Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations

PLoS One. 2016 Sep 2;11(9):e0161336. doi: 10.1371/journal.pone.0161336. eCollection 2016.


The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses.

MeSH terms

  • Animals
  • Cell Division / physiology
  • Cell Movement / physiology
  • Cell Shape / physiology
  • Epithelium / growth & development*
  • Mice
  • Microscopy, Confocal / methods
  • Models, Biological
  • Odontogenesis / physiology*
  • Tooth / growth & development*

Grants and funding

This work was partially funded by a Grant-in-Aid for Scientific Research on Innovative Areas (No. 2311152) to TT and Organ Technologies Inc. This work was performed under an Invention Agreement between Tokyo University of Science, RIKEN and Organ Technologies Inc. TT is a director at Organ Technologies Inc. The specific role of this author is articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.