The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells

PLoS One. 2013 Oct 8;8(10):e75106. doi: 10.1371/journal.pone.0075106. eCollection 2013.

Abstract

During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1α+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Claudins / genetics
  • Claudins / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Occludin / genetics
  • Occludin / metabolism
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Claudins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Occludin
  • Zonula Occludens-1 Protein
  • radixin
  • claudin 6

Grants and funding

This work was supported by Grants-in Aid for the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Naito Foundation, and the Uehara Memorial Foundation. K.S. received the research fellowship for young scientists from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.