Structure and expression of a novel frizzled gene isolated from the developing mouse gut.

The Wnt/APC (adenomatous polyposis coli)/beta-catenin pathway plays a central role in the pathogenesis of colorectal cancer and probably also in normal development of the gastrointestinal tract. Frizzled proteins function as cell-surface receptors for the Wnt family of extracellular ligands. Many components of the Wnt signalling pathway are expressed widely, and determinants of tissue-specific functions are poorly understood. A better understanding of how Wnt signalling regulates tissue-specific development and gut epithelial homoeostasis requires characterization of the many components of this signalling pathway. We therefore wished to identify frizzled genes with limited tissue distribution of expression and isolated Mfz10, a novel member of the mouse family of frizzled genes, from the developing fetal gut. Highest levels of Mfz10 mRNA are detected throughout late embryonic development, in the brain, heart, lung and digestive tract. In adult mice Mfz10 mRNA is detected at highest levels in the heart, brain and lung. Expression in the adult gastrointestinal tract is much weaker, with higher levels in foregut derivatives (oesophagus and stomach) compared with regions derived from the fetal midgut and hindgut; particularly strong mRNA expression is observed in the squamous epithelium of the oesophagus. The amino acid sequence of Mfz10 is nearly identical to that of human FzE2 (also known as FzD2). Interestingly, mRNA levels of human FzD2 are reported to be up-regulated in oesophageal squamous cell carcinomas. These findings suggest a likely role for Mfz10 in the developing and adult foregut.