The Role of Gli3 Transcription Factor in the Developing Mouse Stomach

The Sonic hedgehog (Shh) signaling pathway plays a critical role in murine gastric development. When Shh is knocked out in the mouse embryonic stomach, glandular epithelial hyperplasia occurs. Furthermore, this phenotype was mimicked in Gli3−/−, but not Gli2−/− stomachs. I utilized three additional mouse models that modulate Gli3 activity to better understand the role of Gli3 in the developing stomach - the Gli3Δ699/Δ699 ,Gli3P1−4/P1−4, and Kif7−/− mice. The Gli3P1−4/P1−4 stomach displayed glandular epithelial overgrowth, as did the Kif7−/− stomach to a lesser extent; the Gli3Δ699/Δ699 stomach displayed glandular hypoplasia. Moreover, the Gli3P1−4/P1−4 and Kif7−/− stomachs have a thicker circular smooth muscle, and the Gli3Δ699/Δ699 had a thinner one relative to wild-type. It appears that altering the balance of Gli3 in favour of its activator results in gastric glandular epithelial and circular smooth muscle hyperplasia, and a balance favouring the Gli3 repressor results in hypoplasia.MAS