Abstract
BackgroundOur current knowledge of tooth development derives mainly from studies in mice, which have only one set of non-replaced teeth, compared with the diphyodont dentition in humans. The miniature pig is also diphyodont, making it a valuable alternative model for understanding human tooth development and replacement. However, little is known about gene expression and function during swine odontogenesis. The goal of this study is to undertake the survey of differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs. The identification of genes related to diphyodont development should lead to a better understanding of morphogenetic patterns and the mechanisms of diphyodont replacement in large animal models and humans.ResultsThe temporal gene expression profiles during early diphyodont development in miniature pigs were detected with the Affymetrix Porcine GeneChip. The gene expression data were further evaluated by ANOVA as well as pathway and STC analyses. A total of 2,053 genes were detected with differential expression. Several signal pathways and 151 genes were then identified through the construction of pathway and signal networks.ConclusionsThe gene expression profiles indicated that spatio-temporal down-regulation patterns of gene expression were predominant; while, both dynamic activation and inhibition of pathways occurred during the morphogenesis of diphyodont dentition. Our study offers a mechanistic framework for understanding dynamic gene regulation of early diphyodont development and provides a molecular basis for studying teeth development, replacement, and regeneration in miniature pigs.
Highlights
Our current knowledge of tooth development derives mainly from studies in mice, which have only one set of non-replaced teeth, compared with the diphyodont dentition in humans
The results indicated that the last deciduous molar in the mandible of the miniature pig undergoes cap stage at embryonic day 40 (E40), bell stage at E50, secretory stage at E60, and its successional tooth is derived from the lingual successional dental lamina, which is visible at E50 when its deciduous counterpart is in bell stage, and changes little in morphology at E60 (Figure 1A)
The more changes in transcription between E50 and E40 implied that more gene variations were involved in Third deciduous molar (Dm3) morphogenesis from cap stage to bell stage as well as the appearance of sdl The results showed the genes were predominantly down-regulated on E50 versus E40; while, up-regulated genes dominated the morphogenesis of tooth germs on E60 versus E50
Summary
Our current knowledge of tooth development derives mainly from studies in mice, which have only one set of non-replaced teeth, compared with the diphyodont dentition in humans. The miniature pig is diphyodont, making it a valuable alternative model for understanding human tooth development and replacement. The goal of this study is to undertake the survey of differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs. The identification of genes related to diphyodont development should lead to a better understanding of morphogenetic patterns and the mechanisms of diphyodont replacement in large animal models and humans. Swine would serve as excellent pre-clinical experiment alternatives for tooth development and regeneration compared with the rodent models widely used. The porcine genome project was completed [24,25,26,27,28,29,30,31,32,33]; further analysis of the mechanisms of morphogenetic patterns and diphyodont replacement should be possible using molecular methods in this large animal model
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