Wnt signaling in the mouse small intestine

Wnt signaling is essential for maintaining the intestinal epithelium, promoting stem cell renewal while preventing excessive proliferation. Although 19 Wnt ligands exist in humans and mice, their individual roles in the intestine remain unclear. This work characterizes canonical Wnt‑activated cells in the adult intestine and examines interactions with non‑canonical ligands. Wnt‑reporter activity was confined to stem‑cell–rich crypt bases, largely excluding transient‑amplifying cells, and expanded following γ‑irradiation. Overexpression of WNT1 increased proliferation and induced polyp formation, underscoring the need for tight pathway control. Conversely, ectopic expression of the non‑canonical ligand Wnt5a inhibited canonical signaling and altered Paneth cell localization. Together, these findings highlight distinct ligand‑specific functions and reveal regulatory feedback mechanisms that shape intestinal homeostasis and regeneration.