Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development
Xiuqin Zhang1, Thaddeus S Stappenbeck, Andrew C White
1Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
Development (Cambridge, England)
|November 26, 2005
Summary
Fibroblast growth factor 9 (FGF9) is essential for embryonic cecum development. FGF9 signals from the epithelium to mesenchyme, promoting growth and gene expression necessary for proper GI tract formation.
Area of Science:
- Developmental biology
- Gastroenterology
- Cell signaling
Background:
- Fibroblast growth factor (FGF) signaling is crucial for organ development, mediating interactions between epithelial and mesenchymal cells.
- In the gastrointestinal (GI) tract, FGF10 from mesenchyme signals to epithelial FGF receptor 2 (FGFR2) to regulate epithelial budding.
- The precise signaling pathways governing cecal morphogenesis are not fully understood.
Purpose of the Study:
- To identify novel FGF signaling pathways involved in embryonic cecal development.
- To elucidate the roles of FGF9 and FGF10 in reciprocal epithelial-mesenchymal communication during cecum morphogenesis.
- To determine the necessity of FGF9 for cecal formation and associated gene expression.
Main Methods:
- Analysis of Fgf9 null (Fgf9(-/-)) mouse embryos to assess cecal development.
- Examination of gene expression patterns for FGF ligands, receptors, and developmental markers in wild-type and Fgf9(-/-) embryos.
- In vitro studies using epithelial and whole explant cultures to investigate FGF signaling pathways.
Main Results:
- Fgf9(-/-) mouse embryos exhibit agenesis of the embryonic cecum, with a complete lack of mesenchymal expansion and epithelial bud formation.
- Mesenchymal expression of Fgf10 and Bmp4 is significantly reduced or absent in Fgf9(-/-) embryos.
- Epithelial markers like sonic hedgehog remain unaffected in Fgf9(-/-) embryos, indicating specific defects in mesenchymal signaling.
- Experiments confirmed that FGF9 signals to mesenchymal FGFRs, while FGF10 signals to epithelial FGFRs.
Conclusions:
- Epithelial-derived FGF9 is a critical signal required for the expansion of cecal mesenchyme during embryonic development.
- FGF9 signaling is necessary for inducing the expression of mesenchymal genes essential for epithelial budding and cecal morphogenesis.
- These findings reveal a reciprocal FGF signaling loop, with FGF9 from epithelium and FGF10 from mesenchyme, essential for GI tract development.
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