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MicroRNA 200c Targets Noggin Expression: A Role for MicroRNAs in Dental Epithelial Cell Differentiation

MicroRNAs are known to control gene expression patterns in other tissues and organs and in this report we demonstrate that craniofacial/tooth development is tightly controlled by microRNAs. To understand the role of microRNAs in tooth morphogenesis dental epithelial and mesenchyme tissue was screened for microRNA expression. There are specific sets of microRNAs expressed in the dental epithelium compared to the dental mesenchyme. Furthermore, specific microRNAs are expressed in incisors compared to molars revealing a code of microRNAs required for tooth development. Interestingly, bioinformatics analyses indicate only a small number of genes are regulated by microRNAs during late stages of tooth development. Conditional knockout (cKO) of Dicer1 (mature microRNAs) in the dental epithelium using the Pitx2‐Cre mouse results in multiple and branched enamel‐free incisors, a change in incisor patterning, and incisor and molar size and shape. Furthermore, deletion of oral epithelial microRNAs resulted in a cleft palate, revealing new mechanisms for their role in regulating palatogenesis. Epithelial microRNAs control incisor dental epithelial cell differentiation demonstrating a unique role for microRNAs in regulating in vivo dental stem cell biology. Noggin, a potent BMP inhibitor is up‐regulated in the Dicer1 knockout mouse, which prevents BMP signaling and cell differentiation. MicroRNA 200c targets Noggin to allow for normal tooth development and a mechanism to regulate cell differentiation. These results demonstrate a critical role for microRNAs in regulating tooth and craniofacial development through the dental stem cell niche and a mechanism involving microRNA 200c regulation of Noggin and BMP signaling. Support for this research was provided from grants DE13941 and DE18885 to BAA from the National Institute of Dental and Craniofacial Research.