Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition
Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition
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DOI：
10.1073/pnas.0910086106
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发表时间：
2009-12-29
影响因子：
11.1
通讯作者：
Viriot, Laurent
中科院分区：
文献类型：
--
作者：
Charles, Cyril;Lazzari, Vincent;Viriot, Laurent
进化生物学的一个核心挑战是理解基因突变如何成为形态变化的基础。由于高度钙化的牙釉质能够保存详细的牙齿特征，研究牙齿形态使这个问题能够在灭绝和现存物种中得到解决。先前的研究发现，突变小鼠的牙齿形态可能有严重的异常，几位作者已经探索了突变小鼠牙齿数量变化的进化意义。然而，尽管它们可以潜在地揭示进化机制，但牙齿形状的异常仍然研究得很少。在这里，我们报告说，Fgf3基因的剂量的改变引起形态学的变化，在基因工程突变小鼠和人类患者。通过将携带Fgf3突变的小鼠和人类的牙齿形态与原始啮齿动物和灵长类动物化石进行比较，我们确定Fgf3剂量的减少会导致类似于祖先形态逐渐重现的表型。我们建议，在FGF信号通路的修改中发挥了重要作用，在哺乳动物牙列的进化，产生新的尖和相互连接的尖由新的波峰。我们预计，我们的多学科研究将推进各种哺乳动物谱系中微妙的牙齿修饰与基因突变的详细相关性。
A central challenge in evolutionary biology is understanding how genetic mutations underlie morphological changes. Because highly calcified enamel enables preservation of detailed dental features, studying tooth morphology enables this question to be addressed in both extinct and extant species. Previous studies have found that mutant mice can have severe abnormalities in tooth morphology, and several authors have explored the evolutionary implications of tooth number modifications in mutants. However, although they can potentially shed much light on evolutionary mechanisms, anomalies in tooth shape remain poorly studied. Here, we report that alterations in dosage of the Fgf3 gene cause morphological changes in both genetically engineered mutant mice and in human patients. By comparing the dental morphologies in mice and humans carrying Fgf3 mutations with primitive rodent and primate fossils, we determined that decreases in dosage of Fgf3 lead to phenotypes that resemble the progressive reappearance of ancestral morphologies. We propose that modifications in the FGF signaling pathway have played an important role in evolution of mammalian dentition by giving rise to new cusps and interconnecting cusps by new crests. We anticipate that our multidisciplinary study will advance the detailed correlation of subtle dental modifications with genetic mutations in a variety of mammalian lineages.