Ror2-mediated non-canonical Wnt signaling regulates Cdc42 and cell proliferation during tooth root development

Development. 2021 Jan 21;148(2):dev196360. doi: 10.1242/dev.196360.


The control of size and shape is an important part of regulatory process during organogenesis. Tooth formation is a highly complex process that fine-tunes the size and shape of the tooth, which are crucial for its physiological functions. Each tooth consists of a crown and one or more roots. Despite comprehensive knowledge of the mechanism that regulates early tooth crown development, we have limited understanding of the mechanism regulating root patterning and size during development. Here, we show that Ror2-mediated non-canonical Wnt signaling in the dental mesenchyme plays a crucial role in cell proliferation, and thereby regulates root development size in mouse molars. Furthermore, Cdc42 acts as a potential downstream mediator of Ror2 signaling in root formation. Importantly, activation of Cdc42 can restore cell proliferation and partially rescue the root development size defects in Ror2 mutant mice. Collectively, our findings provide novel insights into the function of Ror2-mediated non-canonical Wnt signaling in regulating tooth morphogenesis, and suggest potential avenues for dental tissue engineering.

Keywords: Cdc42; Cell proliferation; Ror2; Tooth root.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Female
  • Male
  • Mesoderm / embryology
  • Mice
  • Mice, Mutant Strains
  • Morphogenesis
  • Odontoblasts / cytology
  • Odontoblasts / metabolism
  • Receptor Tyrosine Kinase-like Orphan Receptors / metabolism*
  • Tooth Root / cytology
  • Tooth Root / embryology*
  • Tooth Root / metabolism*
  • Wnt Signaling Pathway*
  • cdc42 GTP-Binding Protein / metabolism*


  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Ror2 protein, mouse
  • cdc42 GTP-Binding Protein