Bone morphogenic protein (BMP) signaling promotes normal crypt-villus differentiation, and expression of the BMP antagonists noggin (Nog) (Haramis et al., 2004) or gremlin 1 (Grem1) (Davis et al., 2015) in all intestinal cells via the villin-1 (Vil1) promoter blocks differentiation and induces tumor formation, with ectopic (Box 1) proliferative crypts forming on villi perpendicular to the normal crypt plane. Here, GREM1 is linked to neoplasm.