Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells

• DOI: 10.1242/dev.070763
• Publication Date: 2011-12-22T01:51:25Z
• Authors: Kelli L. VanDussen; Alexis J. Carulli; Theresa M. Keeley; Sanjeevkumar R. P...; Brent J. Puthoff; Scott T. Magness; Ivy T. Tran; Ivan Maillard; Christian Siebel; Åsa Kolterud; Ann S. Grosse; Deborah L. Gumucio; Stephen A. Ernst; Yu-Hwai Tsai; Peter J. Dempsey; Linda C. Samuelson
• Keywords: HES1; Cell fate determination; Paneth cell; Notch proteins

Notch signaling is known to regulate the proliferation and differentiation of intestinal stem progenitor cells; however, direct cellular targets specific functions signals had not been identified. We show here in mice that directly crypt base columnar (CBC) cell maintain activity. inhibition induced rapid CBC loss, with reduced proliferation, apoptotic death efficiency organoid initiation. Furthermore, expression cell-specific marker Olfm4 was dependent on signaling, transcription activated through RBP-Jκ binding sites promoter. also led precocious epithelial progenitors into secretory types, including large numbers cells expressed both Paneth goblet markers. Analysis function Atoh1-deficient intestine demonstrated changes were Atoh1, whereas regulation gene Atoh1 independent. Our findings suggest distinct populations adult fate choice control homeostasis.