关于脊椎动物牙齿演化的经典观点是所谓的“由外向内”（outside-in）模型，即口腔的空腔和口腔中的牙齿都是通过内陷作用从外胚层形成的。现在，对转基因蝾螈所做的一项研究表明，这个过程要比上述模型所描述的更为复杂。
对胚胎中细胞的命运所做分析显示，口腔中的牙齿既来自外胚层，又来自内胚层：它们中有些甚至同时起源于外胚层和内胚层。这说明，神经冠间充质相对于上皮细胞在牙齿形成中起主导作用。这一发现在演化上的意义是，神经冠细胞的牙齿形成能力是牙齿演化的必要因素，而不管上皮细胞是经过了一个由外向内还是由内向外的过程。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 455, 795-798 (9 October 2008) | doi:10.1038/nature07304
Dual epithelial origin of vertebrate oral teeth
Vladimír Soukup1, Hans-Henning Epperlein2, Ivan Horácek1 & Robert Cerny1
Department of Zoology, Charles University in Prague, Vinicna 7, 128 44 Prague, Czech Republic
Department of Anatomy, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany
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.
