Gas1 Regulates Patterning of the Murine and Human Dentitions through Sonic Hedgehog

The mammalian dentition is a serially homogeneous structure that exhibits wide numerical and morphological variation among multiple different species. Patterning of the dentition is achieved through complex reiterative molecular signaling interactions that occur throughout the process of odontogenesis. The secreted signaling molecule Sonic hedgehog (Shh) plays a key role in this process, and the Shh coreceptor growth arrest-specific 1 (Gas1) is expressed in odontogenic mesenchyme and epithelium during multiple stages of tooth development. We show that mice engineered with Gas1 loss-of-function mutation have variation in number, morphology, and size of teeth within their molar dentition. Specifically, supernumerary teeth with variable morphology are present mesial to the first molar with high penetrance, while molar teeth are characterized by the presence of both additional and absent cusps, combined with reduced dimensions and exacerbated by the presence of a supernumerary tooth. We demonstrate that the supernumerary tooth in Gas1 mutant mice arises through proliferation and survival of vestigial tooth germs and that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt and downstream FGF signaling in odontogenic epithelium through facilitation of Shh signal transduction. Moreover, regulation of tooth number is independent of the additional Hedgehog coreceptors Cdon and Boc, which are also expressed in multiple regions of the developing tooth germ. Interestingly, further reduction of Hedgehog pathway activity in Shhtm6Amc hypomorphic mice leads to fusion of the molar field and reduced prevalence of supernumerary teeth in a Gas1 mutant background. Finally, we demonstrate defective coronal morphology and reduced coronal dimensions in the molar dentition of human subjects identified with pathogenic mutations in GAS1 and SHH/GAS1, suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.

Spatiotemporal Changes in Transcriptome of Odontogenic and Non-odontogenic Regions in the Dental Arch of Mus musculus

Over the past 40 years, studies on tooth regeneration have been conducted. These studies comprised two main flows: some focused on epithelial–mesenchymal interaction in the odontogenic region, whereas others focused on creating a supernumerary tooth in the non-odontogenic region. Recently, the scope of the research has moved from conventional gene modification and molecular therapy to genome and transcriptome sequencing analyses. However, these sequencing data have been produced only in the odontogenic region. We provide RNA-Seq data of not only the odontogenic region but also the non-odontogenic region, which loses tooth-forming capacity during development and remains a rudiment. Sequencing data were collected from mouse embryos at three different stages of tooth development. These data will expand our understanding of tooth development and will help in designing developmental and regenerative studies from a new perspective.

Maxillary Dentigerous Cyst with Double Wolf Teeth in a 3-Year-Old Quarter Horse Mare

Dentigerous cysts are characterised by the formation of cysts containing dental material with a variable level of development. They are the result of a distinct embryological phenomenon. Usually, they are of significant clinical relevance in horses, especially in tandem with ectopic tooth. Contrarily, supernumerary teeth or typical polyodontias usually have limited impact. In this case report, we describe the occurrence of a supernumerary first premolar (Triadan 105). Dissimilar to known scientific literature however was the formation of a cystic structure around the supernumerary tooth. Surgical removal of the dentigerous cyst is discussed, as are the possible causes for the formation of the cystic structure. Based on this case report, we suspect that the formation of a cystic structure may not be limited to atypical polyodontias, as they may also occur in supernumerary teeth.

Supernumerary tooth in nasopalatine canal: a rare cause of septal cartilage collapse

Mesiodens is the most common type of supernumerary tooth, located between the maxillary central incisors in close relation to the nasopalatine canal. A 20-year-old man presented with right-sided nasal blockage, nasal discharge and collapsed nose without history of trauma. Imaging revealed a calcified mass in the inferior meatus extending into dilated nasopalatine canal. Endoscopic removal of the mass revealed tuberculate appearance of an incompletely developed tooth, consistent with mesiodens. Based on the history of septal cartilage collapse with right-sided mucopurulent discharge, endoscopic findings of the right inferior turbinate being adherent to the septal cartilage and the underlying mesiodens, we believe that the patient developed a septal abscess secondary to infection in nasal mucosa surrounding the mesiodens causing collapse of septal cartilage. While a tooth or tooth-like mass causing nasal passage air-flow obstruction is uncommon, we believe that this is the first reported case of mesiodens presenting with septal cartilage collapse.

Characterization of Odontoblasts in Supernumerary Tooth-derived Dental Pulp Stem Cells between Passages by Real-Time PCR

The aim of this study is to compare the properties of odontoblast gene of early passage cells and late passage cells derived from impacted maxillary supernumerary teeth. Impacted supernumerary teeth with maxilla were extracted from 12 patients (8 males, 4 females) between 6 - 9 years old without medical history. Real-time polymerase chain reaction (PCR) was conducted to compare characterization of odontoblast cell in the 3rd and 10th passage, and between with bone inducing additive group and without additive group. Genes for odontoblasts characteristics are osteonectin (ONT), alkaline phosphatase (ALP), osteocalcin (OCN), dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP). The level of gene expression was in a decreasing order of ONT, ALP, OCN, DMP-1 and DSPP in the 3rd passage, and in decreasing order of ONT, DMP-1, OCN, ALP, and DSPP in the 10th passage in the undifferentiation and differentiation group. The order of ONT, DMP-1, and OCN did not changed. ALP and DMP-1 were switched in order. ALP and DMP-1 may be used as important markers for differentiating between the 3rd passage and 10th passage cells. Considering that supernumerary tooth was extracted young age and the time required to cultured 10th passage was short, supernumerary tooth can be considered a useful donor site of dental pulp stem cells.