title: Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition.
abstract: 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.
authors.affiliation: Department of Orofacial Sciences , University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0442, USA.
authors.forename: Cyril
authors.initials: C
authors.lastname: Charles
authors.forename: Vincent
authors.initials: V
authors.lastname: Lazzari
authors.forename: Paul
authors.initials: P
authors.lastname: Tafforeau
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimmang
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.forename: Ophir
authors.initials: O
authors.lastname: Klein
authors.forename: Laurent
authors.initials: L
authors.lastname: Viriot
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D051518:Fibroblast Growth Factor 3 / Q000172:deficiency / Q000235:genetics*; D005580:Fossils; D016368:Frameshift Mutation; D018628:Gene Dosage; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D018345:Mice, Knockout; D009115:Muridae / Q000235:genetics; D009154:Mutation; D009805:Odontogenesis / Q000235:genetics*; D010641:Phenotype; D011323:Primates / Q000235:genetics; D013045:Species Specificity; D014070:Tooth / Q000033:anatomy & histology; D014071:Tooth Abnormalities / Q000235:genetics
chemical_list: C496444:FGF3 protein, human; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3