The oral cavity of vertebrates is generally thought to arise as an ectodermal invagination. 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 pulp. Yet in many vertebrate groups, teeth are not restricted only to the oral cavity, 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 slits. However, when the oropharyngeal membrane, which forms a sharp ecto/endodermal border, 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' or 'inside-out' influx of the epithelium.
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