Direct regulation of intestinal fate by Notch

BZ Stanger, R Datar, LC Murtaugh… - Proceedings of the …, 2005 - National Acad Sciences
BZ Stanger, R Datar, LC Murtaugh, DA Melton
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
The signals that maintain the proper balance between adult intestinal cell types are poorly
understood. Loss-of-function studies have implicated the Notch pathway in the regulation of
intestinal fate during development. However, it is unknown whether Notch has a role in
maintaining the balance of different cell types in the adult intestine and whether it acts
reversibly. To determine whether Notch has a direct effect on intestinal development and
adult intestinal cell turnover, we have used a gain-of-function approach to activate Notch …
The signals that maintain the proper balance between adult intestinal cell types are poorly understood. Loss-of-function studies have implicated the Notch pathway in the regulation of intestinal fate during development. However, it is unknown whether Notch has a role in maintaining the balance of different cell types in the adult intestine and whether it acts reversibly. To determine whether Notch has a direct effect on intestinal development and adult intestinal cell turnover, we have used a gain-of-function approach to activate Notch. Ectopic Notch signaling in adult intestinal progenitor cells leads to a bias against secretory fates, whereas ectopic Notch activation in the embryonic foregut results in reversible defects in villus morphogenesis and loss of the proliferative progenitor compartment. We conclude that Notch regulates adult intestinal development by controlling the balance between secretory and absorptive cell types. In the embryo, Notch activation perturbs morphogenesis, possibly through effects on stem or progenitor cells.
National Acad Sciences