Failure of tooth formation mediated by miR-135a overexpression via BMP signaling

Micrornas (mirnas) are known to regulate a variety of gene functions in many tissues and organs,but their expression and function in tooth development are not well-understood. a specific mirna,mir-135a,was determined to be highly expressed at the bud stage. interestingly,after the cap stage,mir-135a was expressed in the epithelium and mesenchyme but not in the inner enamel epithelium. to identify the relationship between mir-135a and its putative target genes,bmpr-ia and bmpr-ib,in early tooth development,mir-135a was ectopically overexpressed with a lentivirus. this overexpression resulted in the repression of bmpr-ia and bmpr-ib. furthermore,mir-135a inhibited both bmpr-ia and bmpr-ib transcription. bmp2 proteins were expressed ectopically in tooth germs during the cap stage to determine the relationship between mir-135a and bmp signaling in early tooth development. when mir-135a was ectopically expressed,no tooth formation was observed after 4 wk of incubation in the kidney capsule. this study suggested that bmp signaling,specifically bmpr-ia and bmpr-ib,regulates tooth formation via mir-135a. © international & american associations for dental research.