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Session Schedule & Abstracts
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|Saturday 2nd July, 2016|
|Moderator(s): J. Richman, L. Hlusko, & T. Grieco|
DEN2-1 11:30 am Osr2 patterns the mammalian dentition through modulation of Wnt signaling. Kwon HJE, Cincinnati Children's Hospital Medical Center; Jia S, Cincinnati Children's Hospital Medical Center; Lan Y, Cincinnati Children's Hospital Medical Center; Zhou J, Cincinnati Children's Hospital Medical Center; Liu H, Cincinnati Children's Hospital Medical Center; Jiang R*, Cincinnati Children's Hospital Medical Center email@example.com |
Abstract: We previously reported that the transcription factor Osr2 is expressed in a buccolingual gradient across the molar tooth developmental field and restricts mouse molar tooth formation in a single row through suppression of propagation of the mesenchymal odontogenic activity by the Msx1-Bmp4 signaling pathway. Recently, we found that supernumerary tooth initiation in the Osr2-/- mice could occur in the absence of mesenchymal Bmp4. To elucidate further the molecular mechanism patterning the molar tooth field, we isolated developing tooth mesenchyme from the Osr2-/- and Msx1-/- mutant mouse embryos, respectively, and from their control littermates and carried out RNA-seq analyses. We found that expression of several genes encoding secreted Wnt antagonists, including Dkk2, Sfrp1, and Sfrp2, was significantly upregulated in the Msx1-/- tooth mesenchyme and significantly down-regulated in the Osr2-/- tooth mesenchyme. Remarkably, in situ hybridization analysis revealed that Dkk2 and Sfrp2 are preferentially expressed in the oral mesenchyme lingual to the developing molar tooth germs, in a pattern similar to that of Osr2 mRNA expression. Expression of both Dkk2 and Sfrp2 mRNAs was dramatically reduced in the oral mesenchyme immediately lingual to the molar tooth germs in Osr2-/- embryos but significantly expanded into the molar tooth mesenchyme in the Msx1-/- and Bmp4-deficient embryos. We found that in utero treatment with the Dkk inhibitor IIIC3 was sufficient to rescue mandibular molar morphogenesis in Bmp4-deficent mice but not in Msx1-/- mice. Whereas inactivation of Sfrp2 was also insufficient to rescue molar tooth morphogenesis in Msx1-/- mice, treatment of Msx1-/-Sfrp2-/-Sfrp3-/- compound mutant mice in utero with IIIC3 rescued maxillary molar morphogenesis. Together, these data indicate Osr2 and Msx1 interact to pattern the mouse molar tooth morphogenetic field through regulation of both Bmp4 and Wnt signaling. This work was supported by NIDCR grant DE018401.
DEN2-2 12:00 pm Development of the diphyodont dentition in minipigs. Buchtova M*, Institute of Animal Physiology and Genetics, Brno, Czech Republic; Dosedelova H, Institute of Animal Physiology and Genetics, Brno, Czech Republic; Department of Anatomy, Histology and Embryology, UVPS Brno, Czech Republic; Popa E, Department of Craniofacial Development and Stem Cell Biology, King's College London, Guy's Hospital London, UK; Putnova I, Institute of Animal Physiology and Genetics, Brno, Czech Republic; Stembirek J, Institute of Animal Physiology and Genetics, Brno, Czech Republic; Department of Experimental Biology, Masaryk University, Brno, Czech Republic; Department of Oral and Maxillofacial Surgery, University Hospital Ostrava, Czech Republic; Tucker AS, Department of Craniofacial Development and Stem Cell Biology, King's College London, Guy's Hospital London, UK firstname.lastname@example.org |
Abstract: Minipigs have a normodont diphyodont dentition without a diastema and exhibit numerous morphological similarities compared with the human dental pattern. They are therefore an excellent model for studying the mechanisms of replacement and patterning of heterodont teeth. All tooth germs in the minipig are initiated at the tip of the dental lamina. The dental lamina grows into the mesenchyme in a lingual direction, and its inclined growth is underlined by asymmetrical cell proliferation and expression of SOX2 and PCP proteins. Moreover, there are differences in growth intensity between dental and interdental areas of the lamina, with the interdental area lagging behind in development from an early stage. Loss of growth potential is characterised by a reduction in cell proliferation and down-regulation of the progenitor marker SOX2. Interestingly, the tip of the successional lamina is SOX2-negative in the dental area while its expression is expanded to the tip of the interdental lamina, indicating that the level of SOX2 expression may be linked to odontogenic potential. The successional dental lamina, which is necessary for permanent dentition formation, is apparent at the late bell stage with formation of a bud lingual to the deciduous tooth. At this stage, the superficial part of the dental lamina begins to fragment. Disintegration is initiated on the side facing the tooth anlagen while the opposite side is still proliferating and SOX2-positive. This pattern of fragmentation suggests that loss of the lamina may be triggered by signals from the deciduous tooth. Interestingly, only a few TUNEL positive cells were evident in the dental lamina during disintegration. In conclusion, minipigs provide an important experimental model to uncover developmental mechanisms contributing to the formation of replacement dentitions as well as providing a detailed analysis of the processes important in limiting the number of tooth generations in mammals. The research was supported by Grant Agency of Czech Republic (14-37368G to MB lab, 14-29273P to JS).
