Six2 activity is required for the formation of the mammalian pyloric sphincter.

The functional activity of Six2, a member of the so/Six family of homeodomain-containing transcription factors, is required during mammalian kidney organogenesis. We have now determined that Six2 activity is also necessary for the formation of the pyloric sphincter, the functional gate at the stomach-duodenum junction that inhibits duodenogastric reflux. Our data reveal that several genes known to be important for pyloric sphincter formation in the chick (e.g., Bmp4, Bmpr1b, Nkx2.5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals. Thus, we propose that Six2 activity regulates this gene network during the genesis of the pyloric sphincter in the mouse.