Anomalous incisor morphology indicates tissue-specific roles for Tfap2a and Tfap2b in tooth development

Abstract

Mice possess two types of teeth that differ in their cusp patterns; incisors have one cusp and molars have multiple cusps. The patterning of these two types of teeth relies on fine-tuning of the reciprocal molecular signaling between dental epithelial and mesenchymal tissues during embryonic development. Here we show that the incisors are populated only at early time points by the neural crest, whereas the molars continue to receive contributions at later stages, revealing a temporal difference that could alter epithelial-mesenchymal signaling dynamics between these two types of teeth. The AP-2 transcription factors, particularly Tfap2a and Tfap2b, are essential components of such epithelial-mesenchymal signaling interactions that coordinate craniofacial development in mice and other mammals, but little is known about their roles in the regulation of tooth development and shape. We demonstrate that incisors and molars differ in their temporal and spatial expression of Tfap2a and Tfap2b; in particular, at the bud stage, Tfap2a is expressed in both the epithelium and mesenchyme of the incisors and molars but expression of Tfap2b is restricted to the mesenchyme of the molars. Tissue-specific deletions show that loss of the epithelial domain of Tfap2a and Tfap2b affects the number and spatial arrangement of the incisors, notably resulting in duplicated lower incisors. In contrast, deletion of these two genes in the mesenchymal domain has little effect on tooth development. Collectively these results implicate epithelial expression of Tfap2a and Tfap2b in dorsal-ventral patterning of the incisors and suggest that these genes contribute to morphological differences between anterior (incisor) and posterior (molar) teeth within the mammalian dentition. HighlightsO_LILate-migrating cranial neural crest cells contribute extensively to the developing molar tooth germs but minimally to the incisors. C_LIO_LIDuring tooth development, transcription factors Tfap2a and Tfap2b are expressed in spatially and temporally dynamic patterns and differ between incisor and molar tooth germs. C_LIO_LIEpithelial expression of Tfap2a and Tfap2b is necessary for incisor development, but mesenchymal expression of these genes is not required. C_LI