Sox9 and Nkx2.5 Determine the Pyloric Sphincter Epithelium Under the Control of BMP Signaling

The organs of the digestive tract are specified by coordinated signaling between the endoderm and mesoderm during development. These epithelial-mesenchymal interactions lead to the organ-specific morphogenesis and differentiation of regions along the gut tube. In this paper, we show that in the chick, the SRY-related transcription factor Sox9 is a marker for the posterior gizzard. Viral misexpression of Sox9 in the gizzard mesoderm is sufficient to specify epithelium characteristic of the pyloric sphincter. Sox9 expression is normally limited to the region of the posterior gizzard under the regulation of BMP signaling from the adjacent midgut. Misexpression of an activated form of BMPR1b in the gizzard upregulates Sox9 expression, while the BMP antagonist noggin down-regulates Sox9 expression in the gizzard mesoderm. Previously, Nkx2.5 was identified as a marker for the mesoderm of the pyloric sphincter. As with Sox9, BMP signaling appears to regulate Nkx2.5 and its ability to determine the pyloric epithelium. Despite these similarities, our evidence suggests that Sox9 and Nkx2.5 are regulated independently by BMP signaling, and act coordinately to specify the pyloric sphincter.