Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 W. Holcombe Boulevard, Houston, TX 77030, USA.
J Dent Res. 2010 Aug;89(8):779-84. doi: 10.1177/0022034510369304. Epub 2010 May 26.
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.
MicroRNAs 已知在许多组织和器官中调节基因功能,但它们在牙齿发育中的表达和功能(如果有的话)仍然难以捉摸。我们试图通过 microRNA 筛选分析来识别它们,并通过在牙上皮和间充质中失活 Dicer1 来揭示它们的总体作用。与切牙相比,磨牙以及与间充质相比,牙上皮中表达的 microRNAs 种类不同。Pitx2-Cre 小鼠的牙上皮中 Dicer1(成熟 microRNAs)的条件性敲除(cKO)导致多个分叉的无釉质切牙和无尖磨牙,以及切牙模式和切牙和磨牙大小和形状的改变。分化牙上皮标记物的分析显示釉质细胞分化缺陷。相反,Dicer1 cKO 中颈环(干细胞巢)扩大。这些结果表明,牙齿发育受到 microRNAs 的严格控制,并且特定的 microRNAs 调节牙齿上皮干细胞分化。