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First published online April 13, 2005
doi: 10.1242/10.1242/dev.01808
1 Department of Molecular and Cellular Biology, Baylor College of Medicine,
Houston, TX 77030, USA
2 Department of Cell Biology and Neurosciences, University of South Alabama,
Mobile, AL 36688, USA
3 Department of Cell and Developmental Biology, Vanderbilt University Medical
Center, Nashville, TN 37232,USA
4 Developmental Biological Program, Baylor College of Medicine, Houston, TX
77030, USA
* Authors for correspondence (e-mail: stsai{at}bcm.tmc.edu; mtsai{at}bcm.tmc.edu)
Accepted 1 March 2005
COUP-TFII, an orphan member of the steroid receptor superfamily, has been implicated in mesenchymal-epithelial interaction during organogenesis. The generation of a lacZ knock-in allele in the COUP-TFII locus in mice allows us to use X-gal staining to follow the expression of COUP-TFII in the developing stomach. We found COUP-TFII is expressed in the mesenchyme and the epithelium of the developing stomach. Conditional ablation of floxed COUP-TFII by Nkx3-2Cre recombinase in the gastric mesenchyme results in dysmorphogenesis of the developing stomach manifested by major patterning defects in posteriorization and radial patterning. The epithelial outgrowth, the expansion of the circular smooth muscle layer and enteric neurons as well as the posteriorization of the stomach resemble phenotypes exhibited by inhibition of hedgehog signaling pathways. Using organ cultures and cyclopamine treatment, we showed downregulation of COUP-TFII level in the stomach, suggesting COUP-TFII as a target of hedgehog signaling in the stomach. Our results are consistent with a functional link between hedgehog proteins and COUP-TFII, factors that are vital for epithelial-mesenchymal interactions.
Key words: Nuclear orphan receptor, Sonic hedgehog, Organogenesis, Stomach, Mouse, Nr2f1, Nr2f2
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