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Gastroenterology. 2009 Jul;137(1):145-55, 155.e1-3. doi: 10.1053/j.gastro.2009.03.046. Epub 2009 Mar 28.

Notch signaling promotes the generation of EphrinB1-positive intestinal epithelial cells.

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1
Department of Biological Sciences, Seoul National University, Silim-dong, Gwanak-gu, Seoul, South Korea.

Abstract

BACKGROUND & AIMS:

The intestinal epithelium consists of EphB2-positive proliferative basal cryptic cells and EphrinB1-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 GSK3beta-mediated inhibition of beta-catenin.

CONCLUSIONS:

Notch signaling regulates formation of the EphB2-EphrinB1 boundary in the mouse intestinal epithelium.

PMID:
19332065
DOI:
10.1053/j.gastro.2009.03.046
[Indexed for MEDLINE]
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