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

Cyril Charles, Vincent Lazzari, Paul Tafforeau, Thomas Schimmang, Mustafa Tekin, Ophir Klein, Laurent Viriot

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)22364-22368
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 19 2009


  • Dental morphology
  • Muroidea
  • Primates

ASJC Scopus subject areas

  • General


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