Signaling Modulation by During Tooth Morphogenesis in Mice.

miRNAs are conserved short non-coding RNAs that play a role in the modulation of various biological pathways during tissue and organ morphogenesis. In this study, the function of in tooth development, through its loss or gain in function was evaluated. A variety of techniques were utilized to evaluate detailed functional roles of during odontogenesis, including tooth cultivation, renal capsule transplantation, hybridization, real-time PCR, and immunohistochemistry. Two-day tooth cultivation at E13 identified altered cellular events, including cellular proliferation, apoptosis, adhesion, and cytoskeletal arrangement, with the loss and gain of . qPCR analysis revealed alterations in gene expression of tooth-related signaling molecules, including β, , , , , and , when inhibited with and mimic. Also, the inhibition of demonstrated increased mesenchymal localizations of pSMAD1/5/8, alongside decreased expression patterns of and within inner enamel epithelium (IEE) in E13 + 2 days cultivated teeth. Moreover, 1-week renal transplantation of cultivated teeth had smaller tooth size with reduced enamel and dentin matrices, along with increased cellular proliferation and expression along the Hertwig epithelial root sheath (HERS), within the inhibitor group. Similarly, in 3-week renal calcified teeth, the overexpression of did not affect tooth phenotype, while the loss of function resulted in long and slender teeth with short mesiodistal length. This study provides evidence that a suitable level of is required for the modulation of major signaling pathways, including Wnt, Bmp, and , during tooth morphogenesis.