Myosin II mediates Shh signals to shape dental epithelia via control of cell adhesion and movement

PLoS Genet. 2024 Jun 10;20(6):e1011326. doi: 10.1371/journal.pgen.1011326. eCollection 2024 Jun.

Abstract

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination.

MeSH terms

  • Animals
  • Cell Adhesion* / genetics
  • Cell Movement* / genetics
  • Epithelial Cells / metabolism
  • Epithelium / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins* / genetics
  • Hedgehog Proteins* / metabolism
  • Mice
  • Morphogenesis / genetics
  • Myosin Type II* / genetics
  • Myosin Type II* / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Tooth / growth & development
  • Tooth / metabolism

Substances

  • Hedgehog Proteins
  • Myosin Type II
  • Shh protein, mouse
  • Proto-Oncogene Proteins c-akt