Figure 2.

Transcription factor domains in the development of the gastric region. Representation of the mouse developing posterior foregut at (A) approximately E10 and at (B) approximately E13. (A and B) Color codes correspond to specific transcription factor signatures in panel C. The future forestomach and esophagus (green) expresses Sox2, but not other glandular markers such as Gata4 and Pdx1. The future corpus (blue) expresses Sox2 and Gata4, but not the more posterior regional markers such as Pdx1. The future antrum (red) expresses Sox2, Gata4, and Pdx1, but not the intestinal marker Cdx2. The future anterior small intestine expresses Cdx2, Gata4, and Pdx1, but not the anterior endodermal marker Sox2. The anterior boundary of Gata4 (blue/green border) is expressed in the glandular stomach but not the forestomach (green). (D) Speculative model of glandular stomach specification during development. Based on developmental studies, early foregut progenitors express the important transcription factors of the FoxA family, Sox17, and Gata4/6. Around this time, an appropriate balance of WNT, FGF, and RA signaling is needed to specify the region of the gut that gives rise to gastric progenitors. These pathways actively posteriorize the endoderm—too little or too much signaling could drive the endoderm to a more anterior or posterior fate, respectively. Future gastric progenitors need to acquire Sox2 expression and not the intestine determinant Cdx2, which is expressed in more posterior endoderm. Once organ budding begins, local mesenchymal signals are crucial to enforce glandular identity and repress adjacent nonglandular stomach organ fates such as the esophagus/forestomach and intestine. Potentially, these signals act through driving expression of potential gastric specification transcription factors such as Gata4 and Hnf1β.