title: Notch signaling promotes the generation of EphrinB1-positive intestinal epithelial cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biological Sciences, Seoul National University, Silim-dong, Gwanak-gu, Seoul, South Korea.
authors.forename: Bon-Kyoung
authors.initials: BK
authors.lastname: Koo
authors.forename: Hyoung-Soo
authors.initials: HS
authors.lastname: Lim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Yoon
authors.forename: Yongwook
authors.initials: Y
authors.lastname: Choi
authors.forename: Myung-Phil
authors.initials: MP
authors.lastname: Kong
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kong