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Dual epithelial origin of vertebrate oral teeth


The oral cavity of vertebrates is generally thought to arise as an ectodermal invagination1,2. Consistent with this, oral teeth are proposed to arise exclusively from ectoderm, contributing to tooth enamel epithelium, and from neural crest derived mesenchyme, contributing to dentin and pulp3,4,5. Yet in many vertebrate groups, teeth are not restricted only to the oral cavity6,7,8,9, but extend posteriorly as pharyngeal teeth that could be derived either directly from the endodermal epithelium, or from the ectodermal epithelium that reached this location through the mouth or through the pharyngeal slits6. However, when the oropharyngeal membrane, which forms a sharp ecto/endodermal border10, is broken, the fate of these cells is poorly known. Here, using transgenic axolotls with a combination of fate-mapping approaches, we present reliable evidence of oral teeth derived from both the ectoderm and endoderm and, moreover, demonstrate teeth with a mixed ecto/endodermal origin. Despite the enamel epithelia having a different embryonic source, oral teeth in the axolotl display striking developmental uniformities and are otherwise identical. This suggests a dominant role for the neural crest mesenchyme over epithelia in tooth initiation and, from an evolutionary point of view, that an essential factor in teeth evolution was the odontogenic capacity of neural crest cells, regardless of possible ‘outside-in’11 or ‘inside-out’12 influx of the epithelium.

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Figure 1: Ectoderm contribution to mouth and tooth formation in the Mexican axolotl.
Figure 2: Endoderm contribution to tooth formation.
Figure 3: Germ-layer origin and morphogenesis of teeth of the Mexican axolotl.
Figure 4: A quantitative screening of teeth from different tooth fields with respect to their germ-layer origin.


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We wish to thank E. Tanaka and H. Andreas for supplying us with GFP axolotl embryos, L. Mchedlishvili for technical advice and O. Sebesta for help with confocal microscopy. We are grateful to M. Bronner–Fraser, R. Ericsson, D. Meulemans Medeiros, L. Olsson, P. D. Polly, D. W. Stock and A. Tucker for comments on the manuscript. Grants from the Ministry of Youth, Education and Sport of the Czech Republic (MSMT 0021620828), SMWK (Dresden) and COST Action B23 ‘Oral facial development and regeneration’ are gratefully acknowledged.

Author Contributions Tissue grafting was carried out in the laboratory of H.-H.E., who also helped with initial experiments. V.S. made transplantations and performed sectioning and image analyses as his Master’s thesis under the supervision of R.C., who also designed the initial experiments and wrote the manuscript. R.C. and I.H. planned the study and interpreted the results, I.H. made statistical analyses and helped in writing the manuscript, and all authors discussed the results and commented on the manuscript.

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Correspondence to Robert Cerny.

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Supplementary Information 1

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Supplementary Video 1

This file contains a Supplementary Video file showing a stack of optic deconvoluted layers through 20 µm thick cryostat section from an embryo after receiving both GFP ECT graft and DiI END injection. (AVI 6669 kb)

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Soukup, V., Epperlein, HH., Horácek, I. et al. Dual epithelial origin of vertebrate oral teeth. Nature 455, 795–798 (2008).

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