Genome-wide analysis of gene expression in human embryonic tooth germ.

While numerous genes that play important regulatory roles during tooth development in mice have been identified, little is known about gene expression profile and their function during human odontogenesis. To unveil expression profile of odontogenic genes in humans, we conducted genome-wide gene expression analysis by microarray assays to analyze differential gene expression between tooth germ and lip tissue from 11-week old human fetuses. We identified 167 genes that are strongly expressed in the cap stage tooth germ as compared to the lip tissue. Among them, 145 genes were further identified by gene ontology enrichment analysis that are highly represented in multiple gene ontology classes, include extracellular components, sequence-specific DNA binding proteins, Wnt-protein binding molecules, system development, organogenesis, and cell differentiation. Sixty-seven genes that are known to be associated with mammalian tooth development and tooth abnormalities were identified. Real-time PCR was further employed to validate microarray data. Moreover, in situ hybridization assay demonstrated tooth type specific expression of ISL1 and BARX1 in the incisor, canine, and molar respectively, consistent with microarray results. Our results represent a set of reliable data that could provide a solid base for future elaboration of molecular mechanisms underlying human tooth development.