New perspectives on tooth development and the dental stem cell niche

Adult stem cells have the capacity to self-renew and differentiate along multiple lineages in addition to contributing to ongoing tissue maintenance and regeneration after injury. They reside in specific locations called stem cell niches. In biology of the tooth, the discovery of dental epithelial stem cells in continuously growing teeth has been a recent breakthrough. The niche for the adult stem cells of these teeth is formed at the region of the apical end in tooth development. The region possesses a commonly specialized histological structure for the maintenance of adult stem cells and the production of various progenitor cells producing dental tissues. The molecular signals regulating the maintenance and cell fate decision of adult stem cells, such as Notch1, Lunatic fringe, fibroblast growth factor (FGF)-10, are expressed in the epithelial structure and the surrounding mesenchyme. Based on histological and molecular biological studies, we propose a new concept that the eternal tooth buds producing various dental progeny are formed at the apical end in the development of continuously growing teeth, and coin a new term of "apical bud" for indicating this specialized epithelial structure. Furthermore, the relationship between signaling centers and the expression of FGF-10 mRNA as the determinant of morphogenesis is discussed with an emphasis on tooth and limb development, taking note that the expression pattern of FGF-10 is an important key for understanding the mechanisms for the diversity of cusp patterns and between continuous and limited growth.