Notch Signaling Promotes the Generation of EphrinB1-Positive Intestinal Epithelial Cells
- Title
- Notch Signaling Promotes the Generation of EphrinB1-Positive Intestinal Epithelial Cells
- Authors
- KOO, BK; LIM, HS; CHANG, HJ; YOON, MJ; CHOI, Y; KONG, MP; KIM, CH; KIM, JM; PARK, JG; KONG, YY; null
- Date Issued
- 2009-07
- Publisher
- W B SAUNDERS CO-ELSEVIER INC
- Abstract
- BACKGROUND & AIMS: The intestinal epithelium consists of EphB2-positive proliferative basal cryptic cells and Ephrin B1-positive, postmitotic differentiated cells. We investigated the effects of Notch signaling on formation of the EphB2-EphrinB1 boundary using Mouse and tissue culture models. METHODS: We created mice in which Mind bomb-1 (Mib1), an essential E3 ubiquitin ligase that activates Notch ligands, was inactivated specifically in the intestinal epithelia (Vil-Cre
Mib1(f/f))
Notch is, therefore, inactivated in this tissue. We also studied the effects of different inhibitors on intestinal epithelial cells (IEC-6) that express activated Notch. Tissues and cells were analyzed by immunohistochemical and immunoblot analyses. RESULTS: The intestinal epithelia of Vil-Cre
Mib1(f/f) mice had reduced numbers of EphrinB1-positive cells, compared with controls, but increases in EphB2-positive cells
beta-catenin was activated in these cells. These phenotypes were reversed by expression of a constitutively active form of Notch1. In the IEC-6 cells, Notch signaling activated the expression of EphrinB1 in an Hes1-independent manner, but down-regulated the expression of EphB2 through the GSK3 beta-mediated inhibition of beta-catenin. CONCLUSIONS: Notch signaling regulates formation of the EphB2-EphrinB1 boundary in the mouse intestinal epithelium.
- Keywords
- GLYCOGEN-SYNTHASE KINASE-3; GAMMA-SECRETASE INHIBITOR; PROGENITOR CELLS; BETA-CATENIN; MIND BOMB-1; DIFFERENTIATION; LINEAGE; LIGAND; CANCER; FATE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28298
- DOI
- 10.1053/J.GASTRO.200
- ISSN
- 0016-5085
- Article Type
- Article
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