Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis.
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.
Hasegawa
Yoshimi
Y
Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
Satoh
Kiyotoshi
K
Iizuka-Kogo
Akiko
A
Shimomura
Atsushi
A
Nomura
Ryuji
R
Akiyama
Tetsu
T
Senda
Takao
T
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*