From snapshots to movies: Understanding early tooth development in four dimensions

Abstract

The developing tooth offers a model for the study of ectodermal appendage organogenesis. The signaling networks that regulate tooth development have been intensively investigated, but how cell biological responses to signaling pathways regulate dental morphogenesis remains an open question. The increasing use of ex vivo imaging techniques has enabled live tracking of cell behaviors over time in high resolution. While recent studies using these techniques have improved our understanding of tooth morphogenesis, important gaps remain that require additional investigation. In addition, some discrepancies have arisen between recent studies, and resolving these will advance our knowledge of tooth development.

Tissue Mechanical Forces and Evolutionary Developmental Changes Act Through Space and Time to Shape Tooth Morphology and Function

“…Mice have only incisors and molars, and do not develop canines and premolars; in mouse molars, the dental epithelium originates from a group of Fgf8 ‐expressing oral epithelial cells arranged as a large rosette‐like structure (100–200 μm in diameter) in the proximal mandible at embryonic day 11.5 (E11.5) . Once released from the rosette, dental epithelial progenitors move anteriorly toward a Shh ‐expressing signaling center, where they contribute to the thickening epithelial tissue known as the molar placode shortly after E11.5 (Figure ) . Local thickening of the dental epithelium results from cell divisions at the placodal field and the ensuing generation of stratified suprabasal cells .…”

“…[11] Once released from the rosette, dental epithelial progenitors move anteriorly toward a Shhexpressing signaling center, where they contribute to the thickening epithelial tissue known as the molar placode shortly after E11.5 (Figure 1). [1,4] Local thickening of the dental epithelium results from cell divisions at the placodal field and the ensuing generation of stratified suprabasal cells. [17] This process is, in part, regulated by FGFsignaling; chemical inhibition of the FGFpathway impedes cell proliferation and subsequent stratification of the molar tooth germ.…”

“…The tooth is an excellent model system to study this topic because of its simple structure, ease of manipulation, and clinical relevance. Research over the past few decades using the mouse molar, which is similar to human rooted teeth and easily cultured ex vivo, has yielded key insights into the signaling pathways and genetic changes required for correct dental development . More recently, the continuously growing rodent incisor has emerged as a model to study adult stem cells and their role in homeostasis and repair of a fully grown organ .…”

“…Research over the past few decades using the mouse molar, which is similar to human rooted teeth and easily cultured ex vivo, has yielded key insights into the signaling pathways and genetic changes required for correct dental development. [1][2][3][4][5] More recently, the continuously growing rodent incisor has emerged as a model to study adult stem cells and their role in homeostasis and repair of a fully grown organ. [6][7][8] Results from these studies have provided the basic framework to develop stem-cell-based strategies for regenerative medicine, as human teeth cannot regenerate enamel, the outermost protective layer of the tooth, due to the loss of epithelial stem cells after tooth eruption.…”

Effective Differentiation of Induced Pluripotent Stem Cells Into Dental Cells

“…Tooth morphogenesis and differentiation is regulated by the interaction between epithelium and mesenchyme (Kim et al, ). Therefore, in mice, strategies in recapitulating tooth organ formation have fixated on the recombination of epithelium and mesenchyme at selected stages of development, in which tooth forming capacity exists and is optimized (Duailibi et al, ; Nakao et al, ; Yamamoto et al, ).…”