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Introduction: Prevalence of childhood obesity is at an all-time high. The effect of childhood obesity on dental development and eruption is a widespread topic today in the dental field. Several cross-sectional studies over the past decade have found an association between advanced dental development and eruption and childhood obesity. The purpose of this study is to examine the longitudinal relationship between childhood Body Mass Index (BMI), and the development of the permanent dentition. Methods: 76 subjects from a longitudinal dataset (Iowa Facial Growth Study 1946-1960) were selected to examine the relationship between BMI and dental development during childhood. Periapical and lateral cephalometric radiographs were used to provide a dental maturity score for each subject using the Demirjian et al. (1973) method at three separate time points (age 4, 8, and 12). BMI was calculated using subjects’ height and weight at each time point. Results: Children with higher BMI’s at all three time points (4, 8 and 12) tended to have advanced dental development compared to children who were of normal weight status. Children who were considered underweight (< 5th BMI percentile) were more likely to be dentally delayed. BMI at age 4 was predictive of dental development status at age 8 and 12. Conclusion: Our results add to the growing body of evidence that childhood obesity is associated with advanced dental development. This is important in the dental and orthodontic fields, as early eruption has been hypothesized to be associated with increased dental caries, crowding, and malocclusions.

An evolution in methods of identifying the causal mutations and candidate genes for Mendelian disorders has occurred recently. Though several studies have reported the causative mutations in non syndromic tooth agenesis, there are only two reports on autosomal recessive nonsyndromic tooth agenesis in consanguineous families. Since the consanguinity rate is high in tribal population of Saudi and Pakistan, this study identified consanguineous families in these populations to investigate the molecular basis of tooth agenesis. This study aimed to study the phenotype of familial tooth agenesis in Saudi and Pakistani families of consanguineous marriage, and to identify the causative mutations. A further aim was to investigate the influence of the agenesis gene on tooth size in one large Saudi family. Sixteen families with non-syndromic tooth agenesis, were clinically characterised for the pattern of inheritance, tooth agenesis severity and type of teeth affected. Genetic analysis including homozygosity mapping and exome sequencing was performed in eight families. Hand measurements of Saudi family tooth dimensions were made on dental study models. The most affected tooth type in studied families were the lower second premolar and upper lateral incisors. The homozygosity mapping approach failed to identify the regions of the diseased mutations in these families. The exome sequencing data revealed a heterozygous novel frameshift mutation in exon 2 of the MSX1 gene, c.750_751insACCGGCTGCC (p.A250fs) in one Saudi family and a homozygous novel mutation in exon 8 of the SMOC2 gene, c.681T>A (p.C227X), in the Pakistani family. It was found that there was a significant (p <.0.05) trend of reduction in the crown sizes both in the tooth agenesis group and their family members with no tooth agenesis compared to the control group. It is concluded that homozygosity mapping was not sensitive to identify the elusive tooth agenesis gene and whole exome sequencing technique is needed in future studies. The tooth measurement study indicates and confirms that crown size is closely related to tooth agensis.

The estimation of age at time of death is often an important step in the identification of human remains. If this age can be accurately estimated, it will significantly narrow the field of possible identities that will have to be compared to the remains in order to establish a positive identification. Some of the more accurate methods of age estimation, in the juvenile and younger adult, have been based on the assessment of the degree of dental development as it relates to chronological age. The purpose of this current study was to test the applicability of one such system, the Demirjian system, to a Sydney sample population, and to develop and test age prediction models using a large sample of Sydney children (1624 girls, 1637 boys). The use of the Demirjian standards resulted in consistent overestimates of chronological age in children under the age of 14 years by as much as a mean of 0.97 years, and underestimates of chronological age in children over 14 years by as much as a mean of 2.18 years in 16 year-old females. Of the alternative predictive models derived from the Sydney sample, those that provided the most accurate age estimates are applicable for the age ranges 2-14 years, with a coefficient of determination value of R-square=0.94 and a 95% confidence interval of �1.8 years. The Sydney based standards provided significantly different and more accurate estimates of age for that sample when compared to the published standards of Demirjian.

The estimation of age at time of death is often an important step in the identification of human remains. If this age can be accurately estimated, it will significantly narrow the field of possible identities that will have to be compared to the remains in order to establish a positive identification. Some of the more accurate methods of age estimation, in the juvenile and younger adult, have been based on the assessment of the degree of dental development as it relates to chronological age. The purpose of this current study was to test the applicability of one such system, the Demirjian system, to a Sydney sample population, and to develop and test age prediction models using a large sample of Sydney children (1624 girls, 1637 boys). The use of the Demirjian standards resulted in consistent overestimates of chronological age in children under the age of 14 years by as much as a mean of 0.97 years, and underestimates of chronological age in children over 14 years by as much as a mean of 2.18 years in 16 year-old females. Of the alternative predictive models derived from the Sydney sample, those that provided the most accurate age estimates are applicable for the age ranges 2-14 years, with a coefficient of determination value of R-square=0.94 and a 95% confidence interval of �1.8 years. The Sydney based standards provided significantly different and more accurate estimates of age for that sample when compared to the published standards of Demirjian.

