Craniofacial Development and Stem cell biology, and Biomedical Research Centre, Dental Institute, King's College London, Guy's Hospital, London Bridge, London, UK.
Dev Dyn. 2012 Sep;241(9):1465-72. doi: 10.1002/dvdy.23828. Epub 2012 Jul 24.
Tooth development is known to be mediated by the cross-talk between signaling pathways, including Shh, Fgf, Bmp, and Wnt. MicroRNAs (miRNAs) are 19- to 25-nt noncoding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs, which is believed to be important for the fine-tuning signaling pathways in development. To investigate the role of miRNAs in tooth development, we examined mice with either mesenchymal (Wnt1Cre/Dicer(fl/fl)) or epithelial (ShhCre/Dicer(fl/fl)) conditional deletion of Dicer, which is essential for miRNA processing.
By using a CD1 genetic background for Wnt1Cre/Dicer(fl/fl), we were able to examine tooth development, because the mutants retained mandible and maxilla primordia. Wnt1Cre/Dicer(fl/fl) mice showed an arrest or absence of teeth development, which varied in frequency between incisors and molars. Extra incisor tooth formation was found in ShhCre/Dicer(fl/fl) mice, whereas molars showed no significant anomalies. Microarray and in situ hybridization analysis identified several miRNAs that showed differential expression between incisors and molars.
In tooth development, miRNAs thus play different roles in epithelium and mesenchyme, and in incisors and molars.
牙齿的发育是由信号通路之间的串扰介导的，包括 Shh、Fgf、Bmp 和 Wnt。microRNAs（miRNAs）是 19 到 25 个核苷酸的非编码小单链 RNA，通过与靶 mRNA 结合来负调控基因表达，这被认为对发育过程中信号通路的精细调节很重要。为了研究 miRNAs 在牙齿发育中的作用，我们检查了间质（Wnt1Cre/Dicer(fl/fl)）或上皮（ShhCre/Dicer(fl/fl)）中 Dicer 条件性缺失的小鼠，Dicer 对 miRNA 的加工是必不可少的。
通过使用 CD1 遗传背景的 Wnt1Cre/Dicer(fl/fl)，我们能够检查牙齿的发育，因为突变体保留了下颌和上颌原基。Wnt1Cre/Dicer(fl/fl) 小鼠的牙齿发育出现停滞或缺失，其频率在切牙和磨牙之间有所不同。ShhCre/Dicer(fl/fl) 小鼠出现额外的切牙形成，而磨牙没有明显的异常。微阵列和原位杂交分析确定了几个在切牙和磨牙之间表达差异的 miRNAs。
在牙齿发育过程中，miRNAs 因此在上皮和间充质以及切牙和磨牙中发挥不同的作用。
