Notch signaling promotes the generation of EphrinB1-positive intestinal epithelial cells
Gastroenterology, 2009•Elsevier
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; Mib1f/f); Notch is, therefore, inactivated in this tissue. We also …
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; Mib1f/f); Notch is, therefore, inactivated in this tissue. We also …
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;Mib1f/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;Mib1f/f mice had reduced numbers of EphrinB1-positive cells, compared with controls, but increases in EphB2-positive cells; β-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 GSK3β-mediated inhibition of β-catenin.
CONCLUSIONS
Notch signaling regulates formation of the EphB2–EphrinB1 boundary in the mouse intestinal epithelium.
Elsevier