Institute of Biotechnology, University of Helsinki, Helsinki FI-00014, Finland.
Department of Orofacial Sciences, University of California, San Francisco, CA 94143.
Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2300374120. doi: 10.1073/pnas.2300374120. Epub 2023 Jun 12.
When evolution leads to differences in body size, organs generally scale along. A well-known example of the tight relationship between organ and body size is the scaling of mammalian molar teeth. To investigate how teeth scale during development and evolution, we compared molar development from initiation through final size in the mouse and the rat. Whereas the linear dimensions of the rat molars are twice that of the mouse molars, their shapes are largely the same. Here, we focus on the first lower molars that are considered the most reliable dental proxy for size-related patterns due to their low within-species variability. We found that scaling of the molars starts early, and that the rat molar is patterned equally as fast but in a larger size than the mouse molar. Using transcriptomics, we discovered that a known regulator of body size, insulin-like growth factor 1 (), is more highly expressed in the rat molars compared to the mouse molars. Ex vivo and in vivo mouse models demonstrated that modulation of the IGF pathway reproduces several aspects of the observed scaling process. Furthermore, analysis of IGF1-treated mouse molars and computational modeling indicate that IGF signaling scales teeth by simultaneously enhancing growth and by inhibiting the cusp-patterning program, thereby providing a relatively simple mechanism for scaling teeth during development and evolution. Finally, comparative data from shrews to elephants suggest that this scaling mechanism regulates the minimum tooth size possible, as well as the patterning potential of large teeth.
当进化导致身体大小的差异时,器官通常会按比例缩放。器官和身体大小之间紧密关系的一个著名例子是哺乳动物磨牙的缩放比例。为了研究牙齿在发育和进化过程中的缩放方式,我们比较了老鼠和老鼠磨牙从起始到最终大小的发育情况。虽然老鼠磨牙的线性尺寸是老鼠磨牙的两倍,但它们的形状基本相同。在这里,我们专注于第一个下磨牙,由于其在物种内的变异性低,因此被认为是与大小相关模式的最可靠牙齿替代物。我们发现,磨牙的缩放比例很早就开始了,而且老鼠磨牙的模式形成速度与老鼠磨牙一样快,但尺寸更大。通过转录组学,我们发现,一种已知的调节身体大小的胰岛素样生长因子 1(IGF1)在老鼠磨牙中的表达水平明显高于老鼠磨牙。离体和体内老鼠模型表明,IGF 途径的调节可以再现观察到的缩放过程的几个方面。此外,对 IGF1 处理的老鼠磨牙的分析和计算模型表明,IGF 信号通过同时增强生长和抑制尖峰模式形成程序来缩放牙齿,从而为发育和进化过程中的牙齿缩放提供了相对简单的机制。最后,来自鼩鼱到大象的比较数据表明,这种缩放机制调节了最小可能的牙齿尺寸以及大牙齿的模式形成潜力。
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