Department of Operative Dentistry and Endodontics, College of Stomatology, The Fourth Military Medical University, Xi'an, P.R. China.
J Dent Res. 2012 Jul;91(7):690-5. doi: 10.1177/0022034512448660. Epub 2012 May 16.
Several Bmp genes are expressed in the developing mouse tooth germ from the initiation to the late-differentiation stages, and play pivotal roles in multiple steps of tooth development. In this study, we investigated the requirement of BMP activity in early tooth development by transgenic overexpression of the extracellular BMP antagonist Noggin. We show that overexpression of Noggin in the dental epithelium at the tooth initiation stage arrests tooth development at the lamina/early-bud stage. This phenotype is coupled with a significantly reduced level of cell proliferation rate and a down-regulation of Cyclin-D1 expression, specifically in the dental epithelium. Despite unaltered expression of genes known to be implicated in early tooth development in the dental mesenchyme and dental epithelium of transgenic embryos, the expression of Pitx2, a molecular marker for the dental epithelium, became down-regulated, suggesting the loss of odontogenic fate in the transgenic dental epithelium. Our results reveal a novel role for BMP signaling in the progression of tooth development from the lamina stage to the bud stage by regulating cell proliferation and by maintaining odontogenic fate of the dental epithelium.
在牙齿发生的起始到晚期分化阶段，多个 Bmp 基因在发育中的小鼠牙胚中表达，并在牙齿发育的多个步骤中发挥关键作用。在这项研究中，我们通过过表达细胞外 BMP 拮抗剂 Noggin 来研究 BMP 活性在早期牙齿发育中的需求。我们发现，在牙齿起始阶段牙上皮中 Noggin 的过表达将牙齿发育阻滞在釉板/早期芽期。这种表型与细胞增殖率的显著降低以及细胞周期蛋白 D1 表达的下调相关，特别是在牙上皮中。尽管牙间充质和转基因胚胎牙上皮中已知参与早期牙齿发育的基因表达不变，但 Pitx2 的表达下调，提示转基因牙上皮中的成牙命运丧失。我们的结果揭示了 BMP 信号在从釉板期到芽期的牙齿发育进展中的新作用，通过调节细胞增殖和维持牙上皮的成牙命运。
