title: Organized emergence of multiple-generations of teeth in snakes is dysregulated by activation of Wnt/beta-catenin signalling.
abstract: In contrast to mammals, most reptiles constantly regenerate their teeth. In the snake, the epithelial dental lamina ends in a successional lamina, which proliferates and elongates forming multiple tooth generations, all linked by a permanent dental lamina. To investigate the mechanisms used to control the initiation of new tooth germs in an ordered sequential pattern we utilized the polyphodont (multiple-generation) corn snake (Pantherophis guttatus). We observed that the dental lamina expressed the transcription factor Sox2, a multipotent stem cell marker, whereas the successional lamina cells expressed the transcription factor Lef1, a Wnt/β-catenin pathway target gene. Activation of the Wnt/β-catenin pathway in culture increased the number of developing tooth germs, in comparison to control untreated cultures. These additional tooth germs budded off from ectopic positions along the dental lamina, rather than in an ordered sequence from the successional lamina. Wnt/β-catenin activation enhanced cell proliferation, particularly in normally non-odontogenic regions of the dental lamina, which widely expressed Lef1, restricting the Sox2 domain. This suggests an expansion of the successional lamina at the expense of the dental lamina. Activation of the Wnt/β-catenin pathway in cultured snake dental organs, therefore, led to changes in proliferation and to the molecular pattern of the dental lamina, resulting in loss of the organised emergence of tooth germs. These results suggest that epithelial compartments are critical for the arrangement of organs that develop in sequence, and highlight the role of Wnt/β-catenin signalling in such processes.
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London, United Kingdom ; Department of Anatomy, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marcia
authors.initials: M
authors.lastname: Gaete
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Tucker
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D012911:Snakes / Q000254:growth & development*; D014070:Tooth / Q000254:growth & development*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D051153:Wnt Proteins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
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