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Publication : Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition.

First Author  Charles C Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  52 Pages  22364-8
PubMed ID  20018768 Mgi Jnum  J:156450
Mgi Id  MGI:4420688 Doi  10.1073/pnas.0910086106
Citation  Charles C, et al. (2009) Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition. Proc Natl Acad Sci U S A 106(52):22364-8
abstractText  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.
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