Across vertebrates, the coordinated evolution and synchronous development of teeth and the mandible must require specific timing and positioning of gene expression. While debate persists about whether teeth have evolved before or after mandible, currently, the consensus is that these systems evolved at separate times and thus have discreet origins. This raises an important question of whether tooth and mandibular tissues have over the course of their evolution become developmentally co-dependent or, as separate evolutionary origins would imply, remain developmentally autonomous of each other. The molecular signaling that patterns the genesis of upper versus lower jaw skeletons, as well as specifies tooth type (i.e., molar vs. incisor) is relatively well understood. To date, the distinct genetic processes that drive tooth development distinct from jaw skeletal development has been little-studied, in no small part due to the technical complexity of this task. The main hypothesis of thesis is that a collection of genes acting within a gene regulatory network (GRN) drives odontogenesis with neither input from, nor influence on, jaw morphogenesis. The Transformation Related Protein (TRP63) is a master transcription factor that is vital to odontogenesis because TRP63 maintains the competence and proliferation of the epithelial layer of the tooth organ. Thus the “toothless” TRP63 homozygote mouse mutant (Brdm2 mutant) fails to develop teeth even though it develops a virtually unperturbed mandible. This combination of lower jaw morphogenesis in the absence of odontogenesis presents a rare model to study the genetic changes that occur when teeth but not jaws fail to form. A previous microarray gene expression analysis (Boughner laboratory, unpublished data) of mandibular prominences (MdPs) derived from embryonic day (E) 10-13 revealed that, compared to heterozygote (Trp63+/-) MdPs, in Brdm2 mutant MdPs, transcript levels of cerebellin 1 (Cbln1); keratin 2-8 (Krt2-8); phospholipid transfer protein (Pltp) and fermitin 1 (Fermt1) were altered in at least some of the four embryonic stages. Specifically Cbln1 and Krt2-8 were up-regulated while Pltp and Fermt1 were down-regulated. None of these four genes have previously been linked to odontogenesis yet all are potential candidates for a “tooth-specific” GRN. Using RT-qPCR analysis, I aimed to test the validity of the microarray work and confirmed its veracity by showing that, generally, Cbln1 and Krt2-8 mRNA were up-regulated, while Fermt1 (but not Trp63 or Pltp) mRNA was significantly down-regulated in the MdPs of Brdm2 mutant mice relative to Trp63+/- mice. Conversely, western blotting protein expression analysis showed little-to-no change among Brdm2 MdPs relative to either wild type (Trp63 +/+) or Trp63+/- embryos, making it difficult to tease out the precise relationship between CBLN1, FERMT1, KRT2-8, and PLTP and TRP63. These results show a lack of strong correlation between mRNA and protein expression. Because the mRNA analyses showed disturbances in the expression level in a few of these five genes within the MdPs during the earliest stages of tooth development, these genes remain candidates for an odonto-specific GRN. In complement to the genetic work, to characterize the tandem developmental morphology of tooth and jaw skeleton tissues, my work included developing a new tissue staining protocol. Using Protargol, a silver-based compound, to enhance in uncut mouse embryos contrast among tiny, soft oral tissues and visualize their organization in 3D and microscopic detail across several embryonic stages. This novel protocol offers a simple, easy-to-follow, and relatively inexpensive way to effectively stain whole embryos aged E10-15 for X-ray based micro-computed tomography (μ-CT) imaging using synchrotron and desktop scanning systems. Because the scan data are digital, this new method also allows more precise, accurate and rapid empirical studies of the sizes, shapes and positions of teeth as they form within the jaw to clarify how these tissues are integrated as they develop. The work presented in this thesis investigated tooth development exclusive of mandible development from complementary molecular and morphological points of view. Driven by the lack of understanding of the genetic mechanisms that orchestrate tooth with jaw skeletal development, this study has for the first time isolated a set of genes that are potential candidates for tooth formation only. These results set the stage for next steps in testing the developmental-genetics that enable teeth and jaws to “fit” together as they develop.

