Abstract
MicroRNAs are known to regulate gene function in many tissues and organs, but their expression and function, if any, in tooth development are elusive. We sought to identify them by microRNA screening analyses and reveal their overall roles by inactivating Dicer1 in the dental epithelium and mesenchyme. Discrete sets of microRNAs are expressed in molars compared with incisors as well as epithelium compared with mesenchyme. Conditional knockout (cKO) of Dicer1 (mature microRNAs) in the dental epithelium of the Pitx2-Cre mouse results in multiple and branched enamel-free incisors and cuspless molars, and change in incisor patterning and in incisor and molar size and shape. Analyses of differentiating dental epithelial markers reveal a defect in ameloblast differentiation. Conversely, the cervical loop (stem cell niche) is expanded in Dicer1 cKO. These results demonstrate that tooth development is tightly controlled by microRNAs and that specific microRNAs regulate tooth epithelial stem cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Ameloblasts / cytology*
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Amelogenesis / genetics*
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Amelogenesis / physiology
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Animals
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Body Patterning / genetics
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Cell Differentiation
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / physiology*
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Dental Enamel / abnormalities
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Enamel Organ / cytology*
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Endoribonucleases / genetics
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Endoribonucleases / physiology*
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Epithelium / embryology
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Epithelium / growth & development
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Gene Expression Profiling
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Gene Expression Regulation, Developmental
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Gene Knockout Techniques
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Homeobox Protein PITX2
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology
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Incisor / embryology
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Incisor / growth & development
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Mesoderm / embryology
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Mesoderm / growth & development
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Mice
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Mice, Knockout
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MicroRNAs / biosynthesis
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MicroRNAs / genetics
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MicroRNAs / physiology*
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Molar / embryology
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Molar / growth & development
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Oligonucleotide Array Sequence Analysis
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Ribonuclease III
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Stem Cell Niche
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Stem Cells / cytology
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Tooth Abnormalities / genetics
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Transcription Factors / genetics
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Transcription Factors / physiology
Substances
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Homeodomain Proteins
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MicroRNAs
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Transcription Factors
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Endoribonucleases
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Dicer1 protein, mouse
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Ribonuclease III
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DEAD-box RNA Helicases