Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis
Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis
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DOI：
10.1016/j.bbrc.2007.08.085
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发表时间：
2007-11-03
影响因子：
3.1
通讯作者：
Senda, Takao
中科院分区：
文献类型：
--
作者：
Hasegawa, Yoshimi;Satoh, Kiyotoshi;Senda, Takao
ICAT，β-连环蛋白和T细胞因子的抑制剂，或CtnnbipI，是Wnt信号通路的负调节剂，其干扰β-连环蛋白和T细胞因子之间的相互作用。一些ICAT缺陷（ICAT（-/-））胚胎表现出单侧或双侧肾发育不全。在这项研究中，我们研究了ICAT-/-肾的发育过程。ICAT在胚胎E11.5-E13.5野生型（ICAT（+/+））小鼠后肾的输尿管芽（UB）和周围的后肾间充质（MM）细胞中高度表达。在E12.5-ICAT（-/-）后肾中，UB分支延迟，经常可见T形分叉UB;这在E12.5-ICAT（+/+）后肾中从未见过。在ICAT-/-后肾中比在ICAT+/+后肾中检测到更多的凋亡MM细胞。这些结果表明，ICAT基因功能的丧失导致UB分支的停滞和MM细胞的凋亡性死亡，从而导致肾发育不全。(C)2007爱思唯尔公司All rights reserved.
ICAT, inhibitor of (beta-catenin and T cell factor, or CtnnbipI, 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. (C) 2007 Elsevier Inc. All rights reserved.