DEN2-3 12:15 pm Genetic and phenotypic modularity in the mammalian dental arcade. Hlusko LJ*, University of California Berkeley; Brasil MF, University of California Berkeley; Clay S, University of California Berkeley; Hoehna S, University of California Berkeley; Huelsenbeck J, University of California Berkeley; Huffman M, University of California Berkeley; Monson TA, University of California Berkeley; Takenaka R, University of California Berkeley; Schmitt CA, Boston University; Yoo S, University of California Berkeley; Mahaney MC, University of Texas Rio Grande Valley email@example.com |
Abstract: The dental arcade is essentially one organ system, but because it is comprised of individual teeth that develop and erupt over an extended period of ontogenetic time, we tend to conceptualize teeth as separate biological entities. For example, in cladistics analyses, biologists often include multiple dental traits, assuming them to be developmentally and genetically independent. Here, we describe over 15 years of research that explores variation across the mammalian dental arcade using a phenotype-back approach. In contrast to developmental genetics, which provides a gene-forward view of how genes influence and determine teeth, we employ analytical methods related to evolutionary quantitative genetics. These analyses yield results that enable us to redefine dental phenotypes that more accurately reflect the underlying genetic mechanisms that influence their variation. We will present results from our quantitative genetic analyses of dental variation in two pedigreed populations: mice and baboons. From these analyses, we developed hypotheses about genetic modularity in the mammalian dentition. We then tested these hypotheses using large phenotypic datasets of dental variation within and across primates, artiodactyls, and carnivores. By adding fossil data to these analyses, we then show how patterns of evolutionary change further strengthen support for our new phenotype definitions, and in so doing, yield insight to major taxonomic shifts in evolution. Funding was provided by NSF (BCS 0130277, 0500179, and 0616308). NIH provided support for the pedigreed baboon colony at the Southwest National Primate Research Center.
DEN2-4 12:45 pm Discerning genetic architecture from phenotypic covariance in human dentitions. Huffman M*, University of California, Berkeley; Brasil M, University of California, Berkeley; Monson T, University of California, Berkeley; Hlusko LJ, University of California, Berkeley firstname.lastname@example.org |
Abstract: Quantitative genetic analyses of dental variation in mice and baboons provide a set of hypotheses as to how human phenotypic variation will be patterned if underlain by the same genetic architecture. Phenotypic correlation matrices were calculated for humans (n=300), Old World monkeys (n=752), and apes (n=180) to test the hypothesis that these phenotypic correlation matrices will reflect the published genetic correlation matrices for baboons. We find that humans return lower phenotypic correlations on average compared to baboons and other Old World Monkeys, and consequently do not clearly reflect the same pattern of correlation. One possible explanation is that the genetic architecture of humans was disrupted (and therefore differs) because our dentitions are dwarfed compared to our fossil ancestors. For comparison, we estimated phenotypic correlations matrices for a sample of cervids (n=30) that included pudu, a dwarfed South American deer. The dwarfism hypothesis was not supported, as the results yielded high correlations (0.76-0.95) similar to baboons, and unlike what we found for humans. Phenotypic correlations are influenced by genetic and non-genetic factors. If the non-genetic influences are high, the underlying genetic architecture may be obscured. When Principal Component Analysis (PCA) was applied to all samples included in this study, results show that the latent structure of human dental variation clusters near our closest living relatives, and as such, appears to be influenced by the same genetic architecture. Correlation matrices may be too blunt of an instrument for discerning genetic architecture from phenotypic covariance in human dentitions.
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