Notch signals control the fate of immature progenitor cells in the intestine

Abstract

Notch genes encode a range of membrane receptors that regulate cell-fate decisions by influencing communication between adjacent cells. Two groups now report the involvement of Notch signals in controlling the fate of intestinal epithelial tissue. In addition, blockade of the Notch pathway with the γ-secretase inhibitor DBZ halted growth of adenomas (polyps) in the small intestine and colon. Various γ-secretase inhibitors are being developed for the treatment of Alzheimer's disease; this new work suggests that they might also be used to treat colorectal cancers. The Notch signalling pathway plays a crucial role in specifying cellular fates in metazoan development by regulating communication between adjacent cells1,2. Correlative studies suggested an involvement of Notch in intestinal development. Here, by modulating Notch activity in the mouse intestine, we directly implicate Notch signals in intestinal cell lineage specification. We also show that Notch activation is capable of amplifying the intestinal progenitor pool while inhibiting cell differentiation. We conclude that Notch activity is required for the maintenance of proliferating crypt cells in the intestinal epithelium.