Tooth morphogenesis and ameloblast differentiation are regulated by micro-RNAs
Tooth morphogenesis and ameloblast differentiation are regulated by micro-RNAs
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DOI：
10.1016/j.ydbio.2010.01.019
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Thesleff, Irma
中科院分区：
文献类型：
--
作者：
Michon, Frederic;Tummers, Mark;Thesleff, Irma
牙齿作为外胚层的附属物，其形态发生受保守信号通路网络介导的组织相互作用的调节。Micro-RNA(MiRNA)途径已成为胚胎发育各个方面的重要调节因子，但其在牙齿发育中的作用尚不清楚。我们发现，在牙齿形态发生和牙细胞分化过程中，RNAi通路效应分子的表达是动态的。基于芯片图谱，我们选择了8个在形态发生过程中表达的miRNAs和7个在包含干细胞巢的切牙颈部环中表达的miRNAs。这些miRNAs主要在牙齿上皮细胞中表达。DCR(K14-/-)上皮细胞中DICER-1的条件性缺失导致了牙齿形状和釉质形成的轻微但显著的异常。DCR(K14-/-)磨牙牙冠的尖状图案类似于祖先鼠类啮齿动物和具有调制信号通路的小鼠突变体的图案。在DCR(K14-/-)切牙上，唇侧表面形成纵沟，这是由于颈环中的前体上皮异位萌发所致。此外，成釉细胞分化受损，导致磨牙和门牙釉质形成不足。为了帮助筛选出牙齿丰富的miRNAs的候选靶基因，我们构建了一个新的面向外胚层器官的数据库miRTooth。所选择的miRNAs的预测靶点包括调控牙齿发育的主要形态发生信号通路的几个组成部分。根据我们的发现，我们认为miRNAs主要通过微调保守的信号网络来调控牙齿的形态发生，并且miRNAs可能在牙齿进化过程中发挥了重要作用。(C)2010 Elsevier Inc.保留所有权利。
Teeth form as appendages of the ectoderm and their morphogenesis is regulated by tissue interactions mediated by networks of conserved signal pathways. Micro-RNA (miRNA) pathway has emerged as important regulator of various aspects of embryonic development, but its function in odontogenesis has not been elucidated. We show that the expression of RNAi pathway effectors is dynamic during tooth morphogenesis and differentiation of dental cells. Based on microarray profiling we selected 8 miRNAs expressed during morphogenesis and 7 miRNAs in the incisor cervical loop containing the stem cell niche. These miRNAs were mainly expressed in the dental epithelium. Conditional deletion of Dicer-1 in the epithelium (Dcr(K14-/-)) resulted in rather mild but significant aberrations in tooth shape and enamel formation. The cusp patterns of the Dcr(K14-/-) molar crowns resembled the patterns of both ancestral muroid rodents and mouse mutants with modulated signal pathways. In the Dcr(K14-/-) incisors, longitudinal grooves formed on the labial surface and these were shown to result from ectopic budding of the progenitor epithelium in the cervical loop. In addition, ameloblast differentiation was impaired and resulted in deficient enamel formation in molars and incisors. To help the identification of candidate target genes of the selected tooth enriched miRNAs, we constructed a new ectodermal organ oriented database, miRTooth. The predicted targets of the selected miRNAs included several components of the main morphogenetic signal pathways regulating tooth development. Based on our findings we suggest that miRNAs modulate tooth morphogenesis largely by fine tuning conserved signaling networks and that miRNAs may have played important roles during tooth evolution. (C) 2010 Elsevier Inc. All rights reserved.