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Epimorphin expression in intestinal myofibroblasts induces epithelial morphogenesis.

Christine Fritsch1, Elzbieta A Swietlicki, Olivier Lefebvre

  • 1Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

The Journal of Clinical Investigation
|December 5, 2002
PubMed
Summary

Mesenchymal epimorphin is crucial for developing the gut

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Area of Science:

  • Developmental Biology
  • Gastroenterology
  • Cell Biology

Background:

  • Gut development relies on endoderm-mesenchyme interactions.
  • Epimorphin, a mesenchymal protein, is present during fetal gut development.

Purpose of the Study:

  • To investigate the role of epimorphin in gut ontogeny and crypt-villus axis formation.

Main Methods:

  • Transfected rat intestinal myofibroblasts with epimorphin cDNA (sense and antisense).
  • Cocultured myofibroblasts with Caco2 intestinal cells.
  • Implanted rat gut endoderm with transfected myofibroblasts into chick embryos.

Main Results:

  • Epimorphin overexpression in myofibroblasts induced Caco2 cells to form compact clusters.
  • In vivo grafts with epimorphin overexpression showed well-formed villi and crypts.
  • Epimorphin increased bone morphogenetic protein 4 (Bmp4) expression, and noggin partially blocked its effects.

Conclusions:

  • Mesenchymal epimorphin is essential for proper crypt-villus morphogenesis.
  • Epimorphin's effects are mediated by secreted factors, including Bmp4.