No / Paleoanthropological studies often center on teeth, not only because these elements are commonly preserved in the fossil record, but because they apparently contain a wealth of information with regard to development, phylogeny, and function. However, despite a plethora of studies, somefundamental problems are still unresolved. For example, while it is recognized that the 3-dimensional arrangement of enamel prisms may hold important information with regard to phylogeny (von Koenigswald and Sander, 1997) and function (Rensberger, 2000), many paleoanthropological studies have thus far relied on investigating enamel microanatomy as a 2-dimensional structure (e.g., Dean et al., 2001 C Dean, M.G Leakey, D Reid, F Schrenk, G.T Schwartz, C Stringer and A Walker, Growth processes in teeth distinguish modern humans from Homo erectus an earlier hominins, Nature 414 (2001), pp. 628¿631. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (120)Dean et al., 2001). This is mainly due to difficulties in visualizing and quantifying the 3-D structure of prisms. In order to overcome these limitations a computer model was developed (Jiang et al., 2003) which attempted to simulate the effects of biophysical processes governing enamel formation in modern humans (adapted from Osborn, 1970). Here we extend our model and present preliminary data on inter-specific variation in prism arrangement among primates. Furthermore, during our work torecreate the 3D microstructure of prismatic enamel it became increasingly clear that there are not only limitations with previous dental growth studies, but that these studies are based on fundamentally different concepts regarding evolutionary processes from those assumed in our approach. These limitations and differences will be highlighted also.

Laboratory mouse is a appropriate experimental model for studies on normal tooth development mechanisms and for understanding of etio-pathogenesis of dental anomalies in humans. Mouse dentition consists of one incisor separated from three molars by toothless diastema in each jaw quadrant. Although an adult mice diastema does not contain teeth, rudimentary tooth primordia (MS, R2) appear here during embryonic development. However, their development stops and consequently functional tooth does not arise here. It is known that in mice with mutations in Spry2 and Spry4 genes, supernumerary teeth arise in antemolar region. The understanding of the temporo-spatial dynamics of signaling centers in Spry2/Spry4 double transgenic mice may help to elucidate the role of these embryonic diastemal buds in supernumerary tooth formation. The research of possible regeneration of dental anomalies in off-spring of crossing Spry4 deficient mice with supernumerary teeth formation with Eda deficient mice with predisposition to reduced dentition could be the way to elucidating of mechanism of dental pathologies development in general. Our aim was to describe temporal and spatial dynamics of Shh signaling domains in Spry2/Spry4 embryos, because Shh is one of the markers of early odontogenesis and determining of...

A odontologia moderna, mesmo usando as suas técnicas mais primorosas, na prática, ainda recupera a perda dental com implantes metálicos recobertos por coroas protéticas. Há um empenho coletivo dos cientistas em criar técnicas de desenvolvimento dental in vitro na busca por maneiras de recuperar, de maneira biológica, a ausência dental. Já é possível criar estruturas similares a dentes a partir de células-tronco de origem dental (polpa de dentes permanentes e decíduos) e não dental (células-tronco embrionárias, células-tronco da medula óssea e da crista neural) por meio de recombinação dos tecidos epiteliais e mesenquimais de germes dentais. As técnicas de reconstrução tecidual nunca estiveram tão perto do desenvolvimento da terceira dentição mas a ciência ainda tem muito a aprender no que concerne o estudo da biologia dental e engenharia de tecidos. Não basta saber como um dente se desenvolve; há de se entender como ele interage com o organismo do qual faz ou fará parte. É com esta preocupação que nos propomos a estudar se pode haver uma correlação entre o desenvolvimento do sistema nervoso e vascular de um germe dental transplantado com a posição que ele é implantado e/ou com a presença de tecido ósseo que no leito receptor. Ademais, buscamos saber se o estágio de desenvolvimento do germe dental a ser transplantado pode influenciar a formação de tecido nervoso e vascular na polpa dental ou não. Nossos resultados revelaram que o local do sítio do implante influencia diretamente o desenvolvimento dental e que isto é tempo dependente. A vascularização e a reinervação da polpa dental nos espécimes implantados nas tíbias é mais semelhante ao grupo controle que os implantados nos rins e isto independe da posição de implantação dental. Entretanto, a polpa dental dos germes implantados nos rins parece estar comumente mais sadia, conter mais odontoblastos viáveis e ser capaz de produzir tecidos mineralizados como a osteodentina. / Contemporary dentistry, even using modern techniques, still deal with missing teeth using metal implants coated by prosthetic crowns. However, there is a worldwide effort to develop a biotooth using in vitro techniques. In this way it is already possible to generate structures similar to teeth using recombination of odontogenic and non odontogenic cells in tissue engineering experiments. The transplant of the recombined cells into a host is a necessary and major step to obtain the biotooth. In this context, at the same time that the development of an appropriate sensorial and vascular system in the biotooh is required, there are many unclear questions about it. Therefore, herein we intend to analyze (I) whether may exist a correlation between the stage of development and vascular and nervous re-growth in the dental pulp after tooth transplantation; (II) if the absence or presence of bone could influence this processes or (III) if the position of implantation could change the vascular and/or nervous development in the transplanted tooth. Our results showed that the site of implantation directly alter tooth development modifying morphogenesis and expression of different vascular, perivascular and neural markers in a time dependant way. The re-growth of the vascular and neural tissue on samples transplanted to the tibia is more similar to the control group than the kidney ones and it is non dependant of the position of implantation. However, the pulp tissue of the samples transplanted under the kidney capsule seemed to be healthier as they were capable of producing mineralized tissue such as osteodentin and still had live odontoblasts.