyme of the first branchial arch. Prior to the primary epithelial thickening Barx-1 is expressed in posterior regions of the first branchial arch mesenchyme, the region of future molar development. There is no Barx-1 expression in the anterior regions 3. Osteoprotegrin (OPG), receptor activator of nuclear factor-κb (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. It was analyzed that these three genes were expressed in murine odontogenesis from epithelial thickening to cytodifferentiation stage. Opg showed expression in the thickening and bud epithelium. Expression of Opg and RANK was observed in both the internal and external enamel epithelium as well as in the dental papilla mesenchyme. Although RANKl expression was not detected in the tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germ. The addition of exogenous OPG to explants cultures of tooth primordial produced a delay in tooth development that resulted in reduced mineralization. Therefore it was presumed that the spatiotemporal expression of these molecules in early tooth and bone primordial cells had a role in co-coordinating bone and tooth development[4] (Fig. 3). Collagen constitutes nearly 34% of the total ECM proteins and type I and III collagens are the most predominant types. Type I collagen, most commonly found in dense conjunctive tissues, is necessary for tissue architecture stabilization, while type III collagen, most commonly found in loose conjunctive tissues, has an important function in tissue elasticity. Type I collagen is the most abundant protein in mineralized tissues, except for enamel, and is also the main ECM organic component. In the study done on the maxilla and mandibles aging from week of intrauterine life of 9 human fetuses, it was found that type III collagen was detected in all specimens while type I collagen was present in focal areas of the dental papilla only in some specimens. Therefore, type III collagen is a regular component of the papillae of human tooth germs whereas type I collagen is present in a significantly lesser amount 5. Origin of odontogenic neoplasms, hamartomas and cysts: The origin of epithelial odontogenic neoplasms, hamartomas and cysts are bound up with the discussion of the parent cells of these lesions. Current viewpoints on the cytodifferentiation and histopathogenesis of ISSN: ISBN:

3 these lesions are today still largely based on morphology of, and co-localizations between the above odontogenic lesions and the developing tooth. An approach along the lines of investigating molecular regulation of the development of both the human teeth and the epithelial odontogenic neoplasms, hamartomas and cysts, is awaited with considerable interest, and will undoubtedly modify or enlarge our knowledge in this field [6,7]. 4 Conclusion The study of odontogenesis is providing insight into the developmental control mechanisms that operate at the molecular level during embryogenesis. The developing tooth provides one of the most useful experimental models for the study of induction and patterning mechanisms that are involved during organ morphogenesis. As our knowledge of these tissue interactions is extended, it should be stressed that odontogenic lesions is solely based on morphological comparisons with the developing tooth, thus allowing only hypothetical or theoretical reflections to be taken. It is expected that the explosion of cytogenetic and molecular genetic information over the past decade will in years to come have a significant impact on our understanding of the biology of the odontogenic lesions. [4] Ohazama A, Courtney J M, Sharpe P T. Opg, Rank and Rankl in tooth development: Co-ordination of odontogenesis and osteogenesis, J Dent Res, 83(3), 2004, [5] Abrahao I J, Martins M D, Katayama E, Antoniazzi J H, Segmentilli A, Marques M M. collagen analysis in human tooth germ papillae Braz Dent J,17(3), 2006, [6] Philipsen H P, Reichart P A. The development and fate of epithelial residues after completion of the human odontogenesis with special reference to the origin of epithelial odontogenic neoplasms, hamartomas and cysts; Oral Biosci Med, 2004, S [7] Tencate A R. The experimental investigation of odontogenesis; Int J Dev Biol, 39,1995, References: [1] Arechaga J. The tooth as a model in organogenesis, Int J Dev Biol, 39, 1995, [2] Theselff I, Vaahtokari A, Partanen A M. Regulation of organogenesis. Common molecular mechanisms regulating the development of teeth and other organs, Int J Dev Biol 39, 1995, [3] Cobourne M T. The genetic control of early Odontogenesis, British Journal of Orthodontics, 26(1), 1999, ISSN: ISBN:

Table 1: Selected cases of epithelial odontogenic neoplasms, hamartomas and cysts according to morphological studies (Reichart and Philipsen, 2004; Shear, 1992) Fig.

4 Table 1: Selected cases of epithelial odontogenic neoplasms, hamartomas and cysts according to morphological studies (Reichart and Philipsen, 2004; Shear, 1992) Fig. 1: Result of Odontogenesis: Source of odontogenic epithelium Dental lamina Lesion Oral epithelium Reduced Enamel Epithelium Rests of Malassez Ameloblastoma s S/MA + Desmoplastic (DA) + Peripheral (PA) + + Unicystic Fig. 2: Molecular control of tooth formation SOT CEOT + AOT + KCOT + + OGEH + Inflam. Paradent. Cyst ISSN: ISBN:

5 Fig. 3: Diagrammatic representation of Opg, Rank, and Rankl expression in early tooth development and proposed interaction between RANK and RANKL. (A) Expression of Opg, Rank, and Rankl in epithelium shown in blue and in mesenchyme in red. (B) Relationship between RANKL in dentary bone mesenchymal cells and RANK and OPG in tooth germ. ISSN: ISBN:

06 Tooth Development and Eruption

+ 06 Tooth Development and Eruption Tooth development Root development PDL and alveolar bone development Primary tooth eruption and shedding Permanent tooth eruption Q. Where and how tooth starts to form?