title: Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis.
abstract: ICAT, inhibitor of beta-catenin and T cell factor, or Ctnnbip1, is a negative regulator of the Wnt signaling pathway that interferes with the interaction between beta-catenin and T cell factor. Some ICAT-deficient (ICAT-/-) embryos exhibit unilateral or bilateral renal agenesis. In this study, we investigated developmental processes in the ICAT-/- kidney. ICAT was highly expressed in both the ureteric bud (UB) and the surrounding metanephric mesenchymal (MM) cells in the metanephros of embryonic day E11.5-E13.5 wild-type (ICAT+/+) mouse. In the E12.5-ICAT-/- metanephros, UB branching was delayed, and a T-shaped, bifurcated UB was frequently seen; this was never seen in the E12.5-ICAT+/+ metanephros. More apoptotic MM cells were detected in the ICAT-/- metanephros than in the ICAT+/+ metanephros. These results suggest that the loss of ICAT gene function causes the arrest of UB branching and the apoptotic death of MM cells, resulting in renal agenesis.
authors.affiliation: Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Satoh
authors.forename: Akiko
authors.initials: A
authors.lastname: Iizuka-Kogo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nomura
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
authors.forename: Takao
authors.initials: T
authors.lastname: Senda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D047108:Embryonic Development; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014513:Ureter / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*