The developmental basis for scaling of mammalian tooth size.

The developmental basis for scaling of mammalian tooth size.
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DOI:
10.1073/pnas.2300374120
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发表时间:
2023-06-20
影响因子:
11.1
通讯作者:
Jernvall, Jukka
Jernvall, Jukka
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Christensen, Mona M.;Hallikas, Outi;Das Roy, Rishi;Vaananen, Vilma;Stenberg, Otto E.;Hakkinen, Teemu J.;Francois, Jean-Christophe;Asher, Robert J.;Klein, Ophir D.;Holzenberger, Martin;Jernvall, Jukka

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尽管众所周知哺乳动物的牙齿会随着体型进化,但牙齿大小比例变化的发育基础仍知之甚少。因为仅大小不同而形状不变的器官对于大小比例变化具有启示意义,我们比较了小鼠和大鼠的臼齿发育。在此,我们表明大小差异是逐渐出现的,在牙齿发育的敏感模式形成期之前就已开始。基因表达、实验以及计算机模拟显示,胰岛素样生长因子(IGF)信号传导在不干扰形状的情况下调节牙齿大小。这种形状不变的大小比例变化是通过对生长和模式形成基因的反向调节实现的,从而为器官大小比例变化提供了一种机制。从鼩鼱到大象的数据表明这种大小比例变化机制具有保守性,并且大牙齿的模式形成潜力增加。 当进化导致体型差异时,器官通常也会相应地按比例变化。器官与体型之间紧密关系的一个著名例子是哺乳动物臼齿的大小比例变化。为了研究牙齿在发育和进化过程中是如何按比例变化的,我们比较了小鼠和大鼠从牙齿开始发育到最终大小的臼齿发育过程。大鼠臼齿的线性尺寸是小鼠臼齿的两倍,但其形状大体相同。在此,我们重点关注第一下臼齿,由于其在物种内的变异性较低,它被认为是与大小相关模式最可靠的牙齿代表。我们发现臼齿的大小比例变化开始得较早,并且大鼠臼齿的模式形成速度与小鼠臼齿相同,但尺寸更大。通过转录组学,我们发现一种已知的体型调节因子——胰岛素样生长因子1(Igf1)在大鼠臼齿中的表达高于小鼠臼齿。体外和体内小鼠模型表明,IGF通路的调节重现了所观察到的大小比例变化过程的多个方面。此外,对IGF1处理的小鼠臼齿的分析以及计算机模拟表明,IGF信号传导通过同时促进生长和抑制牙尖模式形成程序来调节牙齿大小,从而为发育和进化过程中牙齿的大小比例变化提供了一种相对简单的机制。最后,从鼩鼱到大象的比较数据表明,这种大小比例变化机制调节着可能的最小牙齿尺寸以及大牙齿的模式形成潜力。
Although mammalian teeth are well known to evolve with body size, the developmental basis for tooth scaling remains poorly understood. Because organs differing only in size but not in shape are informative about scaling, we compared molar development of the mouse and the rat. Here, we show that size differences emerge gradually, beginning before the sensitive patterning period of tooth development. Gene expressions, experiments, and computational modeling reveal that insulin-like growth factor (IGF) signaling scales tooth size without perturbing the shape. This shape-invariant scaling is achieved by inverse regulation of growth and patterning genes, thereby providing a mechanism for organ scaling. Data from shrews to elephants suggest conservation of the scaling mechanism and increased patterning potential in large teeth. 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 (Igf1), 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.
DOI: 10.1002/jez.b.23009
发表时间: 2021-01
期刊: Journal of experimental zoology. Part B, Molecular and developmental evolution
影响因子: --
作者:
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