Most mammals have two sets of teeth (diphyodont) - a deciduous dentition replaced by a permanent dentition; however, the mouse possesses only one tooth generation (monophyodont). In diphyodonts, the replacement tooth forms on the lingual side of the first tooth from the successional dental lamina. This lamina expresses the stem/progenitor marker Sox2 and has activated Wnt/β-catenin signalling at its tip. Although the mouse does not replace its teeth, a transient rudimentary successional dental lamina (RSDL) still forms during development. The mouse RSDL houses Sox2-positive cells, but no Wnt/β-catenin signalling. Here, we show that stabilising Wnt/β-catenin signalling in the RSDL in the mouse leads to proliferation of the RSDL and formation of lingually positioned teeth. Although Sox2 has been shown to repress Wnt activity, overexpression of Wnts leads to a downregulation of Sox2, suggesting a negative-feedback loop in the tooth. In the mouse, the first tooth represses the formation of the replacement, and isolation of the RSDL is sufficient to induce formation of a new tooth germ. Our data highlight key mechanisms that may have influenced the evolution of replacement teeth.This article has an associated 'The people behind the papers' interview.

Centre for Craniofacial and Regenerative Biology Department of Craniofacial Development and Stem Cell Biology King's College London London SE1 9RT UK

Centre for Craniofacial and Regenerative Biology Department of Craniofacial Development and Stem Cell Biology King's College London London SE1 9RT UK Department of Developmental Biology Institute of Experimental Medicine Czech Academy of Sciences 142 20 Prague Czech Republic

Institute of Animal Physiology and Genetics Czech Academy of Sciences 602 00 Brno Czech Republic Department of Experimental Biology Faculty of Science Masaryk University 625 00 Brno Czech Republic

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