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The response of embryonic mouse dental epithelium and mesoderm to tissues of ectopic origin was examined. Isolated molar or incisor mesoderm was confronted with epithelium isolated from the plantar surface of the embryonic mouse foot plate or from the snout. Harmoniously structured teeth were formed from the foot epithelium and incisor or molar mesoderm. These data are interpreted as an unequivocal demonstration of the inductive role of the dental mesenchyme. Teeth were absent in confrontations of dental mesenchyme and snout epithelium. The presence of hair follicles in these explants is described and discussed with reference to other integumental epithelio-mesenchymal interactions. Dental epithelium forms keratinizing surface-like epithelium and invading bands of epithelium in association with foot mesoderm; definitive structures are not formed. On the other hand, when incisor or molar epithelium is associated with snout mesoderm, hair follicles are seen in addition to keratinizing surface-like epithelial configurations. The roles of the epithelial and mesenchymal tissues and the nature of epithelio-mesenchymal interactions in the developing mouse integument are discussed.

Studies of epithelio-mesenchymal interactions during embryonic organogenesis have led to a number of conclusions regarding the nature of cellular and tissue differentiation (McLoughlin, 1963; Grobstein, 1967). For example, the importance of both the epithelium and the mesenchyme and the dependence of some systems on a limited number of specific mesenchymal tissues have been pointed out (Hilfer, 1968). Intimately connected with the analysis of the factors that elicit differentiation during such interactions is the question of structural specificity of the differentiated structure. Is the directive for the final form of the structure resident in the epithelium, in the mesoderm, or in both? Can a seemingly stable epithelium undergo transformation to a more labile state and respond to a new interaction with the result that a new epithelial structure is formed (Billingham & Silvers, 1963, 1968)?

Tooth germs grown on Eagle's medium solidified with agar will differentiate in vitro. Normal development was suppressed by beta-2-thienylalanine (1 or 2 millimols per liter), but it proceeded when phenylalanine and beta-2-thienylalanine were present in equimolar concentrations. This effect may have been due to interference with protein metabolism in the dermal papillar cells.

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