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First published online 24 November 2005
doi: 10.1242/dev.02175

Development 133, 173-180 (2006)
Published by The Company of Biologists 2006
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Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development

Xiuqin Zhang1, Thaddeus S. Stappenbeck2, Andrew C. White1, Kory J. Lavine1, Jeffrey I. Gordon1,3 and David M. Ornitz1,*

1 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
2 Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
3 The Center for Genome Sciences, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.

* Author for correspondence (e-mail: dornitz{at}wustl.edu)

Accepted 24 October 2005

Fibroblast growth factor (FGF) signaling mediates reciprocal mesenchymal-epithelial cell interactions in the developing mouse lung and limb. In the gastrointestinal (GI) tract, FGF10 is expressed in the cecal mesenchyme and signals to an epithelial splice form of FGF receptor (FGFR) 2 to regulate epithelial budding. Here, we identify FGF9 as a reciprocal epithelial-mesenchymal signal required for cecal morphogenesis. Fgf9 null (Fgf9-/-) mouse embryos have agenesis of the embryonic cecum, lacking both mesenchymal expansion and an epithelial bud. In the cecal region of Fgf9-/- embryos, mesenchymal expression of Fgf10 and Bmp4 is notably absent, whereas the expression of epithelial markers, such as sonic hedgehog, is not affected. Using epithelial and whole explant cultures, we show that FGF9 signals to mesenchymal FGFRs and that FGF10 signals to epithelial FGFRs. Taken together, these data show that an epithelial FGF9 signal is necessary for the expansion of cecal mesenchyme and the expression of mesenchymal genes that are required for epithelial budding. Thus, these data add to our understanding of FGF-mediated reciprocal epithelial-mesenchymal signaling.

Key words: Fibroblast growth factor 9 (FGF9), FGF10, Gut development, Cecum, Budding morphogenesis, Epithelial-mesenchymal cross-talk


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