Antagonistic interaction between Ezh2 and Arid1a coordinates root patterning and development via Cdkn2a in mouse molars

Elife. 2019 Jul 1:8:e46426. doi: 10.7554/eLife.46426.

Abstract

Patterning is a critical step during organogenesis and is closely associated with the physiological function of organs. Tooth root shapes are finely tuned to provide precise occlusal support to facilitate the function of each tooth type. However, the mechanism regulating tooth root patterning and development is largely unknown. In this study, we provide the first in vivo evidence demonstrating that Ezh2 in the dental mesenchyme determines patterning and furcation formation during dental root development in mouse molars. Mechanistically, an antagonistic interaction between epigenetic regulators Ezh2 and Arid1a controls Cdkn2a expression in the dental mesenchyme to regulate dental root patterning and development. These findings indicate the importance of balanced epigenetic regulation in determining the tooth root pattern and the integration of roots with the jaw bones to achieve physiological function. Collectively, our study provides important clues about the regulation of organogenesis and has general implications for tooth regeneration in the future.

Keywords: Arid1a; Ezh2; developmental biology; epigenetic regulation; mouse; root patterning.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alveolar Process / embryology
  • Alveolar Process / metabolism
  • Animals
  • Body Patterning*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelium / embryology
  • Epithelium / metabolism
  • Furcation Defects / pathology
  • Histones / metabolism
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Methylation
  • Mice, Transgenic
  • Molar / embryology*
  • Odontoblasts / metabolism
  • Periodontal Ligament / embryology
  • Periodontal Ligament / metabolism
  • Tooth Root / embryology*
  • Transcription Factors / metabolism*

Substances

  • Arid1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • Histones
  • Transcription Factors
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse

Associated data

  • GEO/GSE131684