αE-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development.

Chun-Ying Li,Hongbing Lu,Jing Lan,Wei Du,Jimmy Hu,Nicole Galicia,Ophir D Klein

doi:10.1038/ncomms12133

Abstract

Embryonic signalling centres are specialized clusters of non-proliferating cells that direct the development of many organs. However, the mechanisms that establish these essential structures in mammals are not well understood. Here we report, using the murine incisor as a model, that αE-catenin is essential for inhibiting nuclear YAP localization and cell proliferation. This function of αE-catenin is required for formation of the tooth signalling centre, the enamel knot (EK), which maintains dental mesenchymal condensation and epithelial invagination. EK formation depends primarily on the signalling function of αE-catenin through YAP and its homologue TAZ, as opposed to its adhesive function, and combined deletion of Yap and Taz rescues the EK defects caused by loss of αE-catenin. These findings point to a developmental mechanism by which αE-catenin restricts YAP/TAZ activity to establish a group of non-dividing and specialized cells that constitute a signalling centre.

Highlights

Embryonic signalling centres are specialized clusters of non-proliferating cells that direct the development of many organs
The enamel knot (EK) is comprised of a group of post-mitotic cells, in contrast to the surrounding epithelium, where active proliferation takes place to support the continuous growth of the tissue[5]
Shh, Bmp[4] and Fgf[3], which are expressed in the molar EK24–26, are expressed in the incisor EK at this stage, providing us additional markers to assess for the presence of these cells (Fig. 1h,j)

Summary

Introduction

Embryonic signalling centres are specialized clusters of non-proliferating cells that direct the development of many organs. We report, using the murine incisor as a model, that aE-catenin is essential for inhibiting nuclear YAP localization and cell proliferation This function of aE-catenin is required for formation of the tooth signalling centre, the enamel knot (EK), which maintains dental mesenchymal condensation and epithelial invagination. EK formation depends primarily on the signalling function of aE-catenin through YAP and its homologue TAZ, as opposed to its adhesive function, and combined deletion of Yap and Taz rescues the EK defects caused by loss of aE-catenin These findings point to a developmental mechanism by which aE-catenin restricts YAP/TAZ activity to establish a group of non-dividing and specialized cells that constitute a signalling centre. The mechanisms by which aE-catenin regulates tissue morphogenesis remain incompletely understood

Methods

Results

Conclusion